Current declaration by the WHO on 11 March 2020 that COVID-19 a disease that is caused by a virus known as SARS-CoV-2, as a global pandemic. Over 170 million confirmed SARS-CoV-2infections with more than 3.5 million deaths have been reported worldwide. A drug known as Molnupiravir (MOV) which has antiviral activity against a range of viruses including coronaviruses is being developed as a drug taken orally to prevent COVID-19 in individuals >18years with no symptoms but living with a person who has been tested and confirmed to have COVID-19 with symptoms. The drug MOV has been shown to work in preventing duplication of numerous family of viruses.

The main aim of this study is to find out if this drug can prevent COVID-19 and if it is safe and well tolerated when compared with an inactive drug for the prevention of laboratory-confirmed COVID-19 through Day 14 in participants (regardless of baseline viral test result) who do not have confirmed or suspected COVID-19 at the time of screening and randomization and are residing with an individual with COVID-19.

Background:

COVID-19, a disease resulting from SARS-CoV-2 infection, was declared a global pandemic by the WHO on 11-MAR-2020. As of early December 2021, more than 170 million confirmed cases of SARS-CoV-2 infection and over 3.5 million COVID-19-related deaths have been reported globally. Molnupiravir (MOV) is a novel ribonucleoside analog prodrug with broad-spectrum antiviral activity against a range of RNA viruses, including coronaviruses. MOV is being developed as an oral prophylactic for COVID-19 (laboratory-confirmed SARS-CoV-2 infection with symptoms) in initially asymptomatic individuals’ ≥18 years of age residing with a person with COVID-19.

Justification:

The constant mutations leading to SARS-CoV-2 variants that have been associated with gradual increase in cases and hospitalizations has brought about high unmet medical need for new, effective therapies and prophylactics. MOV has been shown to inhibit replication of viral pathogens from multiple RNA virus families in vitro, including the highly pathogenic coronaviruses (SARS-CoV-2, MERS-CoV), as well as influenza virus, RSV, filoviruses, flaviviruses, chikungunya virus, and alphaviruses.

Objectives:  Objectives of this study will be evaluated in participants ≥18 years of age who do not have confirmed or suspected COVID-19 at the time of screening and randomization and are residing with an individual (of any age) with COVID-19 (laboratory-confirmed SARS-CoV-2 infection with symptoms), defined as the index case. The primary objective of this study is to evaluate the efficacy, safety and tolerability of Molnupiravir (MOV) compared with placebo for the prevention of laboratory-confirmed COVID-19 through Day 14 in participants (regardless of baseline viral test result) who do not have confirmed or suspected COVID-19 at the time of screening and randomization and are residing with an individual with COVID19. These will be measured by laboratory-confirmed SARS-CoV-2 infection with symptoms and adverse events and adverse events leading to discontinuation of the study intervention. The secondary objectives of this study are: 1) To evaluate the efficacy of MOV compared with placebo for the prevention of laboratory confirmed COVID-19 through Day 14 in participants with undetectable SARS-CoV-2 in baseline nasopharyngeal (NP) swabs as measured by laboratory confirmed SARS-CoV-2 infection with symptoms; 2) To evaluate the efficacy of MOV compared with placebo for the prevention of laboratory-confirmed COVID-19 through Day 29 in participants who do not have confirmed or suspected COVID-19 at the time of screening and randomization and are residing with an individual with COVID19 as measured by laboratory confirmed SARS-CoV-2 infection with symptoms; and 3) To evaluate prevention of viral transmission through Day 14 for MOV compared with placebo in participants with undetectable SARS-CoV-2 in baseline NP swabs as measured by laboratory confirmed SARS-CoV-2 RNA.

Methods:

This is a Phase 3, randomized, placebo-controlled, double-blind, multi-site study to evaluate the efficacy and safety of MOV to prevent COVID-19 in participants ≥18 years of age residing with an individual (no age requirement) with COVID-19 (defined as the index case). Eligible participants who do not have confirmed or suspected COVID-19 at the time of screening and randomization will be randomized within 5 days of both the time of sample collection for the index case’s first positive SARS-CoV-2 test result and time of onset of the index case’s COVID-19 symptoms. Approximately 1332 adult participants who are household contacts of index COVID-19 cases will be randomized in a 1:1 ratio to receive either blinded MOV or blinded placebo. Index cases will not be randomized to receive intervention in the study.

Nature of results expected:

For our primary objectives, we hypothesize that MOV will be superior to placebo for the prevention of laboratory confirmed COVID-19 through Day 14 in participants who do not have confirmed or suspected COVID-19 at the time of screening and randomization and are residing with an individual with COVID-19.  For our main secondary objective, we hypothesize that MOV will be superior to placebo for the prevention of laboratory confirmed COVID-19 through Day 14 in participants with undetectable SARSCoV-2 in baseline nasopharyngeal (NP) swabs.