LB1. Remdesivir for the Treatment of High-Risk Non-Hospitalized Individuals With COVID-19: A Randomized, Double-Blind, Placebo-Controlled Trial

Abstract Background Remdesivir (RDV) is a potent nucleotide prodrug inhibitor of the SARS-CoV-2 RNA-dependent RNA polymerase that has demonstrated efficacy in the treatment of patients hospitalized with moderate to severe COVID-19. This Phase 3 (GS-US-540–9012) double-blind, placebo-controlled study compared the efficacy and safety of 3 days of RDV to standard of care in non-hospitalized, high-risk participants with confirmed COVID-19. Table 1. COVID-19 related hospitalization or death, COVID-19 related medically attended visits or death, and Treatment Emergent Adverse Events Methods Participants were randomly assigned 1:1 to receive intravenous (IV) RDV (200 mg on day 1, 100 mg on days 2 to 3) or placebo. The primary efficacy endpoint was composite COVID-19 hospitalization or all-cause death by day 28 and compared using Cox proportional hazards model with baseline stratification factors as covariates. The primary safety endpoint was proportion of participants with treatment-emergent adverse events. Study enrollment was terminated early for administrative reasons in light of the evolving pandemic. Results 562 patients underwent randomization and started their assigned treatment (279, RDV; 283, placebo). Baseline demographics and characteristics were balanced across arms. Overall, 52% were male, 44% were Hispanic/Latino ethnicity and 30% were ≥ 60 years old. The most common comorbidities were diabetes mellitus (62%), obesity (56%; median BMI, 30.7), and hypertension (48%). Median baseline SARS-CoV-2 RNA nasopharyngeal viral load was 6.2 log10 copies/mL. Treatment with RDV significantly reduced COVID-19 hospitalization or all-cause death by day 28 (HR, 0.13; 95% CI, 0.03 – 0.59; p = 0.008; Table 1) compared to placebo. Participants receiving RDV also had significantly lower risk for COVID-19-related medically attended visits or all-cause death by day 28 compared to placebo (HR, 0.19; 95% CI, 0.07 – 0.56; p = 0.002; Table 1). No deaths occurred in either arm by day 28. There was no difference between arms in time-weighted average change in nasopharyngeal viral loads from baseline up to day 7. The proportion of patients with AEs was similar between arms (Table 1); the most common AEs in the RDV arm were nausea (11%), headache (6%), and diarrhea (4%). Conclusion A 3-day course of IV RDV was safe, well tolerated and highly effective at preventing COVID-19 related hospitalization or death in high-risk non-hospitalized COVID-19 patients. Disclosures Joshua A. Hill, MD, Allogene (Individual(s) Involved: Self): Consultant; Allovir (Individual(s) Involved: Self): Consultant, Grant/Research Support; Amplyx (Individual(s) Involved: Self): Consultant; Covance/CSL (Individual(s) Involved: Self): Consultant; CRISPR (Individual(s) Involved: Self): Consultant; Gilead (Individual(s) Involved: Self): Consultant, Grant/Research Support; Karius: Grant/Research Support, Scientific Research Study Investigator; Medscape (Individual(s) Involved: Self): Consultant; Octapharma (Individual(s) Involved: Self): Consultant; OptumHealth (Individual(s) Involved: Self): Consultant; Takeda (Individual(s) Involved: Self): Consultant, Grant/Research Support, Scientific Research Study Investigator Roger Paredes, MD, PhD, Gilead Sciences, Inc (Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member) Carlos Vaca, MD, Gilead Sciences, Inc (Scientific Research Study Investigator) Jorge Mera, MD, Gilead Sciences, Inc (Consultant, Study Investigator (payment to employer not self)) Gilberto Perez, MD, Gilead Sciences, Inc (Scientific Research Study Investigator) Godson Oguchi, MD, Gilead Sciences, Inc (Scientific Research Study Investigator) Pablo Ryan, MD PhD, Gilead Sciences, Inc (Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member) Jan Gerstoft, MD, Gilead Sciences, Inc (Other Financial or Material Support, Study Investigator (payment to employer)) Michael Brown, FRCP PhD, Gilead Sciences, Inc (Scientific Research Study Investigator, Investigator for numerous remdesivir trials (employer received compensation)) Morgan Katz, MD, MHS, Roche (Individual(s) Involved: Self): Advisor or Review Panel member; Skinclique (Individual(s) Involved: Self): Consultant Gregory Camus, PhD, Gilead Sciences (Employee, Shareholder) Danielle P. Porter, PhD, Gilead Sciences (Employee, Shareholder) Robert H. Hyland, DPhil, Gilead Sciences, Inc (Shareholder, Other Financial or Material Support, Employee during the conduct of this trial) Shuguang Chen, PhD, Gilead Sciences, Inc (Employee, Shareholder) Kavita Juneja, MD, Gilead Sciences, Inc (Employee) Anu Osinusi, MD, Gilead Sciences, Inc (Employee, Shareholder) Frank Duff, MD, Gilead Sciences, Inc (Employee, Shareholder) Robert L. Gottlieb, MD, Eli Lilly (Scientific Research Study Investigator, Advisor or Review Panel member)Gilead Sciences (Scientific Research Study Investigator, Advisor or Review Panel member, Other Financial or Material Support, Gift in kind to Baylor Scott and White Research Institute for NCT03383419)GSK (Advisor or Review Panel member)Johnson and Johnson (Scientific Research Study Investigator)Kinevant (Scientific Research Study Investigator)Roche/Genentech (Scientific Research Study Investigator)

