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.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 59
- 试验地点
- 4
- 主要终点
- To evaluate the safety of molnupiravir in adults with mild COVID-19
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None (Participant, Care Provider, Investigator)
盲法说明
Open Label
入排标准
- 年龄范围
- 50 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Able and willing to provide written or electronic informed consent prior to any study-specific procedure.
- •Age ≥50 at the time of signing the informed consent form.
- •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
- •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.
- •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-
- •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.
- •Participant is at high risk for progression to severe COVID-19, this defined as either:
- •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.
- •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.
排除标准
- •Pregnant or breastfeeding women, or women planning/desiring to become pregnant during the 28 days following enrolment into the study.
- •Duration of self-reported symptoms of COVID-19 for more than five days prior to screening.
- •Signs of respiratory distress or severe disease prior to enrolment, including:
- •Inability/unlikely to be in the study area for the duration of the 28-day follow-up period.
- •Inability to tolerate oral medications.
- •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.
- •The volunteer is assessed to be clinically unstable in the Investigator's opinion.
- •Participation in another investigational study involving an investigational product within 30 days, or 5 half-lives, whichever is longer, prior to screening.
- •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.
- •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.
研究组 & 干预措施
Monulpiravir
Eligible participants will be randomised in a 1:1 manner to receive either molnupiravir 800 mg orally approximately 12-hourly for five days or a placebo for the equivalent amount of time.
干预措施: Molnupiravir 200 mg (Drug)
Placebo
Eligible participants will be randomised in a 1:1 manner to receive either molnupiravir 800 mg orally approximately 12-hourly for five days or a placebo for the equivalent amount of time.
干预措施: Molnupiravir 200 mg (Drug)
结局指标
主要结局
To evaluate the safety of molnupiravir in adults with mild COVID-19
时间窗: 29 Days
Self-assessed vital signs to Day 10
To evaluate the effectiveness of molnupiravir compared to placebo in preventing severe disease progression in adults with mild COVID-19
时间窗: 29 Days
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
次要结局
- To describe adherence to a 5-day course of molnupiravir in adults with mild COVID-19(29 Days)
- To describe the utilisation of health care services by adults with mild COVID-19 treated with molnupiravir compared to placebo(29 Days)
- To facilitate same-day COVID-19 diagnosis and treatment initiation in adults with mild COVID-19 and comorbid conditions(29 Days)
- To describe time to symptom resolution in adults with mild COVID-19 treated with molnupiravir compared to placebo(29 Days)
- To evaluate maximum COVID-19 disease severity in adults treated with molnupiravir compared to placebo(29 Days)
- To report the incidence and outcome of pregnancies in female participants who received molnupiravir(Once)
- To assess the tolerability of molnupiravir in adults with mild COVID-19(29 Days)
- To evaluate the relationship between effectiveness of molnupiravir and time between onset of symptoms and initiation of treatment(Day 0, 3, 6, 10, 29)
研究者
Professor Francois Venter
Head: Clinical Research
University of Witwatersrand, South Africa