Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202203593113347 Date of Approval: 30/03/2022
Trial Status: Retrospective registration - This trial was registered after enrolment of the first participant
TRIAL DESCRIPTION
Public title MKK4482-013: MK-4482 Phase 3 Study for Prevention of COVID-19 in Adults
Official scientific title MK4482-013: A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of MK-4482 for the Prevention of COVID-19 (Laboratory-confirmed SARS-CoV-2 Infection With Symptoms) in Adults Residing With a Person With COVID-19
Brief summary describing the background and objectives of the trial This is a Phase 3, randomized, placebo-controlled, double-blind, multi-site study (MOVe-AHEAD) to evaluate the efficacy and safety of MOV to prevent COVID-19 in participants 2:18 years of age residing with an individual (no age requirement) with COVID-19 (defined as the index case). Antivirals for prevention of COVID-19 are urgently needed during this unprecedented global pandemic. This randomized, placebo-controlled, double­ blind, superiority study is designed to evaluate the efficacy and safety of MOV compared with placebo for the prevention of COVID-19 in household contacts of an individual with COVID-19, in accordance with available regulatory guidance [Food and Drug Administration 2021].Primary Objectives: 1. To evaluate the efficacy of molnupiravir (MOV) compared with 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. Hypothesis: MOV is superior to placebo for 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. 2. To evaluate the safety and tolerability of MOV compared with placebo. Secondary Objectives: 1. 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 COVID-19. 2. 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. 3.To evaluate prevention of viral transmission through Day 14 for MOV compared with placebo in participants with undetectable SARS CoV-2
Type of trial RCT
Acronym (If the trial has an acronym then please provide) MOVe AHEAD
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied COVID-19
Purpose of the trial Treatment: Drugs
Anticipated trial start date 16/08/2021
Actual trial start date 16/09/2021
Anticipated date of last follow up 31/08/2022
Actual Last follow-up date 16/11/2022
Anticipated target sample size (number of participants) 150
Actual target sample size (number of participants)
Recruitment status Completed
Publication URL www.msd.co.za
Secondary Ids Issuing authority/Trial register
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Parallel: different groups receive different interventions at same time during study Randomised Simple randomization using a randomization table created by a computer software program Central randomisation by phone/fax Masking/blinding used Care giver/Provider
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Control Group Placebo 0mg, once every twelve hours orally Participants will receive the doses for a period of 5 days, totaling 10 doses There are currently no agents approved for the prevention of COVID-19 to serve as an active comparator; therefore, placebo will be used. 75 Placebo
Experimental Group MK4482 Molnupiravir MOV (MK-4482): 800mg, once every 12 hours, orally Participants will receive MOV for 5 days, totalling 10 doses The MOV dose for this Phase 3 study (800 mg MOV Q12H for 5 days) was selected based on interim data from other studies evaluating MOV for treatment as well as the totality of available safety, virology, PK, and clinical data from the MOV programme. The eDMC review of unblinded interim data from MK-4482-001 and MK-4482-002 concluded that there were no safety signals seen at any dose, and no dose-limiting toxicity was observed at the highest dose (800 mg). Furthermore, MOV has been generally well tolerated in other studies in the MOV program at all doses studied with no dose­ limiting toxicity observed at the highest dose (800 mg). Virology data from interim data in the MOV programme (MK-4482-001, MK-4482- 002, and MK-4482-006) show that treatment with MOV reduces the SARS- CoV-2 viral load compared with placebo (based on change from baseline, slope of decline, and greater proportion of participants with a viral load below the limit of quantitation within 15 or 29 days) in non- hospitalised participants enrolled in MK-4482-002 and participants with symptom onset :55 days in both MK-4482-001 and MK- 4482-002. Based on the totality of the observed safety profile and virologic data in the MOV program, and trends in clinical efficacy in MK-4482-002, the 800 mg Q12H dose was selected as the dose for further evaluation in Phase 3. 75
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
