Phase 2, Exploratory, Single Center, Randomized, Open Label, Adaptive Clinical Trial to Compare Safety and Efficacy of Four Different Experimental Drug Regimens to Standard of Care for the Treatment of Symptomatic Outpatients With COVID-19
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 192
- 试验地点
- 1
- 主要终点
- Incidence of SARS-CoV-2 Clearance
研究概览
简要总结
This exploratory study is a randomized, single center, open label study of four different experimental treatment arms versus standard of care for the treatment of SARS-CoV-2 infection in symptomatic outpatients with mild disease at the time of enrollment.
详细描述
This phase 2, exploratory study will be an adaptive, randomized, open label, trial for treatment of individuals in an outpatient settings with mild SARS-CoV-2 infection. The primary outcome is focused on the evaluation of efficacy of the proposed experimental drugs in reducing upper respiratory viral shedding, defined as viral clearance (i.e., negative swab) on Day 7. Key secondary outcomes focus on other measures of viral shedding, safety evaluation, progression to LRTI (defined by resting blood oxygen saturation level [SpO2] <93% sustained for two readings two hours apart and presence of subjective dyspnoea or cough), disease severity, clinical resolution rate, and cumulative incidence of hospitalization or mortality at Day 28.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age from 18 to 65 years of age, inclusive, at the time of signing the informed consent.
- •Willing and able to provide informed consent.
- •Women of reproductive potential must be using a highly effective method of contraception for at least 28 days prior to enrolment and must be able and willing to continue its use throughout the duration of the study.
- •Men must agree to use condoms when engaging in heterosexual sex during the study and for the period up to 91 days after the last dose of study medication. Men who are not randomized to a treatment arm including favipiravir (or another arm identified as having teratogenic potential through semen) will no longer need to adhere to this after randomization.
- •Laboratory confirmed SARS-CoV-2 infection, and any of the following self-reported symptoms within 72 hours prior to randomization: fever or chills, cough, myalgia, sore throat, shortness of breath, or new onset of anosmia or ageusia.
- •Body weight ≥45 kg.
- •Access to reliable video conference, telephone, direct/text messaging, or other device permitting real-time, reliable information transfer.
排除标准
- •Pregnant or lactating women.
- •Known hypersensitivity or specific contraindications to the use of any of the active drugs in the treatment arms, or similar compounds.
- •Signs of respiratory distress prior to randomization, including:
- •respiratory rate >24 breaths/min
- •SpO2 <95% in room air.
- •Resting pulse rate ≥120 beats/min.
- •High likelihood of hospitalization in the opinion of the attending clinician.
- •QTcF >470 msec for females, or >450 msec for males, at screening.
- •Serum potassium <3.5 mmol/L at screening.
- •History of clinically significant cardiovascular disease (including arrhythmias, QT-interval prolongation, torsades de pointes (TdP), history of coronary artery disease with graft or stent procedures/surgery, cardiac failure [class 2 or higher using the New York Heart Association functional classification]).
- •Known chronic kidney disease (Stage IV or receiving dialysis).
- •Known cirrhosis (Child-Pugh Class B or greater).
- •Known macular degeneration, or other known retinal diseases, or 4-aminoquinolone-induced visual impairment.
- •Currently receiving, or recently received (within 60 days prior to randomization) treatment with any of the drugs in the treatment arms.
- •Currently receiving, or recently received (within 30 days prior to randomization) treatment with any antimalarial drugs.
- •Currently on treatment with drugs with known arrhythmogenic potential, or those known to induce significant QT-interval prolongation or TdP, as detailed in Appendix
- •Currently on treatment for tuberculosis (or on treatment with rifampicin for any other indication), or on treatment with a protease inhibitor-based antiretroviral regimen, or efavirenz, or carbamazepine.
- •Inability/unlikely to be in the study area for the duration of the 28 day follow-up period.
- •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 volunteer or the objectives of the study. The Investigator should make this determination in consideration of the volunteer's medical history.
- •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.
- •Participant is judged by the Investigator to be at significant risk of failing to comply with the provisions of the protocol as to cause harm to self or seriously interfere with the validity of the study results.
研究组 & 干预措施
Paracetamol (SOC)
500 mg oral tablets. Two tablets taken at 6-hour intervals as needed, in all treatment arms (in addition to any investigative treatment)
干预措施: Paracetamol (Drug)
Artesunate-amodiaquine (ASAQ)
Fixed dose combination tablets containing 100 mg artesunate and 270 mg amodiaquine. Participants received two tablets once daily for 3 days
干预措施: Artesunate-amodiaquine (Drug)
Pyronaridine-artesunate (PA)
Fixed dose combination tablets containing 180 mg pyronaridine and 60 mg artesunate, given once daily for 3 days. Participants weighing 45 to <65 kg received 3 tablets per dose, those ≥65 kg received 4 tablets per dose
干预措施: Pyronaridine-artesunate (Drug)
Favipiravir plus nitazoxanide (FPV-NTZ)
Free combination of favipiravir 200 mg and 400 mg tablets and nitazoxanide 500 mg tablets. Participants received favipiravir as a loading dose of 1600 mg twice daily for 1 day followed by 600 mg twice daily for 6 days, and nitazoxanide 1000 mg twice daily, with food, for 7 days
干预措施: Favipiravir plus Nitazoxanide (Drug)
SOC plus Sofosbuvir/daclatasvir
Fixed dose combination tablets containing 400 mg sofosbuvir and 60 mg daclatasvir. Participants received 1 tablet once daily for 7 days
干预措施: Sofosbuvir/daclatasvir (Drug)
结局指标
主要结局
Incidence of SARS-CoV-2 Clearance
时间窗: Day 7
次要结局
- LRTI(Day 28)
- Maximum Score on WHO Ordinal Scale for Clinical Improvement During Study Participation(Day 28)
- Incidence of SARS-CoV-2 Clearance(Day 3, 10, 14, 21, 28)
- Time to Clearance of Nasal SARS-CoV-2(Day 0, 3, 7, 10, 14, 21, 28)
- Estimated Viral Load of SARS-CoV-2 Detected by Quantitative RT-PCR(Day 14)
- Poisson Regression for Proportion of Days With Fever After Randomization(Day 28)
- Percentage of Days With Respiratory Symptoms After Randomization(from randomization to end of study (until day 28))
- FLU-PRO Plus Questionnaire Scores and FLU-PRO Plus Global Additional Daily Diary Items Over the First 14 Days(14 days)
- Serious Adverse Events(Day 28)
- Adverse Events(Day 28)
- Related Adverse Events(Day 28)
- Cumulative Incidence of Hospitalization(Day 28)
- Days of Hospitalization(Day 28)
- Cumulative Incidence of Mortality, Measured at Day 28 or Later if Participant is Hospitalized at the Time of Day 28(at Day 28 or later if participant is hospitalized at the time of Day 28 for up to 2 months)