127. Development of a Kinetic ELISA (kELISA) and Reactive B-cell Frequency (RBF) Assay to Detect Respiratory Syncytial Virus (RSV) Pre-Fusion F Protein-Specific Immune Responses in Infants

Abstract Background RSV is a major cause of pediatric respiratory disease. Antibodies to the prefusion conformation of the RSV fusion (pre-F) protein are needed for virus neutralization. Methods We measured RSV-specific responses in two groups of children < 3 years of age; subjects with laboratory-confirmed RSV (RSV-infected) or infants born in the period May to September and enrolled prior to their first RSV season (RSV-uninfected). RSV-infected infants had blood samples obtained at 1, 6, 9, and 12 months after infection. RSV-uninfected infants had blood samples obtained at enrollment, at the end of their first RSV season, and 6 months later. A kELISA to measure RSV pre-F-specific antibodies and an RBF assay to identify RSV F-specific B cells were developed. Results 102 subjects were enrolled; 11 were excluded due to missed visits or withdrawal. Of the 65 subjects in the RSV-uninfected group, all were kELISA positive at enrollment, consistent with maternal antibody transfer. 53 subjects had sufficient samples for analysis at multiple time points; 29 became seronegative and 24 remained seropositive. In the seronegative group, the kELISA value decreased rapidly to < 0.25 by 6 months after the RSV season in 27/29 (93%), (Figure 1a). In the persistently seropositive group, all 24 subjects maintained a positive kELISA value, with some developing higher values over time, consistent with asymptomatic infection (Figure 1b). An RBF assay was used to determine whether antibodies were due to persistent maternal antibodies or endogenous production (Figure 2). In the seronegative group, 24/29 (80%) had a negative RBF; in the seropositive group, 23/24 (96%) had a positive RBF during follow-up. There were 26 subjects in the RSV-infected group; 22 had sufficient samples for analysis at multiple time points. All were seropositive by kELISA at one month post-infection with variable kELISA values during follow-up (Figure 3). 17/22 (77%) had a positive RBF, although 4 of the subjects without a positive RBF had indeterminate results at ≥ 1 visit. Figure 1. kELISA values of baseline RSV-negative subjects, by subject age at time of sample. Panel A: Subjects classified as seronegative (n=29). Panel B: Subjects without known RSV classified as persistently seropositive (n=24). Figure 2. Reactive B-cell frequency assay. The first step in the RBF assay is growth of Lymphoblastoid Cell Lines (LCLs), as shown over days 1-3 (Left-Day 1, Middle-Day 2, Right-Day 3, magnification 200X). The cells circled in the figure indicate a single LCL’s growth over time. LCL supernatant is used to detect RSV F-protein specific antibodies using traditional ELISA, resulting in a positive, indeterminate, or negative result. Indeterminate results occur due to a lack of cell viability and/or failure to form LCLs, resulting in failure to exceed an optical density of 5x background. Figure 3. kELISA values of RSV-infected subjects, by subject age at time of sample. First sample was obtained at approximately one month after laboratory-confirmed RSV. Conclusion Assays measuring F-specific immune responses in infants will be critical for RSV vaccine development. A kELISA targeting RSV pre-F epitopes, with an RBF assay targeting RSV F-specific B cells, may allow discrimination for maternal and infant-derived antibodies. Disclosures Isaac Thomsen, MD, MSCI, Horizon Therapeutics (Individual(s) Involved: Self): Consultant James E. Crowe, Jr., MD, Astra Zeneca (Grant/Research Support)IDBiologics (Board Member, Grant/Research Support, Shareholder)Luna Biologics (Consultant)Meissa Vaccines (Advisor or Review Panel member)Takeda Vaccines (Grant/Research Support) Kathryn M. Edwards, MD, Bionet (Individual(s) Involved: Self): Consultant; CDC (Individual(s) Involved: Self): Research Grant or Support; IBM (Individual(s) Involved: Self): Consultant; Merck (Individual(s) Involved: Self): member DSMC, Other Financial or Material Support; Moderna (Individual(s) Involved: Self): member DSMC, Other Financial or Material Support; NIH (Individual(s) Involved: Self): Research Grant or Support; Pfizer (Individual(s) Involved: Self): member DSMC, Other Financial or Material Support; Roche (Individual(s) Involved: Self): member of DSMB, Other Financial or Material Support; Sanofi Pasteur (Individual(s) Involved: Self): member DSMB, Other Financial or Material Support; Sequiras (Individual(s) Involved: Self): Member DSMB, Other Financial or Material Support; X4 Pharmaceuticals (Individual(s) Involved: Self): Consultant Buddy Creech, MD, MPH, Altimmune (Consultant)Astellas (Other Financial or Material Support, Data and Safety Monitoring Committee)Diotheris (Consultant)GSK (Consultant)Horizon (Consultant)Merck (Scientific Research Study Investigator)Premier Healthcare (Advisor or Review Panel member)Vir (Consultant)

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1104. Risk Factors and Outcomes of Refractory and/or Resistant Cytomegalovirus (CMV) Infection after Allogeneic Hematopoietic Stem Cell Transplantation

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1290 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S582-S583

Author(s):

Eleni Karantoni ◽

Yiqi Su ◽

Anat Stern ◽

Phaedon D Zavras ◽

Sergio Giralt ◽

...

Keyword(s):