1.The participant is a household contact of an index case. An index case is a person with documented COVID-19 (laboratory-confirmed SARS-CoV-2 infection with symptoms case) and must have:a) A first detectable SARS-CoV-2 test result from a sample collected ≤5 days prior to randomization of the participant(s),AND b)At least 1 of the following symptoms attributable to COVID-19: fever ≥38.0ºC,chills,cough,sore throat, shortness of breath or difficulty breathing with exertion,fatigue,nasal congestion,runny nose,headache,muscle or body aches,nausea,vomiting,diarrhea,loss of taste,or loss of smell, with symptom onset no earlier than 5 days prior to randomization of the participant(s).2.The participant does not have confirmed or suspected COVID-19.3.The participant is willing and able to take oral medication.4.The participant is male or female ≥18 years of age,at the time of providing documented informed consent.5. There are no contraceptive requirements for male participants per protocol.However,where applicable,male participants are only eligible to participate if they agree to follow local labelling (or local ethics or regulatory authority requirement) regardingcontraception.6. A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:•Is not a WOCBP OR •Is a WOCBP and:- Uses a contraceptive method that is highly effective (a low user dependency method OR a user dependent hormonal method in combination with barrier method), or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis),during the intervention period and for at least 4 days after the last dose of study intervention.7.The participant’s index case (or legally acceptable representative of the index case) has provided documented informed consent/assent for the collection of COVID-19 documentation requirements.8. Documented informed consent. 1. The participant has a prior history of laboratory-confirmed SARS-CoV-2 infection (with or without symptoms), within 6 months prior to randomization.2.The participant has either of the following conditions:-HIV with a recent viral load >50 copies/mL (regardless of CD4 count) or an AIDS defining illness in the past 6 months.Note: Participants with HIV may only be enrolled if on a stable antiretroviral therapy regimen.3.The participant has a history of HBV or HCV infection with any of the following:Cirrhosis,End-stage liver disease,Hepatocellular carcinoma, AST and/or ALT >3X upper limit of normal at screening.4.The participant has hypersensitivity or other contraindication to any of the components of the study interventions as determined by the investigator. 5.The participant has any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant or that could prevent, limit, or confound the protocol-specified assessments including but not limited to participants with conditions that could limit gastrointestinal absorption of capsule contents.6.The participant has received, is taking, or is anticipated to require any prohibited therapies. 7. The participant has received a COVID-19 vaccine with the first dose 7 days or more prior to randomization.8.The participant is unwilling to abstain from participating in another interventional clinical study through Day 29 with an investigational compound or device, including those for COVID-19 therapeutics.9.The participant is living in a household of more than 10 people. 10. Is or has an immediate family member (eg, spouse, parent/legal guardian, sibling, or child) who is investigational site or Sponsor staff directly involved with this study. 80 and over: 80+ Year,Adult: 19 Year-44 Year,Aged: 65+ Year(s),Middle Aged: 45 Year(s)-64 Year(s) 18 Year(s) 90 Year(s) Both
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 03/12/2021 University of the Witwatersrand Human Research Ethics Committee Medical
Ethics Committee Address
Street address City Postal code Country
31 Princess Wales Terrace Johannesburg 2041 South Africa
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 21/09/2021 Pharma Ethics
Ethics Committee Address
Street address City Postal code Country
123 Amcor Road Centurion 0157 South Africa
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
No 02/03/2022 Scientific and Ethics Review Unit
Ethics Committee Address
Street address City Postal code Country
P.O. Box 54840 00200 House number 8, KEMRI Headquarters. Off Mbagathi road, Nairobi, Kenya, 00200 P.O. Box 54840 00200 Nairobi 00200 Kenya
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 31/03/2022 Scientific and Ethics Review Unit
Ethics Committee Address
Street address City Postal code Country
P.O. Box 54840 00200 House number 8, KEMRI Headquarters. Off Mbagathi road, Nairobi, Kenya, 00200 P.O. Box 54840 00200 Nairobi 00200 Kenya
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 17/03/2022 University of Cape Town Health Research Ethics Committee
Ethics Committee Address
Street address City Postal code Country
Anzio Road, Observatory Cape Town 7925 South Africa
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome The primary efficacy endpoint is the proportion of participants developing COVID-19 (laboratory­ confirmed SARS-CoV-2 infection with symptoms) through Day 14 Day 14
