595. Letermovir (LTV) for Secondary Cytomegalovirus (CMV) Prevention in High Risk Hematopoietic Cell Transplant (HCT) Recipients: Interim Results of a Single Center, Open Label Study

Abstract Background Letermovir (LTV) is effective for prevention (ppx) of primary clinically significant CMV infection (csCMVi) in the first 100 days after hematopoietic cell transplant (HCT). Data on LTV for secondary ppx is limited. We report on the efficacy and safety of LTV administered for 14 weeks as secondary CMV ppx. Methods Patients (pts) enrolled in an open label study of LTV (ClinicalTrials.gov identifier: NCT04017962) from August 2019 through February 2021 were analyzed. Key eligibility criteria were: CMV high risk (receipt of mismatched and/or T-cell depleted HCT and/or graft versus host disease (GVHD) requiring systemic immunosuppressants) AND prior csCMVi with either undetectable CMV (≤ 136 IU/mL) or ≥ 2 consecutive values < 300 IU/mL at enrollment. Pts with breakthrough csCMVi on LTV or history of LTV resistance were excluded. LTV was administered for 14 weeks or csCMVi whichever occurred first. The study duration was 24 weeks. CMV was monitored per standards of care. The primary endpoint was csCMVi by week 14. Secondary endpoints were csCMVi by week 24, LTV resistance, CMV end-organ disease (EOD) and adverse events (AE) at least possibly related to LTV. Results Of 20 pts analyzed, the median age was 58 years (interquartile range [IQR] 46-63); 17 (85%) pts were CMV seropositive, 7 (35%) received mismatched HCT (haploidentical 3, cord blood 3; mismatched unrelated 1), 9 (45%) received CD34 selected allograft and 9 (45%) had GVHD at enrollment. Fourteen (70%) pts had received prior LTV. The median time from HCT to enrollment was 156 (IQR 37-244) and 55 (IQR 40-69) days for pts with and without prior LTV, respectively (P=0.16). CMV at enrollment was < 136IU/mL for 8 (40%) pts. By week 14, 4 (20%) pts developed csCMVi at median 48 days (range 40-66). Resistance testing performed in 3 of the 4 pts, identified LTV resistance mutations in 2 pts. There were no AEs related to LTV, and none developed EOD. Two pts developed csCMVi in the follow up phase. Three pts died during follow up (due to relapse, treatment related toxicity and GVHD), and four pts are in follow up. Conclusion LTV secondary prophylaxis was safe and prevented recurrent csCMVi in 80% of high risk patients, including patients with prior LTV exposure. Our data supports the utility of LTV for secondary CMV prevention following HCT. Disclosures Boglarka Gyurkocza, MD, Actinium Pharma, Inc. (Grant/Research Support, Research Grant or Support) Genovefa Papanicolaou, MD, ADMA biologics and Siemens Healthineers (Consultant, Other Financial or Material Support)AlloVir (Consultant, Other Financial or Material Support)Amplyx (Scientific Research Study Investigator, Other Financial or Material Support)Astellas (Consultant, Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support, Other Financial or Material Support)Behring (Consultant, Other Financial or Material Support)Chimerix (Consultant, Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support, Other Financial or Material Support)Cidara (Consultant, Other Financial or Material Support)Merck & Co (Consultant, Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support, Other Financial or Material Support)Partners Therapeutics (Consultant, Other Financial or Material Support)Shionogi (Consultant, Other Financial or Material Support)Shire/Takeda (Consultant, Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support, Other Financial or Material Support) Genovefa Papanicolaou, MD, allovir (Individual(s) Involved: Self): Consultant; amplyx (Individual(s) Involved: Self): Consultant; behring (Individual(s) Involved: Self): Consultant; Merck&Co (Individual(s) Involved: Self): Consultant, Investigator and received funding and consulting fees from Merck, Chimerix, Shire and Astellas, Research Grant or Support; octapharma (Individual(s) Involved: Self): Consultant; Partners Therapeutics (Individual(s) Involved: Self): Consultant; takeda (Individual(s) Involved: Self): Consultant, Scientific Research Study Investigator

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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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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)

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

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.1642 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S806-S807

Author(s):

Joshua A Hill ◽

Roger Paredes ◽

Carlos Vaca ◽

Jorge Mera ◽

Brandon J Webb ◽

...