Risk Factors ◽

Overall Survival ◽

T Cell ◽

Panel Member ◽

Multivariable Model ◽

Research Support ◽

Review Panel ◽

Material Support ◽

Advisory Boards ◽

Research Grant

Abstract Background The epidemiology of CMV end-organ disease (EOD) after Hematopoietic Cell Transplant (HCT) in the era of preemptive therapy (PET) is defined. In contrast, less data exists on refractory and/or resistant (R/R) CMV. We report on 1) the incidence; 2) risk factors and outcomes of R/R CMV by 1-year post HCT. Methods Retrospective review of 167 CMV seropositive (R+) recipients of first marrow or peripheral blood HCT from 1/2014 - 12/2017 managed by PET. Refractory CMV was defined as failure to achieve >1 log10 decrease in CMV viral load (VL) and having VL >1,000 IU/mL after ≥14 day of PET. Resistant CMV required genotypic confirmation of resistance mutation(s) in UL54 and/or UL97 genes. End organ disease (EOD) was defined by standard criteria. Patients (pts) were followed through 1-year post HCT and were categorized in two mutually exclusive groups as R/R and no R/R. Demographics, clinical characteristics and outcomes were extracted from medical records and hospital databases. Univariable and multivariable logistic models were used to identify risk factors for R/R CMV. Results Of 167 PET recipients, 91 (54.5%) received ex vivo T cell depleted (TCD) HCT; 40 (24.0%) had mismatched donor; and 26 (15.6%) had multiple myeloma. 66/167 (39.5%) pts developed refractory CMV (6 pts also had resistant CMV). Time from HCT to CMV viremia was shorter in R/R group: median (IQR) 21.5 (17.2-27.8) days compared to no R/R group: 26 (19-32) days (p=0.031). Maximum VL was higher for R/R compared to no R/R: median (IQR) 9,118 (2,849-18,456) and 868 (474-1,908), respectively (p< 0.001). In multivariable model, risk factors for R/R included TCD HCT (p< 0.0001) and higher VL at PET initiation (p=0.0002). In contrast, CMV seropositive donor (p=0.035) was protective (Figure 1). CMV EOD developed in 28.2% of R/R and 16.2% of no R/R groups (p=0.085) (Figure 2). Overall survival at 1 year was 59.1% for R/R compared to 83.1% for no R/R group (p=0.00027) (Figure 3). Figure 1. Adjusted odds ratio (OR) and 95% confidence interval (CI) from multivariable model evaluating risk factors of refractory/resistant (R/R) CMV. Figure 2. Cumulative incidence curves of CMV end-organ disease (EOD) at 1-year post HCT Figure 3. Kaplan-Meier survival curves of overall survival (OS) at 1-year post HCT Conclusion 1) Refractory and/or resistant CMV occurred in 39,5% of PET recipients. 2) T-cell depletion and higher CMV VL at PET initiation were risk factors for R/R CMV in multivariable models. 3) R/R CMV was associated with more EOD and worse overall survival. Disclosures Sergio Giralt, MD, Amgen (Advisor or Review Panel member, Research Grant or Support, Served an advisory board for Amgen, Actinuum, Celgene, Johnson & Johnson, JAZZ pharmaceutical, Takeda, Novartis, KITE, and Spectrum pharma and has received research support from Amgen, Actinuum, Celgene, Johnson & Johnson, and Miltenyi, Takeda.) Miguel-Angel Perales, MD, Abbvie (Other Financial or Material Support, Honoraria from Abbvie, Bellicum, Celgene, Bristol-Myers Squibb, Incyte, Merck, Novartis, Nektar Therapeutics, Omeros, and Takeda.)ASTCT (Other Financial or Material Support, Volunteer member of the Board of Directors of American Society for Transplantation and Cellular Therapy (ASTCT), Be The Match (National Marrow Donor Program, NMDP), and the CIBMTR Cellular Immunotherapy Data Resource (CIDR) Committee)Cidara Therapeutics (Advisor or Review Panel member, Other Financial or Material Support, Serve on DSMBs for Cidara Therapeutics, Servier and Medigene, and the scientific advisory boards of MolMed and NexImmune.)Kite/Gilead (Research Grant or Support, Other Financial or Material Support, Received research support for clinical trials from Incyte, Kite/Gilead and Miltenyi Biotec.) Genovefa Papanicolaou, MD, Chimerix (Research Grant or Support)Merck&Co (Research Grant or Support, Investigator and received funding and consulting fees from Merck, Chimerix, Shire and Astellas)

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1178. Sustained Vaccine Effectiveness Against Influenza-Associated Hospitalization in Children: Evidence from the New Vaccine Surveillance Network, 2015-2016 Through 2019-2020

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.1371 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S681-S682

Author(s):

Leila C Sahni ◽

Eric A Naioti ◽

Samantha M Olson ◽

Angela P Campbell ◽

Marian G Michaels ◽

...

Keyword(s):

Influenza Vaccine ◽

Research Study ◽

Scientific Research ◽

Panel Member ◽

Onset Date ◽

Research Support ◽

Review Panel ◽

Material Support ◽

Study Investigator ◽

Research Grant

Abstract Background Adult studies have demonstrated intra-season declines in influenza vaccine effectiveness (VE) with increasing time since vaccination; however, data in children are limited. Methods We conducted a prospective, test-negative study of children ages 6 months through 17 years hospitalized with acute respiratory illness at 7 pediatric medical centers each season in the New Vaccine Surveillance Network during the 2015-2016 through 2019-2020 influenza seasons. Cases were children with an influenza-positive molecular test; controls were influenza-negative children. Controls were matched to cases by illness onset date using 3:1 nearest neighbor matching. We estimated VE [100% x (1 – odds ratio)] by comparing the odds of receipt of ≥ 1 dose of influenza vaccine ≥ 14 days before the onset of illness that resulted in hospitalization among influenza-positive children to influenza-negative children. Changes in VE over time between vaccination date and illness onset date during each season were estimated using multivariable logistic regression models. Results Of 8,430 hospitalized children (4,781 [57%] male; median age 2.4 years), 4,653 (55%) received ≥ 1 dose of influenza vaccine. On average, 48% and 85% of children were vaccinated by the end of October and December, respectively. Influenza-positive cases (n=1,000; 12%) were less likely to be vaccinated than influenza-negative controls (39% vs. 61%, p< 0.001) and overall VE against hospitalization was 53% (95% CI: 46%, 60%). Pooling data across 5 seasons, the odds of any influenza-associated hospitalization increased 0.96% (95% CI: -0.76%, 2.71%) per week with a corresponding weekly decrease in VE of 0.45% (p=0.275). Odds of hospitalization with time since vaccination increased 0.66% (95% CI: -0.76%, 2.71%) per week in children ≤ 8 years (n=3,084) and 2.16% (95% CI: -1.68%, 6.15%) per week in children 9-17 years (n=771). No significant differences were observed by virus subtype or lineage. Figure 1. Declines in influenza VE over time from 2015-2016 through 2019-2020, overall (a) and by age group (b: ≤ 8 years; c: 9-17 years) Conclusion We observed minimal intra-season declines in VE against influenza-associated hospitalization in U.S. children. Vaccination following Advisory Committee on Immunization Practices guidelines and current timing of vaccine receipt is the best strategy for prevention of influenza-associated hospitalization in children. Disclosures Marian G. Michaels, MD, MPH, Viracor (Grant/Research Support, performs assay for research study no financial support) John V. Williams, MD, GlaxoSmithKline (Advisor or Review Panel member, Independent Data Monitoring Committee)Quidel (Advisor or Review Panel member, Scientific Advisory Board) Elizabeth P. Schlaudecker, MD, MPH, Pfizer (Grant/Research Support)Sanofi Pasteur (Advisor or Review Panel member) Natasha B. Halasa, MD, MPH, Genentech (Other Financial or Material Support, I receive an honorarium for lectures - it’s a education grant, supported by genetech)Quidel (Grant/Research Support, Other Financial or Material Support, Donation of supplies/kits)Sanofi (Grant/Research Support, Other Financial or Material Support, HAI/NAI testing) Natasha B. Halasa, MD, MPH, Genentech (Individual(s) Involved: Self): I receive an honorarium for lectures - it’s a education grant, supported by genetech, Other Financial or Material Support, Other Financial or Material Support; Sanofi (Individual(s) Involved: Self): Grant/Research Support, Research Grant or Support Janet A. Englund, MD, AstraZeneca (Consultant, Grant/Research Support)GlaxoSmithKline (Research Grant or Support)Meissa Vaccines (Consultant)Pfizer (Research Grant or Support)Sanofi Pasteur (Consultant)Teva Pharmaceuticals (Consultant) Christopher J. Harrison, MD, GSK (Grant/Research Support)Merck (Grant/Research Support)Pfizer (Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support) Flor M. Munoz, MD, Biocryst (Scientific Research Study Investigator)Gilead (Scientific Research Study Investigator)Meissa (Other Financial or Material Support, DSMB)Moderna (Scientific Research Study Investigator, Other Financial or Material Support, DSMB)Pfizer (Scientific Research Study Investigator, Other Financial or Material Support, DSMB)Virometix (Other Financial or Material Support, DSMB)

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639. Time to Recurrence of Clostridioides difficile Infection (rCDI) is Rapid Following Completion of Standard of Care Antibiotics: Results from ECOSPOR-III, a Phase 3 Double-Blind, Placebo-Controlled Randomized Trial of SER-109, an Investigational Microbiome Therapeutic

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.836 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S422-S422

Author(s):

Thomas J Louie ◽

Matthew Sims ◽

Richard Nathan ◽

Steven O'Marro ◽

Princy N Kumar ◽

...

