Evaluation of Safety and Clinical Efficacy of AZVUDINE in COVID-19 Patients (SARS-CoV-2 Infected): Phase III, Randomized, Double-blind, PLACEBO Controlled Trial
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 180
- 试验地点
- 1
- 主要终点
- Evaluation of clinical improvement of AZVUDINE (FNC) in COVID-19 treatment
研究概览
简要总结
Estimated number of participants: 342 participants with COVID-19 Design: Phase III, single-center, randomized, double-blind, parallel, placebo-controlled clinical study.
In December 2021, there was a drop in the number of hospitalizations and the cases of COPD, tuberculosis and HIV associated with COVID-19, which are outside the inclusion criteria of this study. After the initial data of the study, there was a discussion with Anvisa and the size of the sample calculation was revised by amendment 4 (180 participants), and the methodology of statistical analysis for a new sample calculation was "a formula for sample calculation for superiority studies using proportions, according to the book do Chow et al (Chow, S.-C., Shao, J., Wang, H., &Lokhnygina, Y. Eds. 2017. Sample Size Calculations in Clinical Research: Third Edition, Chapman and Hall/CRC). Thus, Anvisa concluded that the adjustments are in accordance with the agency's guidelines, approving E4, which was later also approved by the Ethics Committee.
详细描述
Hypothesis:
AZVUDINE has therapeutic potential and safety profile for the treatment of patients infected with SARS-CoV-2.
Goals:
Primary objective • To assess the efficacy and safety of AZVUDINE (FNC) in relation to placebo, in patients infected with SARS-COV-2 in moderate to severe stage;
Secondary objective
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Individuals aged 18 or over, regardless of gender;
- •Patients hospitalized in moderate to severe stages in line with the Ministry of Health classification;
- •Positive diagnosis for SARS-CoV-2 by molecular amplification of the virus in RT-PCR diagnosed from a respiratory sample (nasopharynx, oropharyngeal, lower respiratory tract [eg, sputum]) collected <96 hours before randomization;
- •Time of onset of symptoms and inclusion ≤ 14 days;
- •Internation within 48 hours after inclusion in the study;
- •Follow-up availability during the study period;
- •Voluntary membership to participate in the study and signing the Informed Consent Form.
排除标准
- •Patients known or suspected of being sensitive to AZVUDINE or excipients (inactive ingredients: microcrystalline cellulose, hydrated lactose, polyvinylpyrrolidone K30, croscarmellose sodium, magnesium stearate);
- •Patients diagnosed with pneumonia caused by other pathogens;
- •Patients with liver disease (total bilirubin ≥2 times above the normal limit, ALT / TGP and AST / TGO ≥5 times above the normal limit)
- •Patients with renal failure (glomerular filtration rate ≤60mL / min / 1.73 m2) or are receiving continuous renal replacement therapy, hemodialysis or peritoneal dialysis;
- •Individuals with malabsorption syndrome, or other conditions that affect gastrointestinal absorption, and circumstances in which patients need intravenous nutrition, or cannot take drugs orally or nasogastrically;
- •Pregnant or lactating women, or women with the potential to become pregnant during the study period and within 6 months after the end of administration;
- •Patients already included in other clinical trials;
- •Patient under treatment for HIV;
- •Patients being treated with other antivirals (eg lopinavir / ritonavir, remdesivir, umifenovir / arbidol, favipiravir, interferon-α)
- •Patients undergoing treatment with monoclonal antibodies (eg tocilizumab and sarilumab / kevzara);
- •Patients who are on a clinical treatment plan that includes the concomitant administration of any other experimental treatment or off-label use of drugs already on the market (eg hydroxychloroquine sulfate;
- •Patients who require invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) at the time of randomization;
- •Any clinically significant medical condition or medical history that, in the investigator's opinion, might discourage participation in the study.
研究组 & 干预措施
Arm AZVUDINE
Experimental:
AZVUDINE 1mg tablet,
Interventions:
AZVUDINE 1mg tablet, 5 tablets QD + standard treatment for up to 14 days
干预措施: AZVUDINE (Drug)
Arm Placebo
Control:
AZVUDINE placebo,
Interventions:
AZVUDINE placebo, 5 tablets QD + standard treatment for up to 14 days
干预措施: AZVUDINE placebo (Drug)
结局指标
主要结局
Evaluation of clinical improvement of AZVUDINE (FNC) in COVID-19 treatment
时间窗: Day 1 to Day 15
Rate of participants who reduced at least one level of the Clinical Progression Ordinal Scale category compared to the enrollment status (WHO, Jun/2020)
次要结局
- Clinical cure outcome rate(Day 1 to Day 15)
- Assessment of inflammatory biochemical markers (Reactive C Protein, erythrocyte sedimentation rate, and Procalcitonin)(Day 1 to Day 60)
- Assessment of immunological function biochemical markers (IL-6, IgG, IgM, IgA, and complement factor C3 and C4)(Day 1 to Day 60)
- Assessment of liver function biochemical markers (AST/TGO, ALT/TGP, ALP, GGT, BIL total, and direct BIL)(Day 1 to Day 60)
- Evaluation of the number of cycles for the detection of SARS-CoV-2 viral load by RT-PCR and application of the standard curve for calculating viral load(Day 1 to Day 15)
- Analysis of the relationship between the calculated viral load and the clinical evolution of the participants in the experimental group (FNC) and the PLACEBO group(Day 1 to Day 28)
- Time for improvement of pulmonary condition by imaging exams during treatment(Day 1 to Day 28)
- Evaluation of pulmonary condition by imaging exams during treatment(Day 1 to Day 28)
- Time for clinical improvement of respiratory signs and symptoms(Day 1 to Day 28)
- Recovery of body temperature(Day 1 to Day 28)
- Clinical improvement of diarrhea, myalgia fatigue and other symptoms(Day 1 to Day 28)
- Evaluation of time to negative conversion of SARS-CoV-2 viral load by RT-PCR(Day 1 to Day 28)
- Assessment of renal function biochemical markers (serum creatinine and calculated glomerular filtration rate)(Day 1 to Day 60)
- Assessment of clinical improvement of respiratory signs and symptoms(Day 1 to Day 28)
- Time for normalization of O2 saturation(Day 1 to Day 28)
- Respiratory rate evaluation(Day 1 to Day 28)
- Frequency of supplemental oxygenation or non-invasive ventilation(Day 1 to Day 28)
- Assessment of hospitalization time(Day 1 to Day 28)
- Frequency of invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO(Day 1 to Day 28)
- Proportion of moderate cases that progressed to severe cases(Day 1 to Day 28)
- Evaluation of drug interaction events frequency(Day 1 to Day 28)
- Evaluation of drug interaction events intensity(Day 1 to Day 28)
- Assessment of adverse events frequency(Day 1 to Day 28)
- Assessment of adverse events intensity(Day 1 to Day 28)
- Assessment of unexpected adverse events frequency(Day 1 to Day 28)
- Assessment of unexpected adverse events intensity(Day 1 to Day 28)
- Assessment of serious adverse events frequency(Day 1 to Day 28)
- Assessment of serious adverse events intensity(Day 1 to Day 28)
- Overall mortality rate(Day 1 to Day 28)
- Evaluation of the tolerability of azvudine in the 5 mg regimen orally QD up to 14 days(Day 1 to Day 28)
- Assessment of adherence of azvudine in the 5 mg regimen orally QD up to 14 days(Day 1 to Day 28)
- Time of use of azvudine in the 5 mg regimen orally QD up to 14 days(Day 1 to Day 28)