Trial Outcomes & Findings for Study of MK-4482 for Prevention of Coronavirus Disease 2019 (COVID-19) in Adults (MK-4482-013) (NCT NCT04939428)

NCT ID: NCT04939428

Last Updated: 2024-09-26

Results Overview

Percentage of participants who had undetectable SARS-CoV-2 in baseline NP swabs and developed COVID-19 (laboratory-confirmed SARS-CoV-2 infection with symptoms) through Day 14 were reported.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

2441 participants

Primary outcome timeframe

Day 14

Results posted on

2024-09-26

Participant Flow

Only eligible participants without confirmed or suspected coronavirus disease 2019 (COVID-19) were enrolled within a 5-day period of the index case's first positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test result and COVID-19 symptoms onset.

Index cases were enrolled but did not receive study treatment upon randomization and with the exception of characteristics collected at baseline and optional exploratory swab collection, no other data were collected.Index participants were not followed up for survival and no mortality data were collected per protocol.Index cases were not included in protocol specified outcome measure data collection.

Participant milestones

Participant milestones
Measure
Molnupiravir
Participants were treated with molnupiravir 800 mg every 12 hours (Q12H) on Days 1 to 5.
Placebo
Participants were given placebo Q12H on Days 1 to 5.
Index Participants
Index case was a participant with documented COVID-19 infection. Index participants were enrolled but did not receive study intervention. Index participants resided in the same household as enrolled participants who received study intervention.
Overall Study
STARTED
768
771
902
Overall Study
Treated
763
765
0
Overall Study
COMPLETED
750
751
0
Overall Study
NOT COMPLETED
18
20
902

Reasons for withdrawal

Reasons for withdrawal
Measure
Molnupiravir
Participants were treated with molnupiravir 800 mg every 12 hours (Q12H) on Days 1 to 5.
Placebo
Participants were given placebo Q12H on Days 1 to 5.
Index Participants
Index case was a participant with documented COVID-19 infection. Index participants were enrolled but did not receive study intervention. Index participants resided in the same household as enrolled participants who received study intervention.
Overall Study
Death
0
1
0
Overall Study
Lost to Follow-up
0
5
0
Overall Study
Physician Decision
1
0
0
Overall Study
Randomized By Mistake Without Study Treatment
1
0
0
Overall Study
Withdrawal by Subject
10
11
0
Overall Study
Unkown
6
3
0
Overall Study
Discotinued per protocol
0
0
902