Download Full-text

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)

Download Full-text

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)

Download Full-text

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)

Download Full-text

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)

Download Full-text

502. Early COVID-19 Treatment with SARS-CoV-2 Neutralizing Antibody Sotrovimab

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.701 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S353-S354

Author(s):

Anil K Gupta ◽

Yaneicy Gonzalez Rojas ◽

Erick Juarez ◽

Manuel Crespo Casal ◽

Jaynier Moya ◽

...

Keyword(s):

Clinical Trial ◽

Research Study ◽

Scientific Research ◽

Panel Member ◽

Illness Management ◽

Research Support ◽

Review Panel ◽

Material Support ◽

Study Investigator ◽

Trial Investigator

Abstract Background COVID-19 disproportionately results in hospitalization and death in older patients and those with underlying comorbidities. Sotrovimab is a pan-sarbecovirus monoclonal antibody that binds a highly conserved epitope of the SARS-CoV-2 receptor binding domain and has an Fc modification that increases half-life. Sotrovimab retains activity against UK, S. Africa, Brazil, India, New York and California variants in vitro. Objectives To evaluate the efficacy and safety of treatment with sotrovimab in high-risk, non-hospitalized patients with mild/moderate COVID-19, as part of the COMET-ICE clinical trial. Methods Multicenter, double-blind, phase 3 trial in non-hospitalized patients with symptomatic COVID-19 and ≥1 risk factor for disease progression were randomized 1:1 to an IV infusion of sotrovimab 500 mg or placebo. The primary efficacy endpoint was the proportion of patients with COVID-19 progression, defined as hospitalization > 24 hours or death, due to any cause, ≤29 days of randomization. Results The study met the pre-defined primary efficacy endpoint in a preplanned interim analysis: the risk of COVID-19 progression was significantly reduced by 85% (97.24% CI, 44% to 96%; P = 0.002) in 583 patients. In the final intention-to-treat analysis (N = 1057), the adjusted relative risk reduction was 79% (95% CI, 50% to 91%; p< 0.001) through Day 29 in recipients of sotrovimab (n=528) vs. placebo (n=529). Treatment with sotrovimab (ITT) resulted in a numerical reduction in the need for ER visits for illness management, hospitalization for acute illness management (any duration) or death (any cause) compared to placebo. No participants on sotrovimab required ICU admission, compared to 9 participants on placebo, of whom 4 participants required mechanical ventilation. No participants who received sotrovimab died, compared to 4 participants on placebo. The incidence of adverse events was similar between treatment arms and SAEs were numerically more common in the placebo arm. Conclusion Treatment with sotrovimab 500 mg IV resulted in