Secondary Outcome Proportion of participants developing COVID-19 through Day 29 ? Proportion of participants with undetectable SARS-CoV-2 in baseline NP swabs developing COVID-19 through Day 14? Proportion of participants with undetectable SARS-CoV-2 in baseline NP swabs having viral transmission through Day 14 Day 14 and Day 29
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
KENYA MEDICAL RESEARCH INSTITUTE KEMRI CENTER FOR MICROBIOLOGY RESEARCH Agoi Street Kisumu 40100 Kenya
CLINICAL HIV RESEARCH UNIT THEMBA LETHU CLINIC HELEN JOSEPH HOSPITAL Perth Road Johannesburg 2041 South Africa
IATROS INTERNATIONAL Brandwag Bloemfontein 9300 South Africa
ENHANCING CARE FOUNDATION Sidmouth Avenue Durban 4052 South Africa
BE PART RESEARCH PTY LTD 4 Madikane Street Paarl 7626 South Africa
JONGAIE RESEARCH 551 Nkomo Street Pretoria 0183 South Africa
MZANSI ETHICAL RESEARCH CENTRE 184 Cowen Ntuli Street Middelburg 1055 South Africa
LIMPOPO CLINICAL RESEARCH INITIATIVE 11 Van Der Bijl Street Thabazimbi 0380 South Africa
DESMOND TUTU HEALTH FOUNDATION MASIPHUMULELE RESEARCH OFFICE Guinea Fowl Rd Cape Town 7975 South Africa
TASK APPLIED SCIENCE TASK CLINICAL RESEARCH CENTRE 187-189 Voortrekker Road Cape Town 7500 South Africa
CLINICAL TRIAL SYSTEMS Baviaanspoort Road Pretoria 0186 South Africa
QHAKAZA MBOKODO RESEARCH CLINIC 15 Parklane Mkhamba Gardens Ladysmith 3370 South Africa
DJW NAVORSING 70 Shannon Road Krugersdorp 1739 South Africa
HEALTH EMPORIUM Corner Market and Church Street Midrand 1685 South Africa
DR NK GOUNDEN MEDI CENTRE 7 Wingen Walk Shallcross 4093 South Africa
REIMED REIGER PARK 56 Arthur Hobbs Street Boksburg 1459 South Africa
RIGHT TO CARE RESEARCH ESIZAYO Corner Malibongwe Drive and Tennesse Avenue Randburg 2087 South Africa
DR PRAKASH JUGNUNDAN PRIVATE PRACTICE 283 Quarry Road East Durban 4091 South Africa
PARTNERS IN HEALTH RESEARCH AND DEVELOPMENT PHRD Section 9, OUA Road, Thika Town Nairobi 00202 Kenya
CENTER FOR CLINICAL RESEARCH CCR KENYA MEDICAL RESEARCH INSTITUTE Mbagathi Road, Off Raila Odinga Way Nairobi 00200 Kenya
ZINAKEKELE MEDICAL CENTRE 2457 Moloto South, Block 6, Ward 3 Kwamhlanga 1022 South Africa
FUNDING SOURCES
Name of source Street address City Postal code Country
MSD Pty Ltd 16th Road Midrand 1685 South Africa
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor MSD Pty Ltd 16th Road Midrand 1685 South Africa Commercial Sector/Industry
COLLABORATORS
Name Street address City Postal code Country
CONTACT PEOPLE
Role Name Email Phone Street address
Public Enquiries Zoe Nell zoe.nell@merck.com 27116553307 16th Road
City Postal code Country Position/Affiliation
Midrand 1685 South Africa Clinical Research Director
Role Name Email Phone Street address
Scientific Enquiries MS Rassool mrassool@witshealth.co.za +27112768800 Perth Road
City Postal code Country Position/Affiliation
Johannesburg 2041 South Africa National Principal Investigator
Role Name Email Phone Street address
Principal Investigator RS Rassool mrassool@witshealth.co.za +27112768800 Perth Road
City Postal code Country Position/Affiliation
Johannesburg 2041 South Africa Principal Investigator
Role Name Email Phone Street address
Principal Investigator N Fourie nyda@iatros.co.za +27514440037 20 Captain Proctor Street
City Postal code Country Position/Affiliation
Bloemfontein 9300 South Africa Principal Investigator
Role Name Email Phone Street address
Principal Investigator R Mngqibisa rosie@ecarefoundation.com +27312611093 Sidmouth Avenue
City Postal code Country Position/Affiliation
Durban 4052 South Africa Principal Investigator
Role Name Email Phone Street address
Principal Investigator E Hellstrom pi@bepart.co.za +27218683990 4 Madikane Street
City Postal code Country Position/Affiliation
Paarl 7626 South Africa Principal Investigator
Role Name Email Phone Street address
Principal Investigator DM de Jong douwe@lantic.net +27123275546 551 Nkomo Street
City Postal code Country Position/Affiliation
Pretoria 0183 South Africa Principal Investigator
Role Name Email Phone Street address
Principal Investigator FG Petrick fgpetrick@merc.za.net +27132825218 184 Cowen Ntuli Street
City Postal code Country Position/Affiliation
Middelburg 1055 South Africa Principal Investigator
Role Name Email Phone Street address
Principal Investigator LF Fouche leon.fouche@iafrica.com +27147771939 11 Van Der Bijl Street
City Postal code Country Position/Affiliation
Thabazimbi 0380 South Africa Principal Investigator
Role Name Email Phone Street address
Principal Investigator KM Gill katherine.gill@hiv-research.org.za +27217853121 Guinea Fowl Rd
City Postal code Country Position/Affiliation
Cape Town 7975 South Africa Principal Investigator
Role Name Email Phone Street address
Principal Investigator C Holmgren dr.chantelle@task.org.za +2721103606 187-189 Voortrekker Road
City Postal code Country Position/Affiliation
Cape Town 7500 South Africa Principal Investigator
Role Name Email Phone Street address
Principal Investigator MA Fulat muhammed.fulat@ct-system.com +27128001451 Baviaanspoort Road
City Postal code Country Position/Affiliation
Pretoria 0186 South Africa Principal Investigator