Keyword(s):

High Risk ◽

Research Study ◽

Scientific Research ◽

Panel Member ◽

Research Support ◽

Review Panel ◽

Double Blind ◽

Material Support ◽

Double Blind Placebo ◽

Study Investigator

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)

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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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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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1514. Mortality and Readmission in Adults during the First Year Following Hospitalization for Community-Acquired Pneumonia in the US

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1695 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S760-S760

Author(s):

Reiko Sato ◽

Derek Weycker ◽

Melody Shaff ◽

Ahuva Hanau ◽

Alexander Lonshteyn ◽

...

Keyword(s):

At Risk ◽

High Risk ◽

Hospital Readmission ◽

Research Study ◽

Scientific Research ◽

Research Support ◽

Post Discharge ◽

Study Investigator ◽

Comorbidity Profile ◽

Research Grant

Abstract Background Increasing evidence suggests that the impact of community-acquired pneumonia (CAP) extends beyond discharge from the hospital and the acute phase of illness. We sought to characterize mortality and hospital readmission across the adult age span and spectrum of comorbidities. Methods A retrospective cohort design and data from Optum’s de-identified Integrated Claims-Clinical dataset (2009-2018) were employed. Study population comprised all adults who, between 1.1.2013 and 12.31.2017, had ≥ 1 acute-care hospitalization for CAP; each qualifying CAP hospitalization separated by ≥ 365 days was included as a unique observation in analyses. Study outcomes included acute-care hospital readmission for any reason and death for any reason. Hospital readmission was ascertained during the 360-day period following discharge from the CAP hospitalization; death was ascertained during the CAP hospitalization as well as during the same 360-day period. Cumulative rates of mortality and readmission were summarized for all patients as well as subgroups defined on age and comorbidity profile (i.e., healthy, at-risk, high-risk). Results Study population totaled 37,006 patients who contributed 38,809 CAP hospitalizations; mean age was 71 years, 51% were female, and 88% had an at-risk (33%) or high-risk (55%) condition. Hospital readmission was 12.5% during the 30-day post-discharge period, and 42.3% during the 360-day post-discharge period. Mortality was 3.5% in hospital, 8.2% from admission to 30 days post-discharge, and 17.7% from admission to 360 days post-discharge. Mortality rates increased with age and severity of comorbidity profile; readmission rates were highest for persons aged 65-74 years and high-risk persons. Rates of readmission and mortality among adults hospitalized for CAP Conclusion All-cause mortality up to 1 year following hospital admission for CAP was substantial, and was associated with increasing age and worsening comorbidity profile. Both readmission and mortality were greater at all ages in high-risk and at-risk groups compared with their healthy counterparts. Strategies that prevent pneumonia and/or the pathophysiologic changes that follow CAP, especially among individuals with comorbid conditions, have the potential to reduce morbidity and mortality following CAP as well as healthcare costs associated with readmission. Disclosures Reiko Sato, PhD, Pfizer, Inc (Employee, Shareholder) Derek Weycker, PhD, Pfizer Inc. (Consultant, Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support) Melody Shaff, BA, Pfizer, Inc. (Consultant, Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support) Ahuva Hanau, BS, Pfizer, Inc. (Consultant, Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support) Alexander Lonshteyn, PhD, Pfizer, Inc. (Consultant, Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support) Stephen I. Pelton, MD, Merck vaccine (Consultant, Grant/Research Support)Pfizer (Consultant, Grant/Research Support)Sanofi Pasteur (Consultant, Other Financial or Material Support, DSMB)Seqirus Vaccine Ltd. (Consultant)

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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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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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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)

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