a clinically and statistically significant reduction in progression of COVID-19 to hospitalization or death in patients with mild/moderate disease and was well-tolerated. Study funding GSK & VIR; NCT04545060 Disclosures Jaynier Moya, MD, VIR Biotechnology (Other Financial or Material Support, Jaynier Moya received non-financial support for serving as a clinical trial investigator for Vir Biotechnology) Diego Rodrigues Falci, MD, MSc, PhD, Gilead Sciences (Grant/Research Support, Scientific Research Study Investigator, Speaker's Bureau)GSK (Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member)MSD (Speaker's Bureau)Pfizer (Speaker's Bureau)United Medical (Speaker's Bureau, Other Financial or Material Support) Joel Solis, MD, VIR Biotechnology (Other Financial or Material Support, Joel Solis received non-financial support for serving as a clinical trial investigator for Vir Biotechnology) Hanzhe Zheng, PhD, VIR Biotechnology (Employee) Nicola Scott, MSc, GlaxoSmithKline (Employee, Shareholder) Andrea L. Cathcart, PhD, Gilead (Shareholder)VIR (Employee, Shareholder) Christy Hebner, PhD, Vir Biotechnology (Employee, Shareholder) Jennifer Sager, PhD, GSK (Other Financial or Material Support)Vir Biotechnology (Employee, Shareholder) Erik Mogalian, PharmD, PhD, Vir Biotechnology (Employee, Shareholder) Daren Austin, PhD, GlaxoSmithKline (Employee, Shareholder) Amanda Peppercorn, MD, GlaxoSmithKline (Employee) Elizabeth L. Alexander, MD, MSc, GlaxoSmithKline (Grant/Research Support, Other Financial or Material Support)VIR Biotechnology (Employee, Shareholder, GSK pharmaceuticals) Wendy W. Yeh, MD, Vir Biotechnology (Employee) Almena Free, MD, Amgen (Scientific Research Study Investigator)Astra Zeneca (Scientific Research Study Investigator)Cardurian (Scientific Research Study Investigator)Coherus (Scientific Research Study Investigator)Freenome (Scientific Research Study Investigator)GlaxoSmithKline/Vir (Scientific Research Study Investigator)Ionis (Scientific Research Study Investigator)Kowa (Scientific Research Study Investigator)New Amsterdam (Scientific Research Study Investigator)Regenacy (Scientific Research Study Investigator)Romark (Scientific Research Study Investigator)Scynexis (Scientific Research Study Investigator) 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) Melissa Aldinger, PharmD, VIR Biotechnology (Employee) Adrienne Shapiro, MD, PhD, Vir Biotechnology (Scientific Research Study Investigator)

Download Full-text

21. Efficacy and Safety of Maribavir as a Rescue Treatment for Investigator Assigned Therapy in Transplant Recipients With Refractory or Resistant Cytomegalovirus Infections in the SOLSTICE Study: Phase 3 Trial Results

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.021 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S14-S15

Author(s):

Marcus Pereira ◽

Carlos Cervera ◽

Camille Kotton ◽

Joseph Sasadeusz ◽

...

Keyword(s):

