An Adaptive, Multicenter, Randomized, Open-label, Comparative Clinical Study to Assess Efficacy and Safety of Favipiravir in Hospitalized Patients With COVID-19
试验速览
- 阶段
- 2 期
- 发起方
- Chromis LLC
- 入组人数
- 330
- 试验地点
- 22
- 主要终点
- Rate of viral elimination by Day 10 [pilot stage, dose selection]
研究概览
简要总结
The study is Phase II/III and consists of pilot and pivotal stages. The objective of the pilot stage is to conduct a preliminary assessment of the efficacy and safety of Favipiravir, and to select the optimal dosing regimen to study during the pivotal stage. The objective of the pivotal stage is to assess the efficacy and safety of Favipiravir compared with the Standard of care (SOC) in hospitalized patients with moderate to severe COVID-19 pneumonia.
详细描述
At the pilot stage: upon signing the informed consent form and screening, 60 eligible patients with polymerase chain reaction (PCR) confirmed COVID-19 pneumonia are randomized at a 1:1:1 ratio to receive either Favipiravir 1600 mg twice a day (BID) on Day 1 followed by 600 mg BID on Days 2-14 (1600/600 mg), or Favipiravir 1800 mg BID on Day 1 followed by 800 mg BID on Days 2-14 (1800/800 mg), or SOC.
At the pivotal stage: additional 270 eligible patients are randomized at a 1:1 ratio to receive either Favipiravir (the dose regimen depends of the subject's weight) or SOC.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed Patient Information Sheet and Informed Consent form to participate in the study.
- •Men and women aged 18 years and older.
- •Patients hospitalized with a diagnosis of COVID-
- •The diagnosis of COVID-19 was confirmed by positive reverse transcription polymerase chain reaction (RT-PCR) test for SARS-CoV-2, performed no earlier than 7 days before hospitalization or at screening.
- •Moderate severity of COVID-19 with pneumonia with at least 1 of the following symptoms:
- •Fever above 38 °C;
- •Shortness of breath during physical exertion;
- •C reactive protein (CRP) of blood serum > 10 mg/l;
- •SpO2 < 95%
- •The capability of oral drug administration.
- •The patients' consent to use adequate contraception methods during the study (condom with spermicide) and for 3 months following completion.
排除标准
- •Severe type of disease, with at least one of the following criteria:
- •Frequency of breath > 35 per minute, which does not decrease after the body temperature drops to normal or subfebrile values;
- •Blood oxygen saturation (SpO2) < 90% at rest;
- •Partial pressure of oxygen in arterial blood (PaO2) < 60 mm Hg;
- •Oxygenation index (RaO2/FiO2) ≤ 200 mm Hg;
- •Partial pressure of CO2 in arterial blood (PaCO2) < 60 mm Hg;
- •Septic shock.
- •Patients treated with lopinavir/ritonavir, ribavirin, arbidol, chloroquine, hydroxychloroquine, mefloquine, favipiravir within 7 days prior to screening.
- •Severe cardiovascular diseases currently or 6 months prior to randomization, including: New York Heart Association (NYHA) Class III or IV chronic heart failure, clinically significant ventricular arrhythmias (ventricular tachycardia, ventricular fibrillation), unstable angina, myocardial infarction, heart and coronary vessel surgery, significant valvular heart disease, uncontrolled arterial hypertension with systolic blood pressure > 180 mm Hg and diastolic blood pressure > 110 mm Hg, pulmonary embolism or deep vein thrombosis.
- •Severe chronic renal impairment (GFR < 30 ml / min) or continuous renal replacement therapy, hemodialysis or peritoneal dialysis.
- •A history of cirrhosis or an increase in alanine aminotransferase (ALT) and / or aspartate aminotransferase (AST) > 5 times × upper limit of normal (ULN).
- •Severe diseases of the central nervous system, including seizures in history or conditions that may lead to their development; stroke or transient ischemic attack within 12 months prior to screening; head injuries or loss of consciousness within 12 months prior to screening; a brain tumor.
- •Significant uncontrolled concomitant disease, e.g. neurological, renal, hepatic, endocrinological or gastrointestinal disorder which according to the Investigator, could prevent the patient from participating in the study
- •Malignancies that require chemotherapy within 6 months prior to screening.
- •Known HIV infection
- •Hypersensitivity to any component of the study drug.
- •Participation in other clinical studies or taking other study drugs within 28 days prior to screening.
- •Pregnant or lactating women or women planning to get pregnant during the clinical study; women of child-bearing potential (including non-sterilized by surgical means and during the post-menopause period less than 2 years) who do not use adequate contraception methods.
- •Inability to read or write, unwillingness to understand and follow procedures of study protocol, as well as any other concomitant medical or serious mental conditions that make the patient unfit to participate in the study, limit the legality of obtaining informed consent or can affect patient's ability to participate in the study.
研究组 & 干预措施
Favipiravir, lower dose (pilot stage)
1600mg BID on the 1st day followed by 600mg BID for 13 days
干预措施: Favipiravir (Drug)
Favipiravir, higher dose (pilot stage)
1800mg BID on the 1st day followed by 800mg BID for 13 days
干预措施: Favipiravir (Drug)
Standard of care (pilot stage)
Based on approved clinical recommendations for treatment of COVID-19 in the Russian Federation (but not Favipiravir). Might include hydroxychloroquine, chloroquine, lopinavir/ritonavir or other recommended schemes.
干预措施: Standard of Care (Drug)
Favipiravir, selected dose (pivotal stage)
The dose will be selected based on pilot study results.
干预措施: Favipiravir (Drug)
Standard of care (pivotal stage)
Based on approved clinical recommendations for treatment of COVID-19 in the Russian Federation (but not Favipiravir). Might include hydroxychloroquine, chloroquine, lopinavir/ritonavir or other recommended schemes.
干预措施: Standard of Care (Drug)
结局指标
主要结局
Rate of viral elimination by Day 10 [pilot stage, dose selection]
时间窗: 10 Days
Percent of patients with undetectable SARS-CoV-2 RNA level on Day 10
Time to viral elimination [pivotal stage]
时间窗: 28 Days
Median time to reach undetectable SARS-CoV-2 RNA level
Time to clinical improvement [pivotal stage]
时间窗: 28 Days
Median time reach clinical improvement (2 points of the Ordinal Scale for Clinical Improvement) or discharge from the hospital
次要结局
- Duration of oxygen therapy(28 Days)
- Rate of viral elimination(Days 3, 5, 7, 9, and 11)
- Rate of transfer to the intensive care unit(28 days)
- Area under the plasma concentration versus time curve (AUC0-t)(10 days)
- Time to normalization of clinical symptoms(28 Days)
- Change in the level of lung damage according to CT(Days 15, 22, and 29)
- Rate of the use of non-invasive lung ventilation(28 days)
- Mortality(28 days)
- Time to peak plasma concentration (Tmax)(Day 1)
- Trough plasma concentration (Ctrough)(10 days)
- Rate of the use of mechanical ventilation(28 days)
- Peak plasma concentration (Cmax)(Day 1)