Effect of Molnupiravir on Mild COVID-19 in High-risk Adults

This is a Multi-centre, Double-blind, Phase 3 Study to Observe the Effectiveness, Safety, and Tolerability of Molnupiravir 800 mg Administered 12-hourly for Five Days to Adult Patients With Mild COVID-19 at the Time of Enrolment Who Are at Risk of Progression to Severe Disease, Compared to a Placebo. Patients With Recent Onset of COVID-19 Symptoms Will be Screened to Assess Eligibility for Enrolment. Confirmation of SARS-CoV-2 Infection Will be Performed Through Rapid Antigen Detection Using the LumiraDx Point of Care Diagnostic Platform.

This study is testing if the medication molnupiravir can help high-risk adults with mild COVID-19 feel better and recover faster.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 4000 (estimated)
• Ages: 50 Years and up
• Sex: All
• Sponsor: University of Witwatersrand, South Africa (Academic / other)
• Locations: 4 sites (Umtata, Eastern Cape and 3 other locations)
• Trial ID: NCT05459532 on ClinicalTrials.gov

What this trial studies

This phase 3 clinical trial evaluates the effectiveness, safety, and tolerability of molnupiravir, administered at 800 mg every 12 hours for five days, in high-risk adult outpatients with mild COVID-19. Participants will be randomly assigned to receive either the medication or a placebo, and their symptoms and vital signs will be monitored daily for 10 days. The study aims to enroll approximately 4000 patients, with a follow-up visit on Day 29 to assess outcomes. An independent Data and Safety Monitoring Board will oversee the study to ensure safety and efficacy.

Who should consider this trial

Good fit: Ideal candidates are adults aged 50 and older with recent onset COVID-19 symptoms and at risk of severe disease.

Not a fit: Patients with mild COVID-19 symptoms who are not at risk of progression to severe disease may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly reduce the risk of mild COVID-19 patients progressing to severe disease.

How similar studies have performed: Other studies have shown promising results with antiviral treatments for COVID-19, making this approach both relevant and potentially impactful.

Eligibility criteria

Inclusion Criteria:

1. Able and willing to provide written or electronic informed consent prior to any study-specific procedure.
2. Age ≥50 at the time of signing the informed consent form.
3. Women of reproductive potential must have a negative pregnancy test at screening and be using a highly effective method of contraception. Highly effective methods of contraception
4. A male participant must wear a condom when engaging in any activity that allows for passage of ejaculate to another while taking the investigational product. Male participants should also be advised of the benefit for a female partner to use a highly effective method of contraception as condom may break or leak.
5. Self-reported symptoms of COVID-19 with onset no more than five days prior to screening informed consent including at least one of, fever or chills, cough, sore throat, rhinorrhoea or rhinitis or sinusitis, shortness of breath, headache, myalgia, new onset anosmia or ageusia, nausea, diarrhoea, or extreme fatigue, or other symptoms recognized in local and international guidelines as typical of mild COVID-19.
6. SARS-CoV-2 infection confirmed through a positive LumiraDx rapid antigen test on the day of screening or a positive RT-PCR within two days prior to screening.
7. Participant is at high risk for progression to severe COVID-19, this defined as either:

   1. Age ≥50 with at least one of the following background or medical conditions: diabetes mellitus, obesity (BMI 30 kg/m2), hypertension, HIV, active or previous TB.
   2. Age ≥65
8. Participant agrees to comply with study procedures, including the completion of a daily diary for 10 days from the time of enrolment, and to be available for study contacts and visits.

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Exclusion Criteria:

1. Pregnant or breastfeeding women, or women planning/desiring to become pregnant during the 28 days following enrolment into the study.
2. Duration of self-reported symptoms of COVID-19 for more than five days prior to screening.
3. Signs of respiratory distress or severe disease prior to enrolment, including:
4. Inability/unlikely to be in the study area for the duration of the 28-day follow-up period.
5. Inability to tolerate oral medications.
6. Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of drugs, or which may jeopardize the safety of the patient or the objectives of the study. The Investigator should make this determination in consideration of the volunteer's medical history.
7. The volunteer is assessed to be clinically unstable in the Investigator's opinion.
8. Participation in another investigational study involving an investigational product within 30 days, or 5 half-lives, whichever is longer, prior to screening.
9. Personnel (e.g., investigator, sub-investigator, research assistant, pharmacist, study coordinator or anyone mentioned in the delegation log) directly involved in the conduct of the study.
10. Any physical, mental, or social condition, drug/alcohol use, history of illness or laboratory abnormality that, in the Investigator's judgment, might jeopardise the safety of the patient in the context of this study, or might interfere with study procedures or the ability of the subject to adhere to and complete the study. The Investigator should make this determination in consideration of the volunteer's medical history.

Where this trial is running

Umtata, Eastern Cape and 3 other locations

• Nelson Mandela Academic Clinical Research Unit (NeMACRU) — Umtata, Eastern Cape, South Africa (Recruiting)
• Sunnyside Office Park — Johannesburg, Gauteng, South Africa (Recruiting)
• Nelson R. Mandela School of Medicine 3rd Floor, K-RITH Tower Building — Durban, Kwa-Zulu Natal, South Africa (Recruiting)
• The Aurum Institute: Gavin J Churchyard Legacy Centre Klerksdorp Clinical Research Centre — Klerksdorp, North West, South Africa (Recruiting)

Study contacts

• Study coordinator: Bukani X Dyariwe

Conditions COVID-19