Baseline Characteristics

Per protocol study specific charachteristics data was not collected for index cases as no study specific assessments were done.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Molnupiravir
n=768 Participants
Participants were treated with molnupiravir 800 mg every 12 hours (Q12H) on Days 1 to 5.
Placebo
n=771 Participants
Participants were given placebo Q12H on Days 1 to 5.
Index Participants
n=902 Participants
Index case was a participant with documented COVID-19 infection. Index participants were enrolled but did not receive study intervention. Index participants resided in the same household as enrolled participants who received study intervention.
Total
n=2441 Participants
Total of all reporting groups
Age, Continuous
37.0 years
STANDARD_DEVIATION 15.6 • n=768 Participants
37.0 years
STANDARD_DEVIATION 15.5 • n=771 Participants
38.0 years
STANDARD_DEVIATION 17.7 • n=902 Participants
37.0 years
STANDARD_DEVIATION 15.6 • n=2441 Participants
Age, Customized
<18
0 Participants
n=768 Participants
0 Participants
n=771 Participants
76 Participants
n=902 Participants
76 Participants
n=2441 Participants
Age, Customized
Adults (18-49 years)
563 Participants
n=768 Participants
568 Participants
n=771 Participants
548 Participants
n=902 Participants
1679 Participants
n=2441 Participants
Age, Customized
From 50 to 64 years
144 Participants
n=768 Participants
141 Participants
n=771 Participants
199 Participants
n=902 Participants
484 Participants
n=2441 Participants
Age, Customized
From 65 to 74 years
35 Participants
n=768 Participants
44 Participants
n=771 Participants
54 Participants
n=902 Participants
133 Participants
n=2441 Participants
Age, Customized
>=75 years
26 Participants
n=768 Participants
18 Participants
n=771 Participants
25 Participants
n=902 Participants
69 Participants
n=2441 Participants
Sex: Female, Male
Female
366 Participants
n=768 Participants
342 Participants
n=771 Participants
541 Participants
n=902 Participants
1249 Participants
n=2441 Participants
Sex: Female, Male
Male
402 Participants
n=768 Participants
429 Participants
n=771 Participants
361 Participants
n=902 Participants
1192 Participants
n=2441 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
323 Participants
n=768 Participants
340 Participants
n=771 Participants
341 Participants
n=902 Participants
1004 Participants
n=2441 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
445 Participants
n=768 Participants
430 Participants
n=771 Participants
552 Participants
n=902 Participants
1427 Participants
n=2441 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants
n=768 Participants
1 Participants
n=771 Participants
9 Participants
n=902 Participants
10 Participants
n=2441 Participants
Race (NIH/OMB)
American Indian or Alaska Native
85 Participants
n=768 Participants
90 Participants
n=771 Participants
80 Participants
n=902 Participants
255 Participants
n=2441 Participants
Race (NIH/OMB)
Asian
48 Participants
n=768 Participants
40 Participants
n=771 Participants
62 Participants
n=902 Participants
150 Participants
n=2441 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
1 Participants
n=768 Participants
4 Participants
n=771 Participants
2 Participants
n=902 Participants
7 Participants
n=2441 Participants
Race (NIH/OMB)
Black or African American
62 Participants
n=768 Participants
60 Participants
n=771 Participants
77 Participants
n=902 Participants
199 Participants
n=2441 Participants
Race (NIH/OMB)
White
453 Participants
n=768 Participants
446 Participants
n=771 Participants
552 Participants
n=902 Participants
1451 Participants
n=2441 Participants
Race (NIH/OMB)
More than one race
119 Participants
n=768 Participants
129 Participants
n=771 Participants
128 Participants
n=902 Participants
376 Participants
n=2441 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants
n=768 Participants
2 Participants
n=771 Participants
1 Participants
n=902 Participants
3 Participants
n=2441 Participants
Stratification Factor at Randomization Collected via IRT: Household Size
<=3
269 Participants
n=768 Participants • Per protocol study specific charachteristics data was not collected for index cases as no study specific assessments were done.
271 Participants
n=771 Participants • Per protocol study specific charachteristics data was not collected for index cases as no study specific assessments were done.
0 Participants
Per protocol study specific charachteristics data was not collected for index cases as no study specific assessments were done.
540 Participants
n=1539 Participants • Per protocol study specific charachteristics data was not collected for index cases as no study specific assessments were done.
Stratification Factor at Randomization Collected via IRT: Household Size
>=3
499 Participants
n=768 Participants • Per protocol study specific charachteristics data was not collected for index cases as no study specific assessments were done.
500 Participants
n=771 Participants • Per protocol study specific charachteristics data was not collected for index cases as no study specific assessments were done.
0 Participants
Per protocol study specific charachteristics data was not collected for index cases as no study specific assessments were done.
999 Participants
n=1539 Participants • Per protocol study specific charachteristics data was not collected for index cases as no study specific assessments were done.
Stratification Factor at Randomization Collected via IRT: Age Group
<=60
680 Participants
n=768 Participants • Per protocol study specific charachteristics data was not collected for index cases as no study specific assessments were done.
680 Participants
n=771 Participants • Per protocol study specific charachteristics data was not collected for index cases as no study specific assessments were done.
0 Participants
Per protocol study specific charachteristics data was not collected for index cases as no study specific assessments were done.
1360 Participants
n=1539 Participants • Per protocol study specific charachteristics data was not collected for index cases as no study specific assessments were done.
Stratification Factor at Randomization Collected via IRT: Age Group
>=60
88 Participants
n=768 Participants • Per protocol study specific charachteristics data was not collected for index cases as no study specific assessments were done.
91 Participants
n=771 Participants • Per protocol study specific charachteristics data was not collected for index cases as no study specific assessments were done.
0 Participants
Per protocol study specific charachteristics data was not collected for index cases as no study specific assessments were done.
179 Participants
n=1539 Participants • Per protocol study specific charachteristics data was not collected for index cases as no study specific assessments were done.

PRIMARY outcome

Timeframe: Day 14

Population: Efficacy analysis was conducted on the mITT (modified intent to treat) population consisting of all randomized participants who received at least 1 dose of study intervention. Index participants were not included in OM analysis per protocol.