Research Study ◽

Symptom Control ◽

Scientific Research ◽

Panel Member ◽

Cmv Infection ◽

Research Support ◽

Review Panel ◽

Material Support ◽

Study Investigator

Abstract Background Refractory or resistant (R/R) cytomegalovirus (CMV) infection after hematopoietic cell transplant (HCT) and solid organ transplant (SOT) cause serious, potentially fatal complications; therapeutic options are limited. In a Phase 3 study (NCT02931539), maribavir (MBV) was superior to investigator-assigned therapy (IAT; val/ganciclovir, foscarnet, cidofovir) for CMV clearance (Wk 8) and clearance plus symptom control (Wk 8 through Wk 16) in HCT/SOT recipients with R/R CMV infections. Here we present further study results on efficacy and safety of MBV in the rescue arm. Methods Patients (pts) were stratified and randomized 2:1 to MBV (400 mg/bid) or IAT for 8-wk treatment then 12-wk follow-up. After minimum 3 wks’ treatment, pts in the IAT group meeting criteria (worsening/lack of improvement of CMV infection or failure to achieve viremia clearance plus IAT intolerance) could enter a MBV rescue arm (8-wk treatment, 12-wk follow-up). In the rescue arm, efficacy was evaluated by confirmed CMV viremia clearance (plasma CMV DNA < 137 IU/mL in 2 consecutive tests ≥ 5 days apart) at end of Wk 8 and confirmed clearance with symptom control at Wk 8 through Wk 16. Safety was assessed. Results A total of 352 pts were randomized (MBV: 235, IAT: 117, randomized set). Confirmed CMV viremia clearance at Wk 8 was achieved in 131 (55.7%) and 28 (23.9%) pts, respectively, in the randomized set. Having met criteria, 22 (18.8%) pts entered the MBV rescue arm; at entry, 6 (27.3%) pts had developed neutropenia and 9 (40.9%) had increased serum creatinine (Table 1). At Wk 8 of rescue therapy, 11 (50.0%) pts achieved confirmed CMV viremia clearance; 6 (27.3%) pts had CMV clearance with symptom control at Wk 8 maintained through Wk 16 (Table 2). All 22 pts reported treatment-emergent adverse events (TEAEs; Table 3); most common TEAEs of special interest were nausea, vomiting, and diarrhea (54.5%), and taste disturbance (50.0%). Neutropenia and acute kidney injury TEAEs were reported by 0 and 3 pts in the rescue arm, respectively. Table 1. Summary of patients from IAT-randomized group meeting criteria for entry into MBV rescue arm* Table 2. Patients achieving confirmed CMV viremia clearance at end of Wk 8 (end of treatment) or achieving confirmed CMV viremia clearance and symptom control at end of Wk 8 maintained through Wk 16 Table 3. Treatment-emergent adverse events during the on-rescue observation period Conclusion Rescue arm data show MBV was efficacious for R/R CMV infection in HCT/SOT recipients inadequately responding to IAT with/without intolerance and had a similar safety profile to that reported for pts in the randomized MBV group. Disclosures Marcus Pereira, MD, Hologic (Scientific Research Study Investigator)Merck (Scientific Research Study Investigator)Takeda (Scientific Research Study Investigator, Advisor or Review Panel member) Carlos Cervera, MD, PhD, Avir Pharma (Consultant, Advisor or Review Panel member)Lilly (Consultant, Advisor or Review Panel member)Merck (Consultant, Advisor or Review Panel member, Research Grant or Support)Sunovion (Consultant, Advisor or Review Panel member)Takeda (Consultant, Advisor or Review Panel member)Veritas Pharma (Consultant, Advisor or Review Panel member) Camille Kotton, MD, Shire/Takeda (Advisor or Review Panel member) Camille Kotton, MD, UpToDate (Individual(s) Involved: Self): I write chapters on zoonoses for UpToDate., Independent Contractor Joseph Sasadeusz, MBBS, PhD, Abbvie (Grant/Research Support, Other Financial or Material Support, Consulting fee: speaker)Gilead (Other Financial or Material Support, Speaker)Merck (Grant/Research Support, Consulting fee: speaker)Takeda (Grant/Research Support) Jingyang Wu, MS, Shire Human Genetic Therapies, Inc., a Takeda company (Employee, Other Financial or Material Support, Holds stock/stock options) Martha Fournier, MD, Shire Human Genetic Therapies, Inc., a Takeda company (Employee, Other Financial or Material Support, Holds stock/stock options)Shire ViroPharma, a Takeda company (Other Financial or Material Support, This study was funded by Shire ViroPharma, a Takeda company)

Download Full-text

38. Remdesivir Treatment in Patients Hospitalized with COVID-19: A Comparative Analysis of In-Hospital All-Cause Mortality

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.038 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S27-S28

Author(s):

Essy Mozaffari ◽

Aastha Chandak ◽

Zhiji Zhang ◽

Shuting Liang ◽

Mark Thrun ◽

...

Keyword(s):

