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 in adult patients with mild COVID-19 at the time of enrolment, who are at risk of progression to severe disease, compared to a placebo.
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 in 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. Approximately 4000 eligible patients will be enrolled and will be randomised in a 1:1 manner to start treatment with either molnupiravir or a placebo on the same day. Patients will record their symptoms (through a self-administered questionnaire) and self-observed vital signs daily for 10 days from the time of enrolment and will be contacted by study team personnel on Days 3, 6 and 10 to monitor their well-being. Adverse event and concomitant medication data will be collected. A final end-of-study follow-up visit will be conducted on Day 29. An independent Data and Safety Monitoring Board (DSMB) will be convened for this study with expertise in COVID-19 or respiratory viruses, and emerging epidemics. The purpose of the DSMB is to monitor the study for safety and operational futility. In addition to the usual, regular, required reporting to SAHPRA, the investigator anticipates that additional reporting will be required by the Clinical Trials Committee, noting the severity of the 3rd and 4th waves, the level of ''breakthrough'' infections in the context of high background comorbidities, and the urgent interest in this class of drugs.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
59
The drug is orally bioavailable (and is indicated for treatment of mild to moderate COVID-19 in adults with a positive SARS-COV-2 diagnostic test and who have at least one risk factor for developing severe illness. The recommended dose is 800 mg (four 200 mg capsules) taken orally 12-hourly for five days, and should be administered as soon as possible after diagnosis of COVID-19 has been made and within five days of symptom onset.
Nelson Mandela Academic Clinical Research Unit (NeMACRU)
Umtata, Eastern Cape, South Africa
Sunnyside Office Park
Johannesburg, Gauteng, South Africa
Nelson R. Mandela School of Medicine 3rd Floor, K-RITH Tower Building
Durban, KwaZulu-Natal, South Africa
The Aurum Institute: Gavin J Churchyard Legacy Centre Klerksdorp Clinical Research Centre
Klerksdorp, North West, South Africa
To evaluate the effectiveness of molnupiravir compared to placebo in preventing severe disease progression in adults with mild COVID-19
Combination of incidence of COVID-19-related hospitalisation (24 hours of care in a hospital or similar acute care facility) and COVID-19-related mortality to Day 29
Time frame: 29 Days
To evaluate the safety of molnupiravir in adults with mild COVID-19
Adverse events (including serious adverse events and adverse drug reactions)
Time frame: 29 Days
To evaluate the safety of molnupiravir in adults with mild COVID-19
Self-assessed vital signs to Day 10
Time frame: 29 Days
To facilitate same-day COVID-19 diagnosis and treatment initiation in adults with mild COVID-19 and comorbid conditions
Proportion of enrolled patients for whom diagnosis and same day treatment initiation was facilitated through use of a LumiraDx™ rapid antigen test
Time frame: 29 Days
To assess the tolerability of molnupiravir in adults with mild COVID-19
Severity of adverse events
Time frame: 29 Days
To assess the tolerability of molnupiravir in adults with mild COVID-19
Adverse event-related study drug discontinuations
Time frame: 29 Days
To describe time to symptom resolution in adults with mild COVID-19 treated with molnupiravir compared to placebo
Time to sustained resolution of symptoms as reported in the Flu-PRO© Plus
Time frame: 29 Days
To evaluate maximum COVID-19 disease severity in adults treated with molnupiravir compared to placebo
Maximum score on the WHO Clinical Progression Scale from Day 1 to Day 29
Time frame: 29 Days
To evaluate the relationship between effectiveness of molnupiravir and time between onset of symptoms and initiation of treatment
Number of days from symptom onset to initiation of treatment
Time frame: 29 Days
To evaluate the relationship between effectiveness of molnupiravir and time between onset of symptoms and initiation of treatment
Incidence of hospitalisation (24 hours of care in a hospital or similar acute care facility) and/or death to Day 29 in patients with co-morbid conditions
Time frame: 29 Days
To evaluate the relationship between effectiveness of molnupiravir and time between onset of symptoms and initiation of treatment
Time to sustained resolution of symptoms as reported in the Flu-PRO Plus
Time frame: Day 1 to Day 10 and Day 29
To evaluate the relationship between effectiveness of molnupiravir and time between onset of symptoms and initiation of treatment
Maximum score on the WHO Clinical Progression Scale from Day 1 to Day 29. On a scale of 0 to 10 (0 being uninfected and 10 being worse/death)
Time frame: Day 0, 3, 6, 10, 29
To describe adherence to a 5-day course of molnupiravir in adults with mild COVID-19
Proportion of patients completing the course of molnupiravir as prescribed
Time frame: 29 Days
To describe the utilisation of health care services by adults with mild COVID-19 treated with molnupiravir compared to placebo
Rate of hospital, emergency facility, clinic, health care practitioner or home visits to Day 29
Time frame: 29 Days
To report the incidence and outcome of pregnancies in female participants who received molnupiravir
Incidence of pregnancy in female participants to Day 29
Time frame: 29 Days
To report the incidence and outcome of pregnancies in female participants who received molnupiravir
20-week gestational age ultrasound findings
Time frame: Once
To report the incidence and outcome of pregnancies in female participants who received molnupiravir
Pregnancy complications
Time frame: Throughout the pregnancy
To report the incidence and outcome of pregnancies in female participants who received molnupiravir
Pregnancy outcome
Time frame: Once
To report the incidence and outcome of pregnancies in female participants who received molnupiravir
Infant wellbeing to three months of age
Time frame: Once
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