Keyword(s):

Panel Member ◽

Standard Of Care ◽

Oral Microbiome ◽

Research Support ◽

Independent Contractor ◽

Review Panel ◽

Material Support ◽

Time To Recurrence ◽

Study Population

Abstract Background The natural history of CDI recurrence after antibiotics may be helpful to understand the window of opportunity for microbiome repair. ECOSPOR III evaluated the efficacy of SER-109, an investigational microbiome therapeutic, compared to placebo with rates of rCDI as the primary endpoint. SER-109 was superior to placebo in reducing the rate of rCDI following standard-of-care antibiotics at 8 weeks (12.4% vs 39.8%, respectively; P < 0.001). Herein, we describe results from the secondary endpoint, time to recurrence, in this well-characterized study population. Methods A total of 182 C. difficile toxin+ adults with ≥ 3 CDI episodes and symptom resolution on CDI antibiotics were randomly assigned to SER-109 (4 capsules orally x 3 days) or placebo. Recurrence for this analysis was defined as ≥ 3 unformed stools/day for ≥ 48 hours, ± C. difficile stool toxin test, and an investigator decision to treat. Time to CDI recurrence was analyzed using observed data and Kaplan-Meier methods. Data were not imputed for subjects lost to follow-up or discontinued from study. Subjects who did not have a CDI recurrence were censored on the date of study completion, study discontinuation or death. Results Through 24 weeks, 11/89 (12.4%) SER-109 and 36/93 (38.7%) placebo subjects had rCDI (P < 0.001). Of all recurrence events in the study population, 16/47 (34.0%) were observed within 1 week; 30/47 (63.8%) within 2 weeks; and 34/47 (72.3%) within 4 weeks after randomization, highlighting the rapid onset of recurrence. On the other hand, 12/47 (25.5%) recurrences occurred between 4 and 12 weeks, highlighting late onset of recurrence in a subset of patients (Table). Significantly lower rates of recurrence in patients on SER-109 compared to placebo was maintained throughout the 24-week follow-up (Figure). Time of rCDI K-M Plot Conclusion SER-109, an investigational oral microbiome therapeutic, maintained significant efficacy in reducing rCDI vs placebo through 24 weeks. About two-thirds of all recurrences occurred within 14 days of antibiotic completion highlighting the need for rapid repair of the disrupted microbiome. However, the significant number of late recurrences in the placebo arm also highlights that rCDI trials limited to 4 weeks of follow-up after treatment completion may underestimate recurrences. Disclosures Thomas J. Louie, MD, Artugen (Advisor or Review Panel member)Crestone (Consultant, Grant/Research Support)Da Volterra (Advisor or Review Panel member)Finch Therapeutics (Grant/Research Support, Advisor or Review Panel member)MGB Biopharma (Grant/Research Support, Advisor or Review Panel member)Rebiotix (Consultant, Grant/Research Support)Seres Therapeutics (Consultant, Grant/Research Support)Summit PLC (Grant/Research Support)Vedanta (Grant/Research Support, Advisor or Review Panel member) Matthew Sims, MD, PhD, Astra Zeneca (Independent Contractor)Diasorin Molecular (Independent Contractor)Epigenomics Inc (Independent Contractor)Finch (Independent Contractor)Genentech (Independent Contractor)Janssen Pharmaceuticals NV (Independent Contractor)Kinevant Sciences gmBH (Independent Contractor)Leonard-Meron Biosciences (Independent Contractor)Merck and Co (Independent Contractor)OpGen (Independent Contractor)Prenosis (Independent Contractor)Regeneron Pharmaceuticals Inc (Independent Contractor)Seres Therapeutics Inc (Independent Contractor)Shire (Independent Contractor)Summit Therapeutics (Independent Contractor) Richard Nathan, DO, none (Other Financial or Material Support, I am PI on several clinical trials. If you need that information, I would be happy to supply it.) Princy N. Kumar, MD, AMGEN (Other Financial or Material Support, Honoraria)Eli Lilly (Grant/Research Support)Gilead (Grant/Research Support, Shareholder, Other Financial or Material Support, Honoraria)GSK (Grant/Research Support, Shareholder, Other Financial or Material Support, Honoraria)Merck & Co., Inc. (Grant/Research Support, Shareholder, Other Financial or Material Support, Honoraria) Elaine E. Wang, MD, Seres Therapeutics (Employee) Elaine E. Wang, MD, Seres Therapeutics (Employee, Shareholder) Robert Stevens, PharmD, Seres Therapeutics (Employee, Shareholder) Kelly Brady, MS, Seres Therapeutics (Employee, Shareholder) Barbara McGovern, MD, Seres Therapeutics (Employee, Shareholder) Lisa von Moltke, MD, Seres Therapeutics (Employee, Shareholder)

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154. Circulation of Rhinovirus/Enterovirus Respiratory Infections in Children During 2020-21 in the United States

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.154 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S93-S93

Author(s):

Danielle A Rankin ◽

Andrew Speaker ◽

Ariana Perez ◽

Zaid Haddadin ◽

Varvara Probst ◽

...

Keyword(s):

United States ◽

Panel Member ◽

Respiratory Viruses ◽

Research Support ◽

Review Panel ◽

Surveillance Network ◽

Material Support ◽

Percent Positivity ◽

Vaccine Surveillance ◽

Research Grant

Abstract Background Sharp declines in influenza and respiratory syncytial virus (RSV) circulation across the U.S. have been described during the pandemic in temporal association with community mitigation for control of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We aimed to determine relative frequencies of rhinovirus/enterovirus (RV/EV) and other respiratory viruses in children presenting to emergency departments or hospitalized with acute respiratory illness (ARI) prior to and during the COVID-19 pandemic. Methods We conducted a multi-center active prospective ARI surveillance study in children as part of the New Vaccine Surveillance Network (NVSN) from December 2016 through January 2021. Molecular testing for RV/EV, RSV, influenza, and other respiratory viruses [i.e., human metapneumovirus, parainfluenza virus (Types 1-4), and adenovirus] were performed on specimens collected from children enrolled children. Cumulative percent positivity of each virus type during March 2020–January 2021 was compared from March-January in the prior seasons (2017-2018, 2018-2019, 2019-2020) using Pearson’s chi-squared. Data are provisional. Results Among 69,403 eligible children, 37,676 (54%) were enrolled and tested for respiratory viruses. The number of both eligible and enrolled children declined in early 2020 (Figure 1), but 4,691 children (52% of eligible) were enrolled and tested during March 2020-January 2021. From March 2020-January 2021, the overall percentage of enrolled children with respiratory testing who had detectable RV/EV was similar compared to the same time period in 2017-2018 and 2019-2020 (Figure 1, Table 1). In contrast, the percent positivity of RSV, influenza, and other respiratory viruses combined declined compared to prior years, (p< 0.001, Figure 1, Table 1). Figure 1. Percentage of Viral Detection Among Enrolled Children Who Received Respiratory Testing, New Vaccine Surveillance Network (NVSN), United States, December 2016 – January 2021 Table 1. Percent of Respiratory Viruses Circulating in March 2020– January 2021, compared to March-January in Prior Years, New Vaccine Surveillance Network (NVSN), United States, March 2017 – January 2021 Conclusion During 2020, RV/EV continued to circulate among children receiving care for ARI despite abrupt declines in other respiratory viruses within this population. These findings warrant further studies to understand virologic, behavioral, biological, and/or environmental factors associated with this continued RV/EV circulation. Disclosures Jennifer E. Schuster, MD, Merck, Sharpe, and Dohme (Individual(s) Involved: Self): Grant/Research Support Marian G. Michaels, MD, MPH, Viracor (Grant/Research Support, performs assay for research study no financial support) John V. Williams, MD, GlaxoSmithKline (Advisor or Review Panel member, Independent Data Monitoring Committee)Quidel (Advisor or Review Panel member, Scientific Advisory Board) Elizabeth P. Schlaudecker, MD, MPH, Pfizer (Grant/Research Support)Sanofi Pasteur (Advisor or Review Panel member) Christopher J. Harrison, MD, GSK (Grant/Research Support)Merck (Grant/Research Support)Pfizer (Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support) Janet A. Englund, MD, AstraZeneca (Consultant, Grant/Research Support)GlaxoSmithKline (Research Grant or Support)Meissa Vaccines (Consultant)Pfizer (Research Grant or Support)Sanofi Pasteur (Consultant)Teva Pharmaceuticals (Consultant) Claire Midgley, PhD, Nothing to disclose Natasha B. Halasa, MD, MPH, Genentech (Other Financial or Material Support, I receive an honorarium for lectures - it’s a education grant, supported by genetech)Quidel (Grant/Research Support, Other Financial or Material Support, Donation of supplies/kits)Sanofi (Grant/Research Support, Other Financial or Material Support, HAI/NAI testing) Natasha B. Halasa, MD, MPH, Genentech (Individual(s) Involved: Self): I receive an honorarium for lectures - it’s a education grant, supported by genetech, Other Financial or Material Support, Other Financial or Material Support; Sanofi (Individual(s) Involved: Self): Grant/Research Support, Research Grant or Support