Research Study ◽

Scientific Research ◽

Panel Member ◽

High Flow ◽

Low Flow ◽

Research Support ◽

Review Panel ◽

Material Support ◽

Risk Of Death ◽

Study Investigator

Abstract Background Remdesivir (RDV) reduced time to recovery and mortality in some subgroups of hospitalized patients in the NIAID ACTT-1 RCT compared to placebo. Comparative effectiveness data in clinical practice are limited. Methods Using the Premier Healthcare Database, we compared survival for adult non-mechanically ventilated hospitalized COVID-19 patients between Aug-Nov 2020 and treated with RDV within 2 days of hospitalization vs. those who did not receive RDV. Preferential within-hospital propensity score matching with replacement was used. Patients were matched on baseline O2 and 2-month admission period and were excluded if discharged within 3 days of RDV initiation (to exclude anticipated discharges/transfers within 72 hrs consistent with ACTT-1 study). Time to 14- and 28-day mortality was examined separately for patients on high-flow/non-invasive ventilation (NIV), low-flow, and no supplemental O2 using Cox Proportional Hazards models. Results RDV patients (n=27,559) were matched to unique non-RDV patients (n=15,617) (Fig 1). The two groups were balanced; median age 66 yrs and 73% white (RDV); 68 yrs and 74% white (non-RDV), and 55% male. At baseline, 21% required high-flow O2, 50% low-flow O2, and 29% no O2, overall. Mortality in RDV patients was 9.6% and 13.8% on days 14 and 28, respectively. For non-RDV patients, mortality was 14.0% and 17.3% on days 14 and 28, respectively. Kaplan-Meier curves for time to mortality are shown in Fig 2. After adjusting for baseline and clinical covariates, RDV patients on no O2 and low-flow O2 had a significantly lower risk of death within 14 days (no O2, HR: 0.69, 95% CI: 0.57—0.83; low-flow, HR: 0.67, 95% CI: 0.59—0.77) and 28 days (no O2, HR: 0.80, 95% CI: 0.68—0.94; low-flow, HR: 0.76, 95% CI: 0.68—0.86). Additionally, RDV patients on high-flow O2/NIV had a significantly lower risk of death within 14 days (HR: 0.81, 95% CI: 0.70—0.93); but not at 28 days (Fig 3). Fig 1. Study Population Fig 2. Kaplan-Meier curves among matched patients hospitalized for COVID-19, August-November 2020 Fig 3. Cox proportional hazard model* for time to mortality among matched patients hospitalized for COVID-19, August-November 2020 Conclusion In this large study of patients in clinical care hospitalized with COVID-19, we observed a significant reduction of mortality in RDV vs. non-RDV treated patients in those on no O2 or low-flow O2. Mortality reduction was also seen in patients on high-flow O2 at day 14, but not day 28. These data support the use of RDV early in the course of COVID-19 in hospitalized patients. Disclosures Essy Mozaffari, PharmD, MPH, MBA, Gilead Sciences (Employee, Shareholder) Aastha Chandak, PhD, Gilead Sciences (Other Financial or Material Support, Employee of Certara (contracted by Gilead to conduct this study)) Zhiji Zhang, MS, Gilead Sciences (Other Financial or Material Support, Employee of Certara (contracted by Gilead to conduct this study)) Shuting Liang, MPH, Gilead Sciences (Employee) Mark Thrun, MD, Gilead Sciences (Employee, Shareholder) Robert L. Gottlieb, MD, Eli Lilly (Scientific Research Study Investigator, Advisor or Review Panel member)Gilead Sciences (Scientific Research Study Investigator, Advisor or Review Panel member, Other Financial or Material Support, Gift in kind to Baylor Scott and White Research Institute for NCT03383419)GSK (Advisor or Review Panel member)Johnson and Johnson (Scientific Research Study Investigator)Kinevant (Scientific Research Study Investigator)Roche/Genentech (Scientific Research Study Investigator) Daniel R. Kuritzkes, MD, Abpro (Consultant)Atea (Consultant, Scientific Research Study Investigator)Decoy (Consultant)Gilead Sciences (Consultant, Grant/Research Support)GSK (Consultant)Janssen (Consultant)Merck (Consultant, Grant/Research Support)Novartis (Scientific Research Study Investigator)Rigel (Consultant)ViiV (Consultant, Grant/Research Support) Paul Sax, MD, Gilead Sciences (Consultant, Grant/Research Support)Janssen (Consultant)Merck (Consultant, Research Grant or Support)ViiV (Consultant, Research Grant or Support) David Wohl, MD, Gilead Sciences (Consultant, Grant/Research Support, Advisor or Review Panel member)Janssen (Consultant, Advisor or Review Panel member)Merck (Consultant, Grant/Research Support, Advisor or Review Panel member)ViiV (Consultant, Grant/Research Support, Advisor or Review Panel member) Roman Casciano, M.Eng, Gilead Sciences (Other Financial or Material Support, Employee of Certara (contracted by Gilead to conduct this study)) Paul Hodgkins, PhD, MSc, Gilead Sciences (Employee, Shareholder) Richard Haubrich, MD, Gilead Sciences (Employee, Shareholder)

Download Full-text

354. SARS-CoV-2 Viral Viability Culture and Sequencing from Immunocompromised Patients with Persistently Positive SARS-CoV-2 PCR Results

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.555 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S281-S281

Author(s):

Abby Sung ◽

Adam Bailey ◽

Meghan Wallace ◽

Henry B Stewart ◽

David McDonald ◽

...