Role Name Email Phone Street address
Principal Investigator P Jugnundan Prakash@iafrica.com +27312093141 283 Quarry Road East
City Postal code Country Position/Affiliation
Durban 4091 South Africa Principal Investigator
Role Name Email Phone Street address
Principal Investigator PL Kotze plkotze@gmail.com +27366312372 15 Parklane Mkhamba Gardens
City Postal code Country Position/Affiliation
Ladysmith 3370 South Africa Principal Investigator
Role Name Email Phone Street address
Principal Investigator JC Jurgens jacojuhl@gmail.com +27829071002 70 Shannon Road
City Postal code Country Position/Affiliation
Krugersdorp 1739 South Africa Principal Investigator
Role Name Email Phone Street address
Principal Investigator A Jacovides andrewjacovides@gmail.com +27113152512 Corner Market and Church Street
City Postal code Country Position/Affiliation
Midrand 1685 South Africa Principal Investigator
Role Name Email Phone Street address
Principal Investigator NK Gounden drgounden@ion.co.za +27314092494 7 Wingen Walk
City Postal code Country Position/Affiliation
Shallcross 4093 South Africa Principal Investigator
Role Name Email Phone Street address
Principal Investigator AC Wilhase acwilhase@gmail.com +27119104968 56 Arthur Hobbs Street
City Postal code Country Position/Affiliation
Boksburg 1459 South Africa Principal Investigator
Role Name Email Phone Street address
Principal Investigator K Mellet kmellet@gmail.com +27104936950 Corner Malibongwe Drive and Tennesse Avenue
City Postal code Country Position/Affiliation
Randburg 2087 South Africa Principal Investigator
Role Name Email Phone Street address
Principal Investigator EA Bukusi ebukusi@kemri.org +27733617503 614 Agoi Street
City Postal code Country Position/Affiliation
Kisumu 40100 Kenya Principal Investigator
Role Name Email Phone Street address
Principal Investigator N Mugo rwamba@uw.edu +254733629665 Partners in Health Research and Development and Center for Clinical Research CCR, Kenya Medical Research Institute KEMRI
City Postal code Country Position/Affiliation
Nairobi 00202 Kenya Principal Investigator
Role Name Email Phone Street address
Principal Investigator K Ngure kngure@pipsthika.org +254722362219 Section 9, OUA Road, Thika Town
City Postal code Country Position/Affiliation
Nairobi 00202 Kenya Co Principal Investigator
Role Name Email Phone Street address
Principal Investigator B Njoroge bnjoroge@kemri.go.ke +254722800693 Mbagathi Road, Off Raila Odinga Way
City Postal code Country Position/Affiliation
Nairobi 00200 Kenya Co Principal Investigator
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes MSD is fully committed to supporting the EFPIA and PhRMA guiding principles on data sharing, including the principle of providing qualified scientific researchers access to anonymized participant-level data and full clinical study reports (CSRs) from MSD’s clinical trials to conduct legitimate scientific research. We are also fully participating in the Institutes of Medicine (IOM) global effort to develop principles for responsible sharing of clinical trial data. Scope of Data: MSD will provide access to participant-level data and CSRs from clinical trials performed by MSD for which results are posted on the clinicaltrials.gov registry (dating back to September 2007) for products or indications that have been approved by regulators in the US and EU. In general, data will be made available for request approximately 18 months after clinical trial completion. Data from phase I trials in healthy volunteers and consumer health care studies are out of scope for this procedure. Plan and Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf Clinical Study Report 18 months after study completion Data Sharing Agreement: Before access to clinical trial data is provided, the researcher must enter into a standard data sharing agreement with MSD. The data sharing agreement commits the researcher to use the data only for the stated research purpose and to not disclose the data to third parties. This is in line with data privacy legislation. In addition, researchers are expected to commit to transparency in the publication of their work. Anonymization of Data:Protecting the privacy of clinical trial participants is an important obligation of sponsors who conduct clinical trials. Therefore, MSD will take appropriate measures, including anonymization of data, to ensure that participant privacy is safeguarded. Data Access: MSD will provide researchers with access to anonymized participant-level data needed to address the specific research question consistent with the requirements noted here. If a request for a full CSR is approved, MSD will provide researchers the CSR in a redacted form that is consistent with the need to protect participant privacy and confidential commercial information.
URL Results Available Results Summary Result Posting Date First Journal Publication Date
http://engagezone.msd.com/ds_documentation.php No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information