Percentage of participants who had undetectable SARS-CoV-2 in baseline NP swabs and developed COVID-19 (laboratory-confirmed SARS-CoV-2 infection with symptoms) through Day 14 were reported.

Outcome measures

Outcome measures
Measure
Molnupiravir
n=630 Participants
Participants were treated with molnupiravir 800 mg every 12 hours (Q12H) on Days 1 to 5.
Placebo
n=634 Participants
Participants were given placebo Q12H on Days 1 to 5.
Percentage of Participants Who Had Undetectable SARS-CoV-2 in Baseline Nasopharyngeal (NP) Swabs and Developed COVID-19 (Laboratory-Confirmed SARS-CoV-2 Infection With Symptoms) Through Day 14
41 Percentage of Participants
54 Percentage of Participants

PRIMARY outcome

Timeframe: 29 days

Population: Safety Analyses was conducted in the APaT population, which consists of all randomized participants who received at least 1 dose of study intervention. Index participants were not included in OM analysis per protocol.

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.

Outcome measures

Outcome measures
Measure
Molnupiravir
n=763 Participants
Participants were treated with molnupiravir 800 mg every 12 hours (Q12H) on Days 1 to 5.
Placebo
n=765 Participants
Participants were given placebo Q12H on Days 1 to 5.
Percentage of Participants With ≥1 Adverse Event
94 Participants
105 Participants

PRIMARY outcome

Timeframe: Up to 5 days

Population: Safety Analyses was conducted in the APaT population, which consists of all randomized participants who received at least 1 dose of study intervention. Index participants were not included in OM analysis per protocol.

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.

Outcome measures

Outcome measures
Measure
Molnupiravir
n=763 Participants
Participants were treated with molnupiravir 800 mg every 12 hours (Q12H) on Days 1 to 5.
Placebo
n=765 Participants
Participants were given placebo Q12H on Days 1 to 5.
Percentage of Participants Discontinuing From Study Therapy Due to AE
3 Participants
1 Participants

SECONDARY outcome

Timeframe: Up to Day 14

Population: Index participants were not included in OM analysis per protocol.

Participants who experienced targeted symptoms of COVID-19 (e.g., cough, sore throat) and had NP swabs tested for SARS-CoV-2 using reverse-transcription polymerase chain reaction (RT-PCR).Efficacy analysis was conducted on the mITT (modified intent to treat) population consisting of all randomized participants who received at least 1 dose of study intervention.

Outcome measures

Outcome measures
Measure
Molnupiravir
n=763 Participants
Participants were treated with molnupiravir 800 mg every 12 hours (Q12H) on Days 1 to 5.
Placebo
n=764 Participants
Participants were given placebo Q12H on Days 1 to 5.
Percentage of Participants (Regardless of SARS-CoV-2 in Baseline NP Swabs) Who Developed COVID-19 (Laboratory-Confirmed SARS-CoV-2 Infection With Symptoms) Through Day 14
78 Participants
103 Participants

SECONDARY outcome

Timeframe: Up to Day 29

Population: Index participants were not included in OM analysis per protocol.

Participants who experienced targeted symptoms of COVID-19 (e.g., cough, sore throat) and had NP swabs tested for SARS-CoV-2 using RT-PCR. The efficacy analysis population was the mITT (modified intent to treat) population consisting of all randomized participants who received at least 1 dose of study intervention.

Outcome measures

Outcome measures
Measure
Molnupiravir
n=630 Participants
Participants were treated with molnupiravir 800 mg every 12 hours (Q12H) on Days 1 to 5.
Placebo
n=634 Participants
Participants were given placebo Q12H on Days 1 to 5.
Percentage of Participants Who Had Undetectable SARS-CoV-2 in Baseline NP Swabs and Developed COVID-19 (Laboratory-Confirmed SARS-CoV-2 Infection With Symptoms) Through Day 29
51 Participants
65 Participants

SECONDARY outcome

Timeframe: Up to Day 14

Population: Index participants were not included in OM analysis per protocol.

All participants had NP swabs collected at screening and through Day 14 to test for SARS-CoV-2 using RT-PCR. Efficacy analysis was conducted on the mITT (modified intent to treat) population consisting of all randomized participants who received at least 1 dose of study intervention.

