Covid-19 Living Data

Trial NCT04405570
Publication Fischer W, Sci Transl Med (2021) (published paper)
Dates: 2020-06-19 to 2021-01-21
Funding: Mixed (Ridgeback Biotherapeutics, Wayne and Wendy Holman, Merck, Drug Innovations at Emory (DRIVE) LLC, US government)
Conflict of interest: Yes

Methods
	RCT Blinding: double blinding
	Location : Multicenter / USA Follow-up duration (days): 28
Inclusion criteria	Able to provide informed consent prior to initiation of any study procedures ≥18 years of age at Screening Study treatment is expected to begin within ≤168 hours from first symptom onset Ability to swallow pills Documentation of confirmed active SARS-CoV-2 infection, as determined by a molecular test conducted at any US clinic or laboratory that has a Clinical Laboratory Improvement Amendments (CLIA) certification or its equivalent from an NP swab collected ≤96 hours prior to study entry Experiencing at least one of the following SARS-CoV-2 infection symptoms: fever (can be subjective including feeling feverish or having chills) OR signs/symptoms of respiratory illness (including but not limited to upper respiratory congestion, loss of sense of smell or taste, sore throat OR lower respiratory illness - cough, shortness of breath) Agrees to not participate in another interventional clinical trial for the treatment of SARS-CoV-2 during the study period (28 days) unless hospitalized Agrees to not obtain investigational medications outside of the EIDD-2801 study Agrees to the sampling detailed in the schedule of evaluations (SOE) and to comply with study requirements including contraception requirements Female participants of childbearing potential must meet the following criteria to be enrolled: i. Have a negative pregnancy test at Day 1, prior to randomization. ii. Must agree to undergo a follow-up pregnancy test on Study Day 28. iii. Must agree to use at least 2 forms of contraception during the study and for at least 50 days after dosing of the study drug is complete, as discussed with and approved by the investigator, OR Must have an azoospermic partner (vasectomized or due to a to medical cause). Note: azoospermic partner is acceptable provided that the partner is the sole sexual partner of the woman of childbearing potential and the absence of sperm has been confirmed Male participants must refrain from donating sperm during the study and for 100 days after dosing of the study drug is complete Male participants with female partners must have either Surgical sterilization (vasectomy ≥1 month before screening) OR Female partner must be of not be of childbearing potential OR Agree to use 2 forms of contraception during the study and for 100 days after dosing of the study drug is complete, as discussed with and approved by the investigator
Exclusion criteria	Need for hospitalization or immediate medical attention in the clinical opinion of the study investigator Hemoglobin <10 g/dL in men and <9 g/dL in women Platelet count <125,000/L Estimated Glomerular Filtration Rate (eGFR) <60 mL/min/1.73m2 Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≥3x upper limit normal (ULN) History of or current hospitalization for COVID-19 History of significant kidney disease in the opinion of the site investigator History of significant liver disease in the opinion of the site investigator or active Hepatitis B or active Hepatitis C Human immunodeficiency virus (HIV) that is advanced (CD4<200/mm3) and/or on treatment with nucleoside analogues History of known blood dyscrasia Use of therapeutic interventions with possible anti-SARS-CoV-2 activity within 30 days prior to study entry, e.g., remdesivir, lopinavir/ritonavir fixed dose combination, ribavirin, chloroquine, hydroxychloroquine, convalescent plasma, or participation in a clinical trial involving any of these drugs whether for treatment or prophylaxis Receipt of a SARS-CoV-2 vaccination prior to study entry Known allergy/sensitivity or any hypersensitivity to components of EIDD-2801, or its formulation Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements History of recent hemorrhagic cerebrovascular accident (CVA) or major bleed Presence of a condition, that in the opinion of the investigator, would place the subject at increased risk from study participation
Interventions
	Treatment Molnupiravir 200 200 mg orally twice daily for 5 days Molnupiravir 800 mg orally twice daily for 5 days Molnupiravir 400 400 mg orally twice daily for 5 days
	Control Placebo
Participants
	Randomized NR Analyzed 202 participants Molnupiravir 200=23 Placebo=62 Molnupiravir=55 Molnupiravir 400=62
	Characteristics of participants N= 202 Mean age : NR 98 males Severity : Mild: n= 202/ Asymptomatic: n=0 Number of vaccinated participants: NR
Primary outcome
	In the register 1. Virologic Efficacy [ Time Frame: 28 days ]; 2. Number of Participants with any Adverse Events (AEs) as Assessed by Kaplan Meier Approach [ Time Frame: 28 days ]
	In the report Time to viral RNA clearance; Adverse events that were Grade 3 or higher and those that led to early treatment discontinuation
Documents available	Protocol NR Statistical plan NR Data-sharing willing stated in the publication: N
Risk of bias Overall The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review	High
General comment	In addition to the published report, the preprint article, the trial registry (dated May 28 2020) was used for data extraction and risk of bias assessment. The study achieved the target sample size as reported in the registry. There is no change from the trial registration in the intervention and control treatments. The registry primary outcome reflects the reported primary outcome, but timepoints were not specified in the registry. Additional outcomes are reported in the article, including mortality, antibody detection, self-reported health, and symptom duration. This study was updated on the March 2nd, 2022 with data from the published report.