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73. Geographical Disparities in Clinical Outcomes of Severe COVID-19 Patients Treated with Remdesivir

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.383 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S167-S167

Author(s):

George Diaz ◽

Jose Ramon Arribas ◽

Philip A Robinson ◽

Anna Maria Cattelan ◽

...

Keyword(s):

Research Study ◽

Clinical Status ◽

Scientific Research ◽

Panel Member ◽

Ordinal Scale ◽

Research Support ◽

Review Panel ◽

Material Support ◽

Study Investigator ◽

Research Grant

Abstract Background Remdesivir (RDV), a RNA polymerase inhibitor with potent in vitro activity against SARS-CoV-2, is the only treatment with demonstrated efficacy in shortening the duration of COVID-19. Here we report regional differences in clinical outcomes of severe COVID-19 patients treated with RDV, as part of an open-label, randomized phase-3 trial establishing RDV treatment duration. Methods Hospitalized patients with oxygen saturation ≤94%, a positive SARS-CoV-2 PCR in the past 4 days and radiographic evidence of pneumonia were randomized 1:1 to receive 5d or 10d of intravenous RDV. We compared d14 clinical outcomes of patients from different geographical areas, as measured by mortality rates, change in clinical status from baseline (BL) on a 7-point ordinal scale and change in O2 requirements from BL. Based on previous analyses in compassionate use data showing region as an important predictor of outcome, Italy was examined separately from other regions. Results 397 patients were treated with RDV, of which 229 (58%) were in the US, 77 (19%) Italy, 61 (15% in Spain), 12 (3%) Republic of Korea, 9 (2%) Singapore, 4 (1%) Germany, 4 (1%) Hong Kong and 1 (< 1%) Taiwan. BL clinical status was worse in Italy compared to other regions (72% vs 17% requiring high-flow oxygen delivery or higher), and Italian patients were more likely to be male than patients from other regions (69% vs 63%). Overall results showed 5d RDV was as effective as 10d. Mortality at d14 was higher in Italy (18%) compared to all other countries except Italy (7%). Similarly, clinical improvement at d14, measured as ≥2-point increase in the ordinal scale, was lower in Italian patients (39%) compared to all other countries combined (64%). (Fig.1). Figure 1. Change from Baseline in Clinical Status (measured on a 7-point Ordinal Scale) at d14. Conclusion Overall, our results demonstrate significant geographical differences in the clinical course of severe COVID-19 patients treated with RDV. We observed worse outcomes, such as increased mortality and lower rate of clinical improvement, in patients from Italy compared to other regions. Disclosures George Diaz, MD, NO DISCLOSURE DATA Jose Ramon Arribas, MD, Alexa (Advisor or Review Panel member, Speaker’s Bureau, Other Financial or Material Support, Personal fees)Gilead Sciences Inc. (Scientific Research Study Investigator, Advisor or Review Panel member, Speaker’s Bureau, Other Financial or Material Support, Personal fees)Janssen (Advisor or Review Panel member, Speaker’s Bureau, Other Financial or Material Support, Personal fees)Merck (Advisor or Review Panel member, Speaker’s Bureau, Other Financial or Material Support, Personal fees)Viiv Healthcare (Advisor or Review Panel member, Speaker’s Bureau, Other Financial or Material Support, Personal fees) Jose Ramon Arribas, MD, NO DISCLOSURE DATA Philip A. Robinson, MD, NO DISCLOSURE DATA Anna Maria Cattelan, MD, NO DISCLOSURE DATA Karen T. Tashima, MD, Bristol-Myers Squibb (Research Grant or Support)Gilead Sciences Inc. (Grant/Research Support, Scientific Research Study Investigator)GlaxoSmithKline (Research Grant or Support)Merck (Research Grant or Support)Tibotec (Research Grant or Support)Viiv Healthcare (Research Grant or Support) Owen Tak-Yin Tsang, MD, Gilead Sciences Inc. (Scientific Research Study Investigator) Owen Tak-Yin Tsang, MD, NO DISCLOSURE DATA Yao-Shen Chen, MD, Gilead Sciences Inc. (Scientific Research Study Investigator) Yao-Shen Chen, MD, NO DISCLOSURE DATA Devi SenGupta, MD, Gilead Sciences Inc. (Employee, Shareholder) Elena Vendrame, MD, NO DISCLOSURE DATA Christiana Blair, MS, Gilead Sciences (Employee, Shareholder) Anand Chokkalingam, PhD, Gilead Sciences (Employee) Anu Osinusi, MD, Gilead Sciences (Employee) Diana M. Brainard, MD, Gilead Sciences (Employee) Bum Sik Chin, MD, Gilead Sciences Inc. (Scientific Research Study Investigator) Bum Sik Chin, MD, NO DISCLOSURE DATA Christoph Spinner, MD, AbbVie (Advisor or Review Panel member, Other Financial or Material Support, Travel)Bristol-Myers Squibb (Grant/Research Support, Advisor or Review Panel member, Other Financial or Material Support, Travel)Gilead Sciences Inc. (Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member, Other Financial or Material Support, Travel)Janssen (Grant/Research Support, Advisor or Review Panel member, Other Financial or Material Support, Travel)MSD (Grant/Research Support, Advisor or Review Panel member, Other Financial or Material Support, Travel)Viiv Healthcare (Grant/Research Support, Advisor or Review Panel member, Other Financial or Material Support, Travel) Gerard J. Criner, MD, Gilead Sciences Inc. (Scientific Research Study Investigator)Regeneron (Scientific Research Study Investigator) Gerard J. Criner, MD, NO DISCLOSURE DATA Jose Muñoz, MD, NO DISCLOSURE DATA David Chien Boon Lye, MD, Gilead Sciences Inc. (Scientific Research Study Investigator) David Chien Boon Lye, MD, NO DISCLOSURE DATA Robert L. Gottlieb, MD, Gilead Sciences Inc. (Scientific Research Study Investigator)

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LB13. The Efficacy and Impact in Heathy Infants of Nirsevimab on Medically Attended RSV Lower Respiratory Tract Infection

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.1649 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S811-S812

Author(s):

Laura Hammitt ◽

Ron Dagan ◽

Yuan Yuan ◽

Manuel Baca Cots ◽

...