Keyword(s):

Research Study ◽

Scientific Research ◽

Panel Member ◽

Research Support ◽

Review Panel ◽

Material Support ◽

Study Investigator ◽

Jewish Hospital ◽

Support Research ◽

Research Grant

Abstract Background Immunocompromised (IC) patients (pts) can have prolonged SARS-CoV-2 PCR positivity, even after resolution of COVID-19 symptoms. This study aimed to determine if viable virus could be detected in samples collected > 21 days after an initial positive (pos) SARS-CoV-2 PCR in IC pts. Methods We obtained 20 remnant SARS-CoV-2 PCR pos nasopharyngeal swabs from IC pts (bone marrow or solid organ transplant, high dose steroids, immunosuppressive medications) with a pos repeat PCR within the previous 30 days. The repeat specimens were cultured on Vero-hACE2-TMPRSS2 cells and incubated for 96 hours to assess viral viability. Viable RNA and infectious virus in the cultured cells were measured by qPCR and infectious plaque assays. RNA sequencing was performed on a HiSeq platform (Illumina). Samples also underwent SARS-CoV-2 antigen (Ag) testing (BD Veritor). Clinical data were extracted from the electronic health record by chart review. Results Pt characteristics are in Table 1. Viral cultures from the repeat specimen were negative (neg) for 18 pts and pos for 2 (Table 2). Pt 1 is a 60M treated with obinatuzumab 19 days prior to his first pos PCR test, with repeat specimen collected 21 days later (cycle threshold (Ct) not available). Pt 1 had a low viral titer (27 PFU/mL) & a D614G mutation on sequencing. Pt 2 is a 75M treated with rituximab 10 days prior to his first pos PCR test, with repeat specimen collected 23 days later (Ct 27.56/27.74). Pt 2 had a high viral titer (2e6 PFU/mL) and D614G, S98F, and S813I mutations. Demographics of Study Population (N=20) Characteristics of patients with a positive SARS-CoV-2 viral culture Conclusion 90% of specimens collected > 21 days after an initial pos SARS-CoV-2 PCR did not have viable virus detected on their repeat specimen. The 2 pts with pos viral cultures had active hematologic malignancies treated with an anti-CD20 mAb at the time of COVID-19 diagnosis. One pt had a high concentration of active, viable virus. No known variants of concern were noted in this cohort, collected in Q2 2020, though prolonged replication is a risk for variant development. Further data are needed about risk factors for persistent viable viral shedding & methods to prevent transmission of viable virus from IC hosts. Disclosures Victoria J. Fraser, MD, CDC Epicenters (Grant/Research Support)Cigna/Express Scripts (Other Financial or Material Support, Spouse is Chief Clinical Officer)Doris Duke Fund to Retain Clinical Scientists (Grant/Research Support, Research Grant or Support)Foundation for Barnes-Jewish Hospital (Grant/Research Support, Research Grant or Support)NIH (Grant/Research Support, Research Grant or Support) Victoria J. Fraser, MD, Centers for Disease Control and Prevention (Individual(s) Involved: Self): Grant/Research Support, Research Grant or Support; Cigna/Express Scripts (Individual(s) Involved: Spouse/Partner): Employee; Doris Duke Charitable Foundation (Individual(s) Involved: Self): Grant/Research Support, Research Grant or Support; National Institutes of Health (Individual(s) Involved: Self): Grant/Research Support, Research Grant or Support; The Foundation for Barnes-Jewish Hospital (Individual(s) Involved: Self): Grant/Research Support, Research Grant or Support Michael S. Diamond, MD, PhD, Carnival Corporation (Consultant)Emergent BioSolutions (Grant/Research Support)Fortress Biotech (Consultant)Immunome (Advisor or Review Panel member)Inbios (Consultant)Moderna (Grant/Research Support, Advisor or Review Panel member)Vir Biotechnology (Consultant, Grant/Research Support) Carey-Ann Burnham, PhD, BioFire (Grant/Research Support, Other Financial or Material Support)bioMerieux (Grant/Research Support)Cepheid (Consultant, Grant/Research Support)Luminex (Grant/Research Support)Roche (Other Financial or Material Support) Carey-Ann Burnham, PhD, BioFire (Individual(s) Involved: Self): Grant/Research Support; bioMerieux (Individual(s) Involved: Self): Grant/Research Support, Scientific Research Study Investigator, Speakers’ bureau; Cepheid (Individual(s) Involved: Self): Consultant, Grant/Research Support, Scientific Research Study Investigator; Luminex (Individual(s) Involved: Self): Scientific Research Study Investigator Hilary Babcock, MD, MPH, FIDSA, FSHEA, Nothing to disclose