Outcome measures

Outcome measures
Measure
Molnupiravir
n=572 Participants
Participants were treated with molnupiravir 800 mg every 12 hours (Q12H) on Days 1 to 5.
Placebo
n=589 Participants
Participants were given placebo Q12H on Days 1 to 5.
Percentage of Participants Who Had Undetectable SARS-CoV-2 in Baseline NP Swabs and Developed Detectable SARS-CoV-2 in NP Swabs on or Before Day 14
65 Participants
85 Participants

SECONDARY outcome

Timeframe: Up to Day 14

Population: Index participants were not included in OM analysis per protocol.

Participants who experienced targeted symptoms of COVID-19 (e.g., cough, sore throat) and had NP swabs tested for SARS-CoV-2 using RT-PCR. Efficacy analysis was conducted on the mITT (modified intent to treat) population consisting of all randomized participants who received at least 1 dose of study intervention.

Outcome measures

Outcome measures
Measure
Molnupiravir
n=114 Participants
Participants were treated with molnupiravir 800 mg every 12 hours (Q12H) on Days 1 to 5.
Placebo
n=114 Participants
Participants were given placebo Q12H on Days 1 to 5.
Percentage of Participants Who Had Detectable SARS-CoV-2 in Baseline NP Swabs and Developed COVID-19 (Laboratory-confirmed SARS-CoV-2 Infection With Symptoms) Through Day 14
35 Participants
47 Participants

Adverse Events

MK-4482

Serious events: 3 serious events
Other events: 0 other events
Deaths: 0 deaths

Placebo

Serious events: 2 serious events
Other events: 0 other events
Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure
MK-4482
n=763 participants at risk
Participants were treated with molnupiravir 800 mg every 12 hours (Q12H) on Days 1 to 5.
Placebo
n=765 participants at risk
Participants were given placebo Q12H on Days 1 to 5.
Cardiac disorders
Acute myocardial infarction
0.00%
0/763 • Up to Day 29
All cause mortality (ACM) was analyzed in all randomized participants.Safety Analyses was conducted in all-participants-as-treated (APaT) population, which consisted of all randomized participants who received at least 1 dose of study intervention. Per protocol all-cause mortality and AE information was not collected for index cases.
0.13%
1/765 • Number of events 1 • Up to Day 29
All cause mortality (ACM) was analyzed in all randomized participants.Safety Analyses was conducted in all-participants-as-treated (APaT) population, which consisted of all randomized participants who received at least 1 dose of study intervention. Per protocol all-cause mortality and AE information was not collected for index cases.
Infections and infestations
COVID-19 pneumonia
0.26%
2/763 • Number of events 2 • Up to Day 29
All cause mortality (ACM) was analyzed in all randomized participants.Safety Analyses was conducted in all-participants-as-treated (APaT) population, which consisted of all randomized participants who received at least 1 dose of study intervention. Per protocol all-cause mortality and AE information was not collected for index cases.
0.13%
1/765 • Number of events 1 • Up to Day 29
All cause mortality (ACM) was analyzed in all randomized participants.Safety Analyses was conducted in all-participants-as-treated (APaT) population, which consisted of all randomized participants who received at least 1 dose of study intervention. Per protocol all-cause mortality and AE information was not collected for index cases.
Injury, poisoning and procedural complications
Femur fracture
0.13%
1/763 • Number of events 1 • Up to Day 29
All cause mortality (ACM) was analyzed in all randomized participants.Safety Analyses was conducted in all-participants-as-treated (APaT) population, which consisted of all randomized participants who received at least 1 dose of study intervention. Per protocol all-cause mortality and AE information was not collected for index cases.
0.00%
0/765 • Up to Day 29
All cause mortality (ACM) was analyzed in all randomized participants.Safety Analyses was conducted in all-participants-as-treated (APaT) population, which consisted of all randomized participants who received at least 1 dose of study intervention. Per protocol all-cause mortality and AE information was not collected for index cases.

Other adverse events

Adverse event data not reported

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme LLC

Phone: 1-800-672-6372

Results disclosure agreements

  • Principal investigator is a sponsor employee If publication activity is not directed by the Sponsor, the investigator agrees to submit all manuscripts or abstracts to the Sponsor before submission. This allows the Sponsor to protect proprietary information and to provide comments.
  • Publication restrictions are in place

Restriction type: OTHER