Keyword(s):

Research Study ◽

Scientific Research ◽

Panel Member ◽

Research Support ◽

Review Panel ◽

Term Infants ◽

Study Investigator ◽

Support Research ◽

Research Grant

Abstract Background Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infection (LRTI) in infants. Nirsevimab is a single-dose monoclonal antibody with extended half-life that was shown to protect preterm infants 29 to < 35 weeks gestation against RSV LRTI. However, most medically attended (MA) cases occur in otherwise healthy, term infants for whom there is currently no effective RSV prevention strategy. We report the primary analysis of efficacy and safety, along with the impact of nirsevimab in late preterm and term infants (≥ 35 weeks gestation) in the phase 3 MELODY study (NCT03979313). Methods Infants were randomized 2:1 to receive one intramuscular injection of nirsevimab (50 mg if < 5 kg; 100 mg if ≥ 5 kg at dosing) or placebo entering their first RSV season. The primary endpoint was the incidence of MA RSV LRTI over 150 days postdose. Cases met predefined clinical criteria of disease severity and were confirmed by real-time reverse-transcriptase PCR. Safety was evaluated through 360 days postdose. Enrollment started on 23 July 2019 and was suspended following the declaration of the COVID-19 pandemic by the WHO on 11 March 2020. Results Overall, 1490 infants were randomized and included in the intent-to-treat population; 1465 (98%) completed the 150-day efficacy follow-up, and 1367 (92%) completed the 360-day safety follow-up. The incidence of MA RSV LRTI was 1.2% (n=12/994) in the nirsevimab group and 5.0% (n=25/496) in the placebo group, giving nirsevimab an efficacy of 74.5% (95% confidence interval [CI]: 49.6, 87.1; p< 0.0001). Nirsevimab averted 93.6 (95% CI 63.0, 124.0) MA LRTIs per 1000 infants dosed. Nirsevimab was well tolerated, with similar rates of adverse events (87.4% nirsevimab; 86.8% placebo) and serious adverse events (6.8% nirsevimab; 7.3% placebo) between groups. Conclusion In this phase 3 study, a single dose of nirsevimab protected late preterm and term infants against MA RSV LRTI over an RSV season with a favorable safety profile. Approximately 11 infants need to be immunized to prevent 1 case of LRTI; nirsevimab has the potential to be an important intervention to reduce the burden of RSV LRTI in healthy infants. Disclosures Laura Hammitt, MD, MedImmune (Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support)Merck & Co., Inc. (Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support)Novavax (Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support)Pfizer (Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support) Laura Hammitt, MD, MedImmune (Individual(s) Involved: Self): Grant/Research Support, Research grant to my institution; Merck (Individual(s) Involved: Self): Grant/Research Support, Research grant to my institution; Pfizer (Individual(s) Involved: Self): Grant/Research Support, Research grant to my institution Ron Dagan, MD, Medimmune/AstraZeneca (Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support)MSD (Consultant, Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member, Research Grant or Support, Speaker’s Bureau)Pfizer (Consultant, Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member, Research Grant or Support, Speaker’s Bureau) Yuan Yuan, PhD, AstraZeneca (Employee, Shareholder) Shabhir A. Mahdi, PhD, BMGF (Research Grant or Support)EDCTP (Research Grant or Support)GlaxoSmithKline (Research Grant or Support)Melody (Research Grant or Support)Minervax (Research Grant or Support)Novavax (Research Grant or Support)SAMRC (Research Grant or Support) William J. Muller, MD, PhD, Ansun (Scientific Research Study Investigator)Astellas (Scientific Research Study Investigator)AstraZeneca (Scientific Research Study Investigator)Genentech (Scientific Research Study Investigator)Gilead (Scientific Research Study Investigator)Janssen (Scientific Research Study Investigator)Karius (Scientific Research Study Investigator)Melinta (Scientific Research Study Investigator)Merck (Scientific Research Study Investigator)Nabriva (Scientific Research Study Investigator)Seqirus (Scientific Research Study Investigator)Tetraphase (Scientific Research Study Investigator) William J. Muller, MD, PhD, Ansun (Individual(s) Involved: Self): Grant/Research Support; Astellas (Individual(s) Involved: Self): Research Grant or Support; AstraZeneca (Individual(s) Involved: Self): Grant/Research Support; BD (Individual(s) Involved: Self): Research Grant or Support; Eli Lilly (Individual(s) Involved: Self): Grant/Research Support; Gilead (Individual(s) Involved: Self): Grant/Research Support; Karius, Inc. (Individual(s) Involved: Self): Grant/Research Support, Scientific Research Study Investigator; Melinta (Individual(s) Involved: Self): Grant/Research Support; Merck (Individual(s) Involved: Self): Grant/Research Support; Moderna (Individual(s) Involved: Self): Grant/Research Support; Nabriva (Individual(s) Involved: Self): Grant/Research Support; Seqirus (Individual(s) Involved: Self): Consultant; Tetraphase (Individual(s) Involved: Self): Grant/Research Support Heather J. Zar, PhD, AstraZeneca (Grant/Research Support)Novavax (Grant/Research Support)Pfizer (Grant/Research Support, Advisor or Review Panel member) Dennis Brooks, MD, AstraZeneca (Employee) Amy Grenham, MSc, AstraZeneca (Employee, Shareholder) Ulrika Wählby Hamrén, PhD, AstraZeneca R&D (Employee, Shareholder) Vaishali S. Mankad, MD, AstraZeneca (Employee) Therese Takas, BSc, AstraZeneca (Employee, Other Financial or Material Support, Own stock in AstraZeneca) Jon Heinrichs, PhD, AstraZeneca (Shareholder)Bristol Myers Squibb (Shareholder)J&J (Shareholder)Merck (Shareholder)Organon (Shareholder)Procter & Gamble (Shareholder)Sanofi (Shareholder)Sanofi Pasteur (Employee) Amanda Leach, MRCPCH, AstraZeneca (Employee, Shareholder) M. Pamela Griffin, MD, AstraZeneca (Employee) Tonya L. Villafana, PhD, AstraZeneca (Employee)

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854. Long-term Outcomes of Participants on F/TAF for Pre-Exposure Prophylaxis: Results for 144 Weeks of Follow-Up in the DISCOVER Trial

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.1049 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S517-S518

Author(s):

Moti Ramgopal ◽

Peter Ruane ◽

Yongwu Shao ◽

Ramin Ebrahimi ◽

Alex Kintu ◽

...