Download Full-text

1184. A Phase 3, Multicenter, Randomized, Double-blind Study to Evaluate the Interchangeability of V114 and Prevnar 13™ with Respect to Safety, Tolerability, and Immunogenicity in Healthy Infants (PNEU-DIRECTION)

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.1376 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S684-S684

Author(s):

Adroniki Bili ◽

Scott Dobson ◽

Jeffrey Quinones ◽

Wanatpreeya Phongsamart ◽

Peninnah Oberdorfer ◽

...

Keyword(s):

Research Study ◽

Scientific Research ◽

Panel Member ◽

Research Support ◽

Review Panel ◽

Post Dose ◽

Double Blind ◽

Study Investigator ◽

Group 1 ◽

Research Grant

Abstract Background Pneumococcal diseases (PD) caused by Streptococcus pneumoniae are a major health concern globally. In children, currently licensed pneumococcal conjugate vaccines (PCVs) provide protection against PD from vaccine serotypes, but other non-vaccine serotypes have emerged and contribute to most residual disease. V114 is a 15-valent investigational PCV containing serotypes 22F and 33F in addition to the 13 serotypes shared by Prevnar 13TM (PCV13). This phase 3 study evaluated safety and immunogenicity of mixed PCV13/V114 regimens when changing from PCV13 to V114 at doses 2, 3, or 4. Methods In this double-blind trial, 900 infants were randomized in equal ratios to five treatment groups using a 3 + 1 immunization schedule (3-dose infant primary series followed by one toddler dose). Groups 2, 3, and 4 started with PCV13 and switched to V114 at doses 4, 3, and 2, respectively. Groups 1 and 5 received four doses of PCV13 and V114, respectively. Immunoglobulin G (IgG) responses to the 15 pneumococcal serotypes in V114 were measured at 30 days post-dose 3, prior to dose 4, and 30 days post-dose 4 (PD4). Primary immunogenicity analysis was based on 13 shared serotype responses at PD4. Safety was evaluated as the proportion of participants with adverse events (AEs). Results At 30 days PD4, IgG geometric mean concentrations (GMCs) for the 13 shared serotypes were generally comparable between V114/PCV13 mixed regimens (Groups 2-4) and participants that received the 4-dose PCV13 regimen (Group 1). Additionally, IgG GMCs for the 13 shared serotypes were generally comparable for participants that received the 4-dose V114 regimen (Group 5) and participants that received the 4-dose PCV13 regimen (Group 1). Infants given at least one dose of V114 mounted immune responses to two unique serotypes in V114 (22F and 33F). Frequency of injection-site and systemic AEs among study participants were generally comparable across all study groups. Conclusion V114 was well tolerated with a generally comparable safety profile to PCV13. For the 13 shared serotypes, both mixed-dose and 4-dose regimens of V114 induced generally comparable antibody responses to a PCV13 4-dose regimen. Study results support interchangeability of V114 with PCV13 in infants. Disclosures Adroniki Bili, MD, Merck & Co., Inc. (Employee, Shareholder) 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) Marissa B. Wilck, MD, Merck & Co., Inc. (Employee, Shareholder) Waldimir Vallejos, MD, Merck & Co., Inc. (Employee, Shareholder) Christine Nunn, MS, Merck & Co., Inc. (Employee, Shareholder) Richard McFetridge, B.S., Merck & Co., Inc (Employee) Rong Fu, PhD, MSD China (Employee, Shareholder) Robert Lupinacci, M.S, Merck & Co., Inc (Employee, Shareholder) Luwy Musey, MD, Merck & Co., Inc. (Employee) Kara Bickham, MD, Merck Sharp and Dohme (Employee, Shareholder)

