Randomized Open-label Multicenter Parallel-group Study of Efficacy and Safety of TL-FVP-t vs. Standard of Care Therapy in Patients With Mild to Moderate Coronavirus Disease (SARS-CoV-2/COVID-19)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 168
- 试验地点
- 10
- 主要终点
- Time to clinical improvement
研究概览
简要总结
Randomized open-label multicenter parallel-group study of efficacy and safety of TL-FVP-t vs. standard of care therapy in patients with mild to moderate coronavirus disease (SARS-CoV-2/COVID-19)
详细描述
This was an open label, randomized, controlled, multicenter Phase 3 study of TL-FVP-t in outpatients and inpatients with mild to moderate COVID-19. After stratification by the severity of their disease (mild or moderate), age (18-44 or ≥ 45 years) and CT severity subjects were randomized at a rate of 2:1 to receive either TL-FVP-t + standard concomitant therapy or standard ethiptropic therapy (standard of care - SOC) including standard concomitant therapy. Standard ethiptropic therapy according to MoH of Russian Federation included umifenovir + intranasal recombinant interferon alpha, hydroxichloroquine, or chloroquine.
The dose regimen was the following: TL-FVP-t at a dose of 1800 mg BID on the Day 1 followed by 800 mg BID during the next 9 days. The study included the period of therapy (10 days) and follow-up period (18 days).
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 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Informed consent form signed.
- •Males and females aged 18-60 years;
- •Diagnosis of coronavirus disease caused by SARS-CoV-2 (COVID-19) in a mild or moderate form (without respiratory failure).
- •Duration of infection symptoms shall be no more than 6 days before randomization.
- •SARS-CoV-2 infection should be verified by PCR at the screening.
- •Ability to follow the protocol and fulfill all the clinical study procedures.
- •Ability and willingness of the subjects and their sexual partners with retained childbearing potential to use reliable contraception methods throughout the study and for 3 months after the treatment completion.
- •Willingness not to take alcohol throughout the study.
排除标准
- •Age < 18 and > 60 years.
- •Any etiotropic therapy of coronavirus SARS-CoV-2 (COVID-19) infection prior to the study.
- •Moderate infection with respiratory failure, severe or extremely severe SARS-CoV-2 (COVID-19) disease.
- •Respiratory failure (RR > 30/min, SpO2 ≤ 93 %) or the need for mechanical ventilation at the screening.
- •Decreased level of consciousness (disorientation of place, time and personality), agitation at the screening.
- •Unstable hemodynamics (systolic BP < 100 mm Hg or diastolic BP < 60 mm Hg) found at the screening.
- •Subtotal diffuse ground-glass induration of pulmonary tissue and pulmonary consolidation combined with reticular changes; involvement of ≥ 75 % of lung parenchyma; hydrothorax (CT findings corresponding to ≥ CT-4 according to Department of Health of Moscow guidelines).
- •Presence of comorbidities:
- •moderate or severe chronic obstructive pulmonary disease or asthma;
- •severe chronic cardiovascular disorders (arrhythmia or conduction disorders, implanted pacemaker device, myocardial infarction or unstable angina in the medical history, heart failure);
- •immunocompromised subjects (HIV, cancer, autoimmune diseases, immunodepressant therapy);
- •severe obesity (body mass index [BMI] ≥ 40);
- •diabetes mellitus;
- •chronic renal failure;
- •chronic moderate or severe hepatic disorders.
- •Any of the following abnormal laboratory tests at the screening: AST or ALT level > 2.5 x upper normal level (UNL), platelet count < 50х109/L.
- •Any history findings which, in the investigator's opinion, may complicate the interpretation of the study results or generate an additional risk for the subject due to his/her participation in the study.
- •More than 2 CT diagnostic procedures within the last 6 months prior to randomization (except for chest CT no earlier than 4 days prior to enrollment).
- •The subject takes the products significantly inhibiting CYP28С, and administration those products cannot be interrupted for the study duration.
- •Malabsorption syndrome or another clinically relevant gastrointestinal disease which may affect the study product absorption (uncontrollable vomiting, diarrhea, ulcerative colitis, etc.).
- •Pregnancy or breast-feeding; women with probable pregnancy at the screening, those planning to conceive during the study.
- •Known (from the history) or suspected alcohol or psychotropic drug abuse; medicinal or illicit drug addiction.
- •Mental disorders including those in the medical history.
- •Condition or disease which, according to the investigator or medical monitor, will compromise the subject's safety or affect assessment of the study product safety.
研究组 & 干预措施
TL-FVP-t (favipiravir) Treatment Arm
Day 1: favipiravir 1800 mg BID plus Standard of Care (SOC); Days 2-10: 800 mg BID plus SOC.
干预措施: Favipiravir (Drug)
TL-FVP-t (favipiravir) Treatment Arm
Day 1: favipiravir 1800 mg BID plus Standard of Care (SOC); Days 2-10: 800 mg BID plus SOC.
干预措施: standard concomitant therapy (Drug)
Standard of Care Arm
Standard of Care including etiotropic therapy according to MoH of Russian Federation Recomendations for COVID-19 (umifenovir + intranasal recombinant interferon alpha, or hydroxychloroquine, or chloroquine, or mefloquine in recomended regimen) up to10 days
干预措施: Standard of care (SOC) (Drug)
Standard of Care Arm
Standard of Care including etiotropic therapy according to MoH of Russian Federation Recomendations for COVID-19 (umifenovir + intranasal recombinant interferon alpha, or hydroxychloroquine, or chloroquine, or mefloquine in recomended regimen) up to10 days
干预措施: standard concomitant therapy (Drug)
结局指标
主要结局
Time to clinical improvement
时间窗: through Day 28
To determine the effect of TL-FVP-t vs. SOC on time to clinical improvement. The clinical improvement is defined as reduction on at least 1 score of patient clinical status according to WHO 8-category Ordinal Scale for Clinical Improvement compared to screening
Time to viral clearance
时间窗: through Day 28
To determine the effect of TL-FVP-t vs. SOC on time to viral clearance of SARS-CoV-2 virus as measured by PCR in oropharyngeal sampling
次要结局
- Rate of viral clearance at separate time points(Days 5 and 7)
- Rate of resolution of lung changes on CT(Day 14)
- Rate therapy termination due to ADR(through Day 28)
- Rate of clinical improvement at separate time points(Day 7)
- Time to body temperature normalization(through Day 28)
- Rate of adverse drug reactions (ADR) and serious ADR(through Day 28)
- Rate of severe ADR(through Day 28)