Keyword(s):

Research Study ◽

Scientific Research ◽

Panel Member ◽

Mineral Density ◽

Research Support ◽

Review Panel ◽

Study Investigator ◽

Research Grant

Abstract Background In DISCOVER, a multinational randomized controlled trial, F/TAF demonstrated noninferior efficacy compared to F/TDF for HIV prevention with improved bone mineral density and renal safety biomarkers at the primary endpoint (when all participants had reached 48 weeks and 50% had reached 96 weeks) and at week (W) 96, the end of the blinded phase. We now report W144 outcomes for participants who were randomized to F/TAF and continued F/TAF in the open-label extension (OLE) phase. Methods All participants who completed the randomized blinded phase could opt to receive F/TAF for at least 48 weeks in the OLE phase. We evaluated HIV incidence in participants on F/TAF through W144 and assessed changes in hip and spine bone mineral density (BMD) and in glomerular function (eGFR) from baseline to W144. Results 2,080 of the 2,694 participants initially randomized to F/TAF opted into the OLE phase, and 1,933 were still on study drug through W144, thereby leading to a total of 7,885 person-years (PY) of follow-up on F/TAF. Eight participants taking F/TAF acquired HIV in the blinded phase and 3 in the OLE phase. Dried blood spot analyses on the 3 OL infections found tenofovir diphosphate levels consistent with low adherence. Genotypic resistance testing showed no relevant resistance mutations for the 3 new infections. Among participants taking F/TAF, HIV incidence was 0.16/100 PY (95% CI 0.06-0.33) at the primary endpoint, 0.16/100 PY (95% CI 0.07-0.31) through 96 weeks and 0.14/100 PY (95% CI 0.07-0.25) through 144 weeks. Participants taking F/TAF had increases in hip BMD (mean percentage change +0.54%) and in spine BMD (mean percentage change +1.02%) from baseline to W144 (Figure 1). Median eGFR increased over 144 weeks, with a median increase of 2.6 mL/min from baseline to week 144. Participants in the F/TAF arm gained a median 2.3 kg (IQR -0.9-5.8) over 3 years of follow up. Figure 1. Changes in hip and spine bone mineral density and in eGFR through Week 144 Conclusion The OLE of DISCOVER allowed for a long-term assessment (144 wks.) of F/TAF for PrEP. HIV incidence remained low with BMD and renal function parameters remaining stable through 144 weeks of follow-up. These findings demonstrate that F/TAF is a safe and effective option for long-term use in people who would benefit from PrEP. Disclosures Moti Ramgopal, MD FACP FIDSA, Abbvie (Scientific Research Study Investigator, Speaker’s Bureau)Gilead (Consultant, Scientific Research Study Investigator, Speaker’s Bureau)Janssen (Consultant, Scientific Research Study Investigator, Research Grant or Support, Speaker’s Bureau)Merck (Consultant, Scientific Research Study Investigator)ViiV (Consultant, Scientific Research Study Investigator, Speaker’s Bureau) Peter Ruane, MD, AbbVie (Consultant, Research Grant or Support)Allergan (Research Grant or Support)Gilead Sciences Inc. (Consultant, Research Grant or Support, Shareholder, Speaker’s Bureau)Merck (Consultant, Research Grant or Support)ViiV Healthcare (Consultant, Research Grant or Support) Yongwu Shao, PhD, Gilead Sciences Inc. (Employee, Shareholder) Ramin Ebrahimi, MSc, Gilead Sciences Inc. (Employee, Shareholder) Alex Kintu, MD, ScD, Gilead Sciences Inc. (Employee, Shareholder) Christoph C. Carter, MD, Gilead Sciences Inc. (Employee, Shareholder) Moupali Das, MD, Gilead Sciences Inc. (Employee, Shareholder) Jared Baeten, MD, PHD, Gilead Sciences Inc. (Employee, Shareholder) Cynthia Brinson, MD, Abbvie (Scientific Research Study Investigator)BI (Scientific Research Study Investigator)Gilead Sciences Inc. (Scientific Research Study Investigator, Advisor or Review Panel member, Speaker’s Bureau, Personal fees)GSK (Scientific Research Study Investigator)Novo Nordisk (Scientific Research Study Investigator)ViiV Healthcare (Scientific Research Study Investigator, Advisor or Review Panel member, Speaker’s Bureau) Peter Shalit, MD, PhD, Abbvie (Grant/Research Support)Gilead Sciences (Consultant, Grant/Research Support, Speaker’s Bureau)Glaxo Smithkline (Consultant, Grant/Research Support)Janssen (Consultant, Grant/Research Support, Speaker’s Bureau)Merck (Grant/Research Support, Speaker’s Bureau)Thera (Speaker’s Bureau)ViiV Healthcare (Speaker’s Bureau) Karam Mounzer, MD, Epividian (Advisor or Review Panel member)Gilead Sciences Inc. (Consultant, Scientific Research Study Investigator, Research Grant or Support, Speaker’s Bureau)Janssen (Consultant, Research Grant or Support, Speaker’s Bureau)Merck (Research Grant or Support, Speaker’s Bureau)ViiV Healthcare (Consultant, Speaker’s Bureau)

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638. Safety, Efficacy, and Durability of Long-Acting CAB and RPV as Maintenance Therapy for HIV-1 Infection: LATTE-2 Week 256 Results

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.832 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S379-S380

Author(s):

Graham Smith ◽

Keith Henry ◽

Daniel Podzamczer ◽

Mar Masiá ◽

Christopher Bettacchi ◽

...

Keyword(s):

Panel Member ◽

Virologic Response ◽

Research Support ◽

Review Panel ◽

Material Support ◽

Grade 3 ◽

Long Acting ◽

Hiv 1 ◽

Research Grant

Abstract Background Long-acting (LA) injectable suspensions of cabotegravir (CAB) & rilpivirine (RPV) are in phase III development. LATTE-2 W160 results demonstrated high rates of virologic response & overall tolerability. This W256 analysis evaluated long-term efficacy, safety, & tolerability of every 8-week (Q8W) & 4-week (Q4W) intramuscular (IM) dosing. Methods LATTE-2 is a phase IIb, multicenter, parallel arm, open-label study in antiretroviral therapy–naive adults with HIV. After a 20-week Induction Period on oral CAB+abacavir/lamivudine, participants (pts) with plasma HIV-1 RNA< 50c/mL were randomized 2:2:1 to IM CAB LA+RPV LA Q8W, Q4W, or continue oral (PO) regimen in the Maintenance Period (MP). After W96, pts on IM regimens continued their current MP regimen. Pts randomized to PO in MP chose a Q8W or Q4W IM regimen in the Extension Period (EP). W256 analysis of MP & EP included virologic success with HIV-1 RNA< 50 c/mL (Food & Drug Administration Snapshot analysis), protocol-defined virologic failure (PDVF), & safety (intention-to-treat–Maintenance Exposed population). Results At W256, 88% (101/115; Q8W) & 74% (85/115; Q4W) of randomized IM pts had HIV-1 RNA< 50 c/mL, as did 93% (41/44) of PO to IM pts. No pt developed PDVF after W48. In the randomized IM arm (MP & EP), excluding injection-site reactions (ISRs), nasopharyngitis (45%), diarrhea (28%), & headache (24%) were the most common adverse events (AEs), with 34% (39/115; Q8W) & 33% (38/115; Q4W) of pts reporting AEs ≥grade 3, of which 12% (14/115; Q8W) & 11% (13/115; Q4W) were drug related. 3% (3/115; Q8W) & 17% (20/115; Q4W) of pts had AEs leading to withdrawal. 22% (25/115; Q8W) & 23% (27/115; Q4W) reported serious AEs (3 were drug related). In the PO to IM arm (EP only), most common AEs excluding ISRs were nasopharyngitis (25%), influenza (23%), & back pain (18%). 23% (10/44) reported AEs ≥grade 3 & 5% (2/44) had AEs leading to withdrawal. Majority of ISRs were mild/moderate pain & discomfort. < 1% of ISRs were severe, with 5 pts discontinuing due to ISRs. Table 1 Table 2 Conclusion CAB+RPV LA injectable therapy, administered Q8W or Q4W, demonstrated high rates of virologic response & tolerability through 5 years. W256 results add to previous results & demonstrate long-term durability of CAB+RPV LA for people living with HIV. Disclosures Keith Henry, MD, Gilead (Research Grant or Support, Paid to institution)GSK/ViiV (Research Grant or Support, Paid to institution)Janssen (Research Grant or Support, Paid to institution)Merck (Research Grant or Support, Paid to institution) Daniel Podzamczer, MD, PhD, Gilead (Grant/Research Support, Advisor or Review Panel member)Janssen Pharmaceutica (Grant/Research Support, Advisor or Review Panel member)Merck Sharp & Dohme (Grant/Research Support, Advisor or Review Panel member)ViiV Healthcare (Grant/Research Support, Advisor or Review Panel member) Mar Masiá, MD, PhD, Janssen Pharmaceutica (Consultant, Other Financial or Material Support, Travel/accommodations/meeting expenses)Merck Sharp & Dohme (Consultant, Other Financial or Material Support, Travel/accommodations/meeting expenses)ViiV Healthcare (Consultant, Other Financial or Material Support, Travel/accommodations/meeting expenses) Hans Jaeger, MD, Abbvie (Consultant, Speaker’s Bureau)Gilead Sciences (Consultant, Speaker’s Bureau)Janssen (Consultant, Speaker’s Bureau)MSD Sharp & Dohme (Consultant, Speaker’s Bureau)ViiV Healthcare (Consultant, Research Grant or Support, Speaker’s Bureau) Marie-Aude Khuong-Josses, MD, Viiv HC (Advisor or Review Panel member) Kenneth Sutton, MA, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Cynthia C. McCoig, MD, ViiV Healthcare (Employee) Kati Vandermeulen, MSC, Janssen Pharmaceutica (Employee, Shareholder) Rodica Van Solingen-Ristea, MD, Janssen R&D (Employee) William Spreen, PharmD, ViiV Healthcare (Employee, Shareholder) David Margolis, MD, MPH, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee)