Download Full-text

120. An open-label comparative trial of SUBA-itraconazole (SUBA) versus conventional itraconazole (c-itra) for treatment of proven and probable endemic mycoses (MSG-15): a pharmacokinetic (PK) and adverse Event (AE) analysis

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.120 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S72-S72

Author(s):

Peter G Pappas ◽

Andrej Spec ◽

Marisa Miceli ◽

Gerald McGwin ◽

Rachel McMullen ◽

...

Keyword(s):

Research Study ◽

Scientific Research ◽

Panel Member ◽

Serum Levels ◽

Research Support ◽

Open Label ◽

Review Panel ◽

Study Investigator ◽

Endemic Mycoses ◽

Research Grant

Abstract Background C-itra is the drug of choice for treatment of most non-CNS, non-life-threatening forms of endemic mycoses (EM), including histoplasmosis, blastomycosis, coccidioidomycosis, sporotrichosis and talaromycosis. SUBA represents a new formulation of itraconazole that utilizes nanotechnology to improve bioavailability when administered orally. SUBA is formulated as nanoparticles allowing for absorption in the small bowel while not relying on gastric acidity for optimal absorption. MSG-15 is an open-label, comparative clinical trial comparing SUBA to c-itra for the treatment of EM. Herein we report the final PK and AE profiles of these two compounds. Methods Subjects with proven and probable EM were eligible this open-label comparative study. The protocol allowed up to 14 d of prior therapy with any antifungal for this episode of EM. Subjects were randomized to receive either SUBA 130 mg po bid or c-itra 200 mg po bid for up to 6 months. Follow up occurred at 7, 14, 28, 42, 84 and 180 d post-enrollment. PK samples were obtained at 7, 14, and 42 d. Clinical assessment, including symptom assessment, AEs, overall drug tolerance, and quality of life were assessed at each visit. We used descriptive statistics for this analysis. Results 89 subjects with EM entered the trial, including 43 on SUBA and 46 on c-itra. We measured PK serum levels of itra and hydroxyl-itra at days 7, 14, and 42 and these data are depicted in Figures 1-3. There were no significant differences in these levels, including combined itra/hydroxyl-itra levels, among the two study arms. AUC for itra and hydroxyl-itra were similar for both arms. AEs as assessed at each study evaluation were also quite similar among the two study arms. Overall, any AE occurred in 74% vs 85% of SUBA and c-itra recipients, respectively (NS). Drug-related AEs occurred in 35% vs 41% of SUBA and itra recipients, respectively (NS). Most common drug-related AEs included cardiovascular (edema and hypertension), nausea and loss of appetite. Combined Itraconazole and Hydroxy-itraconazole Concentration Over Time Conclusion Compared to c-itra, SUBA demonstrates almost identical serum levels despite being dosed at roughly 60% standard dosing for c-itra (130 mg po bid vs 200 mg po bid). SUBA is slightly better tolerated than c-itra, although the specific AEs are similar. Disclosures Peter G. Pappas, MD, Astellas (Research Grant or Support)Cidara (Research Grant or Support)F2G (Consultant)Matinas (Consultant, Scientific Research Study Investigator)Mayne Pharma (Research Grant or Support)Scynexis (Research Grant or Support) Andrej Spec, MD, MSCI, Mayne Pharma (Grant/Research Support) Marisa Miceli, MD, SCYNEXIS, Inc. (Advisor or Review Panel member) George R. R. Thompson III, III, MD, Amplyx (Consultant, Grant/Research Support)Appili (Consultant)Astellas (Consultant, Grant/Research Support)Avir (Grant/Research Support)Cidara (Consultant, Grant/Research Support)F2G (Consultant, Grant/Research Support)Mayne (Consultant, Grant/Research Support)Merck (Scientific Research Study Investigator)Pfizer (Advisor or Review Panel member)

Download Full-text