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72. Remdesivir vs Standard Care in Patients with Moderate covid-19

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.382 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S166-S167

Author(s):

Francisco M Marty ◽

Prashant Malhotra ◽

Robert L Gottlieb ◽

Karen T Tashima ◽

Massimo Galli ◽

...

Keyword(s):

Research Study ◽

Clinical Status ◽

Scientific Research ◽

Panel Member ◽

Ordinal Scale ◽

Research Support ◽

Review Panel ◽

Material Support ◽

Study Investigator ◽

Research Grant

Abstract Background Remdesivir (RDV) shortens time to recovery time in patients with severe COVID-19. Its effect in patients with moderate COVID-19 remains unclear. Methods We conducted an open-label, phase 3 trial (NCT04252664) involving hospitalized patients with confirmed SARS-CoV-2 infection, evidence of pulmonary infiltrates, and oxygen saturation >94% on room air. Patients were randomly assigned 1:1:1 to receive up to 5d or 10d of RDV with standard of care (SoC), or SoC alone; patients could be discharged prior to completing per-protocol assigned treatment duration. RDV was dosed intravenously at 200 mg on d1, 100 mg daily thereafter. Patients were evaluated daily while hospitalized, and via telephone if discharged. The primary endpoint was clinical status on d11 assessed on a 7-point ordinal scale. Results regarding the primary endpoint are expected to be published before IDWeek 2020; we plan to present d28 results at the meeting. Results In total, 584 patients underwent randomization and started their assigned treatment (191, 5d RDV; 193, 10d RDV; 200, SoC). By d11, ³ 2 point improvement on the ordinal scale occurred in 70% of patients in the 5d arm, 65% in the 10d arm, and 61% in the SoC arm. Patients in the 5d RDV arm were significantly more likely to have an improvement in clinical status than those receiving SoC (odds ratio [OR], 1.65; 95% confidence interval [CI], 1.09–2.48; P=0.017); OR of improvement for the 10d RDV arm compared to SoC was 1.31 (95% CI, 0.88–1.95]; p=0.183). This improvement in the 5-day arm over the SOC arm was noted from d6 through d11. We observed a peak of discharges corresponding with the assigned treatment duration of RDV, with increased discharges at d6 in the 5-day arm and at d11 in the 10-day arm. A worsening of clinical status of ≥ 1 point in the ordinal scale was observed more commonly in the SoC am (n=19, 10%) versus the 5d RDV (n=7, 4%) and 10d RDV (n=9, 5%). Conclusion RDV for up to 5 days was superior to SoC in improving the clinical status of patients with moderate COVID-19 by d11. We will report d28 outcomes at the meeting. Disclosures Francisco M. Marty, MD, Allovir (Consultant)Amplyx (Consultant)Ansun (Scientific Research Study Investigator)Avir (Consultant)Cidara (Scientific Research Study Investigator)F2G (Consultant, Scientific Research Study Investigator)Kyorin (Consultant)Merck (Consultant, Grant/Research Support, Scientific Research Study Investigator)New England Journal of Medicine (Other Financial or Material Support, Honorarium for Video)Regeneron (Consultant, Scientific Research Study Investigator)ReViral (Consultant)Scynexis (Scientific Research Study Investigator)Symbio (Consultant)Takeda (Scientific Research Study Investigator)United Medical (Consultant)WHISCON (Scientific Research Study Investigator) Prashant Malhotra, MD, Gilead Sciences Inc. (Scientific Research Study Investigator) Robert L. Gottlieb, MD, Gilead Sciences Inc. (Scientific Research Study Investigator) Karen T. Tashima, MD, Bristol-Myers Squibb (Research Grant or Support)Gilead Sciences Inc. (Grant/Research Support, Scientific Research Study Investigator)GlaxoSmithKline (Research Grant or Support)Merck (Research Grant or Support)Tibotec (Research Grant or Support)Viiv Healthcare (Research Grant or Support) Massimo Galli, MD, Gilead Sciences Inc. (Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member, Other Financial or Material Support, Personal fees) Louis Yi Ann Chai, MD, Gilead Sciences Inc. (Scientific Research Study Investigator) Devi SenGupta, MD, Gilead Sciences Inc. (Employee, Shareholder) Robert H. Hyland, MD, Gilead Sciences Inc. (Employee, Shareholder) Hongyuan Wang, PhD, Gilead Sciences Inc. (Employee, Shareholder) Lijie Zhong, PhD, Gilead Sciences Inc. (Employee, Shareholder) Huyen Cao, MD, Gilead Sciences Inc. (Employee, Shareholder) Anand Chokkalingam, PhD, Gilead Sciences (Employee) Anu Osinusi, MD, Gilead Sciences (Employee) Diana M. Brainard, MD, Gilead Sciences (Employee) Michael Brown, MD, Gilead Sciences Inc. (Scientific Research Study Investigator) Ane Josune Goikoetxea, MD, Gilead Sciences Inc. (Scientific Research Study Investigator) Mamta Jain, MD, Gilead Sciences Inc. (Scientific Research Study Investigator, Research Grant or Support)GlaxoSmithKline (Advisor or Review Panel member)Janssen (Research Grant or Support)Merck (Research Grant or Support) David Shu Cheong Hui, MD, Gilead Sciences Inc. (Scientific Research Study Investigator) Enos Bernasconi, MD, Gilead Sciences Inc. (Scientific Research Study Investigator) Christoph Spinner, MD, AbbVie (Advisor or Review Panel member, Other Financial or Material Support, Travel)Bristol-Myers Squibb (Grant/Research Support, Advisor or Review Panel member, Other Financial or Material Support, Travel)Gilead Sciences Inc. (Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member, Other Financial or Material Support, Travel)Janssen (Grant/Research Support, Advisor or Review Panel member, Other Financial or Material Support, Travel)MSD (Grant/Research Support, Advisor or Review Panel member, Other Financial or Material Support, Travel)Viiv Healthcare (Grant/Research Support, Advisor or Review Panel member, Other Financial or Material Support, Travel)

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1248. Efficacy and Safety of Oral Ibrexafungerp in 41 Patients with Refractory Fungal Diseases, Interim Analysis of a Phase 3 Open-label Study (FURI)

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1432 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S642-S642

Author(s):

Barbara D Alexander ◽

Oliver Cornely ◽

Peter Pappas ◽

Rachel Miller ◽

Jose A Vazquez ◽

...

Keyword(s):

Research Study ◽

Scientific Research ◽

Panel Member ◽

Research Support ◽

Open Label ◽

Review Panel ◽

Phase 3 ◽

Material Support ◽

Study Investigator ◽

Research Grant

Abstract Background Candida infections resistant to currently available antifungals are an emerging global threat. Ibrexafungerp is an investigational broad-spectrum glucan synthase inhibitor antifungal with activity against Candida and Aspergillus species, including azole- and echinocandin-resistant strains. A Phase 3 open-label, single-arm study of oral ibrexafungerp (FURI) (Clinicaltrials.gov NCT03059992) is ongoing for the treatment of patients (≥18 years) with fungal diseases who are intolerant of or refractory to standard antifungal therapies. Methods An independent Data Review Committee (DRC) provided an assessment of treatment response for 41 patients. Patients were enrolled in 22 centers from 6 countries. Patients were eligible for enrollment if they had proven or probable, invasive or severe mucocutaneous candidiasis and documented evidence of failure of, intolerance to, or toxicity related to a currently approved standard-of-care antifungal treatment or could not receive approved oral antifungal options (e.g., susceptibility of the organism) and a continued IV antifungal therapy was undesirable or unfeasible. Results The 41 patients assessed had the following infection types: intra-abdominal abscesses, oropharyngeal candidiasis, esophageal candidiasis, candidemia, and others. The DRC adjudicated 23 patients (56%) as achieving complete or partial response, 11 patients (27%) maintaining stable disease, 6 patients (15%) with progression of disease and one case was considered as indeterminate. The efficacy of oral ibrexafungerp by pathogen is shown in Table 1. Ibrexafungerp was well-tolerated with the most common treatment-related adverse events being of gastrointestinal origin. No deaths due to progression of fungal disease were reported. Table 1: Ibrexafungerp Outcomes by Pathogen Conclusion Preliminary analysis of these 41 cases indicate that oral ibrexafungerp provides a favorable therapeutic response in the majority of patients with difficult to treat Candida spp. infections, including those caused by non-albicans Candida species. Disclosures Barbara D. Alexander, MD, MHS, SCYNEXIS, Inc. (Employee, Scientific Research Study Investigator, Research Grant or Support) Oliver Cornely, Prof., Actelion (Grant/Research Support)Actelion (Other Financial or Material Support, Personal fees)Al Jazeera Pharmaceuticals (Consultant)Allecra Therapeutics (Other Financial or Material Support, Personal fees)Amplyx (Other Financial or Material Support, Personal fees)Amplyx (Grant/Research Support)Astellas (Grant/Research Support)Astellas (Other Financial or Material Support, Personal fees)Basilea (Other Financial or Material Support, Personal fees)Basilea (Grant/Research Support)Biosys UK Limited (Other Financial or Material Support, Personal fees)Cidara (Other Financial or Material Support, Personal fees)Cidara (Grant/Research Support)Da Volterra (Grant/Research Support)Da Volterra (Other Financial or Material Support, Personal fees)Entasis (Other Financial or Material Support, Personal fees)F2G (Other Financial or Material Support)F2G (Grant/Research Support)Gilead (Grant/Research Support)Gilead (Other Financial or Material Support, Personal fees)Grupo Biotoscana (Other Financial or Material Support, Personal fees)Janssen Pharmaceuticals (Grant/Research Support)Matinas (Other Financial or Material Support, Personal fees)Medicines Company (Grant/Research Support)MedPace (Grant/Research Support)MedPace (Other Financial or Material Support, Personal fees)Melinta Therapeutics (Grant/Research Support)Menarini Ricerche (Other Financial or Material Support, Personal fees)Merck/MSD (Other Financial or Material Support, Personal fees)Merck/MSD (Grant/Research Support)Mylan Pharmaceuticals (Consultant)Nabriva Therapeutics (Other Financial or Material Support, Personal fees)Octapharma (Other Financial or Material Support, Personal fees)Paratek Pharmaceuticals (Other Financial or Material Support, Personal fees)Pfizer (Other Financial or Material Support, Personal fees)Pfizer (Grant/Research Support)PSI (Other Financial or Material Support, Personal fees)Rempex (Other Financial or Material Support, Personal fees)Roche Diagnostics (Other Financial or Material Support, Personal fees)Scynexis (Other Financial or Material Support, Personal fees)Scynexis (Grant/Research Support)Seres Therapeutics (Other Financial or Material Support, Personal fees)Tetraphase (Other Financial or Material Support, Personal fees) Peter Pappas, MD, SCYNEXIS, Inc. (Consultant, Advisor or Review Panel member, Research Grant or Support) Rachel Miller, MD, SCYNEXIS, Inc. (Scientific Research Study Investigator) Luis Ostrosky-Zeichner, MD, Amplyx (Scientific Research Study Investigator)Astellas (Consultant, Scientific Research Study Investigator, Other Financial or Material Support, Non-branded educational speaking)Biotoscana (Consultant, Other Financial or Material Support, Non-branded educational speaking)Cidara (Consultant, Scientific Research Study Investigator)F2G (Consultant)Gilead (Consultant)Mayne (Consultant)Octapharma (Consultant)Pfizer (Other Financial or Material Support, Non-branded educational speaking)Scynexis (Consultant, Grant/Research Support, Scientific Research Study Investigator)Stendhal (Consultant)Viracor (Consultant) Andrej Spec, MD, SCYNEXIS, Inc. (Scientific Research Study Investigator, Advisor or Review Panel member) Riina Rautemaa-Richardson, DDS, PhD, FRCPath, SCYNEXIS, Inc. (Scientific Research Study Investigator) Robert Krause, MD, SCYNEXIS, Inc. (Scientific Research Study Investigator) Caryn Morse, MD, SCYNEXIS, Inc. (Scientific Research Study Investigator) John W. Sanders, III, MD, SCYNEXIS, Inc. (Scientific Research Study Investigator) David Andes, MD, SCYNEXIS, Inc. (Scientific Research Study Investigator, Advisor or Review Panel member) George Lyon, MD, SCYNEXIS, Inc. (Scientific Research Study Investigator) Francisco M. Marty, MD, Allovir (Consultant)Amplyx (Consultant)Ansun (Scientific Research Study Investigator)Avir (Consultant)Cidara (Scientific Research Study Investigator)F2G (Consultant, Scientific Research Study Investigator)Kyorin (Consultant)Merck (Consultant, Grant/Research Support, Scientific Research Study Investigator)New England Journal of Medicine (Other Financial or Material Support, Honorarium for Video)Regeneron (Consultant, Scientific Research Study Investigator)ReViral (Consultant)Scynexis (Scientific Research Study Investigator)Symbio (Consultant)Takeda (Scientific Research Study Investigator)United Medical (Consultant)WHISCON (Scientific Research Study Investigator) Marisa H. Miceli, MD, FIDSA, SCYNEXIS, Inc. (Advisor or Review Panel member) Thomas F. Patterson, MD, SCYNEXIS, Inc. (Advisor or Review Panel member) Martin Hoenigl, MD, SCYNEXIS, Inc. (Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member) Nkechi Azie, MD, SCYNEXIS, Inc. (Employee, Shareholder) David A. Angulo, MD, SCYNEXIS, Inc. (Employee, Shareholder)

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