A Multi-centre, Double-blind, Randomised, Placebo-controlled, Trial to Assess the Efficacy and Safety of Amizon® Max, Manufactured by Farmak JSC, in Combination With Basic Treatment, in Subjects With Moderate Covid-19, Which is Caused by the SARS-CoV-2 Virus
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 592
- 试验地点
- 13
- 主要终点
- Efficacy - Time from day of randomization to an improvement of at least two points (from the status at randomization) on severity rating (SR) scale in days
研究概览
简要总结
Adult female and male patients, hospitalized with Covid-19 infection (confirmed by reverse transcription polymerase chain reaction [RT-PCR]), will be screened for participation in this prospective, multi-center, double-blind, randomised, placebo-controlled trial.
Enrolled patients will be randomized (1:1) into 2 treatment groups: Group 1 will receive the active treatment with Amizon® Max (international nonproprietary name enisamium iodide), one capsule (each containing 500 mg of enisamium iodide) 4 times daily every 6 hours for 7 days; patients in treatment Group 2 will receive a matching placebo capsule, 4 times daily every 6 hours for 7 days. Patient observation and follow-up are planned for 29 days, unless discharged before Day 29.
The effect of treatment on Covid-19 will be evaluated by time from day of randomization to an increase of at least two points (from the status at randomization) on the severity rating scale (SR), the Time to Clinical Recovery (TTCR) of main Covid-19 symptoms / complications and the Sum of Severity Rating from Day 2 to Day 15 (SSR-15). Safety and tolerability of the study drug will be evaluated based on the intensity and course of adverse events (Es).
Enisamium iodide is an antiviral small molecule. Enisamium inhibits replication of alpha- and beta- coronaviruses (human coronavirus NL63 and SARS-CoV-2, respectively) and influenza virus A and B. Mechanism of action against SARS-CoV-2 includes the direct inhibition of the viral RNA polymerase.
详细描述
This randomized, prospective, multi-center, double-blind, placebo-controlled trial, is conducted to investigate the clinical efficacy and safety of the drug Amizon® Max (N-methyl-4-benzylcarbamidopyridinium iodide, international nonproprietary name enisamium iodide, lab code FAV00A) in comparison with placebo, for the treatment of hospitalized patients with RT-PCR confirmed Covid-19 infection.
Enisamium iodide is an antiviral small molecule. Enisamium can directly inhibit influenza viral RNA replication and has antiviral effect against viruses, including coronaviruses (human coronavirus NL63, SARS-CoV-2).Based on the promising in-vitro anti-SARS-CoV-2 activity, it could be assumed that patients suffering from Covid-19 would benefit from a reduced virus load and this could lead to a reduction of Covid-19 typical symptoms that might prevent further complications associated with severe Covid-19 (e.g. active mechanical ventilation).
Adult female and male patients, with Covid-19 infection, will be screened (Day 1) to participate in this trial. If all inclusion/exclusion criteria are fulfilled, randomization to treatment and a start of treatment will occur on Day 1.
Patients will be randomized into 2 treatment groups (1:1) as follows: patients in treatment Group 1 will receive the active treatment with Amizon® Max capsule; patients in treatment Group 2 will receive a placebo capsule. The active treatment and placebo capsules are identical in appearance and size.
Patients will take Amizon® Max capsules 500 mg (active ingredient enisamium iodide) 4 times a day every 6 hours (total daily dose 2,000 mg) for full 7 days. In the control group, patients will take placebo tablets 4 times a day for full 7 days. Patient observation interval is for as long as a subject is hospitalized Day 1 to Day 29. A follow-up visit will be performed on Day 29 (by phone as applicable for all subjects discharged from the hospital before Day 29).
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)
盲法说明
Capsule formulations of the placebo Amizon® Max (IMP-2) is identical in appearance (size, shape, and color), taste, and smell as the active drug capsule.
入排标准
- 年龄范围
- 18 Years 至 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Each subject must meet all of the following inclusion criteria to be randomized to treatment:
- •Willing and able to provide written informed consent
- •Aged ≥ 18 years
- •SARS-CoV-2 infection confirmed by PCR ≤ 4 days before randomization
- •Currently hospitalized due to SARS-CoV-2 infection with fever, defined as body temperature ≥ 37.8 °C
- •Modified World Health Organization (WHO) Ordinal Scale for Clinical Status Patient state in Covid-19: score 4 i.e. hospitalized, virus-positive, oxygen by mask or nasal prongs
排除标准
- •The subject is excluded from the trial if any of the following criteria apply:
- •Concurrent treatment with other agents with actual or possible direct acting antiviral activity against SARS-CoV-2 is prohibited < 24 hours prior to start of IMP treatment
- •Requiring mechanical ventilation at screening or it is expected within 24 h after inclusion
- •Expected survival time < 72 hours for any reason
- •Positive pregnancy test
- •Breastfeeding woman
- •Presence of renal dysfunction defined as estimated glomerular filtration rate (eGFR) <60 mL/min, total bilirubin ≥ 2.0 mg/dL, Thyroid stimulating hormone (TSH) outside normal range and / or Aspartate aminotransferase (ASAT)/ Alanine aminotransferase (ALAT) above threefold upper limit of normal range (known from patients medical history)
- •Known hypersensitivity to the trial drug, the metabolites, or formulation excipient
- •History or presence of drug or alcohol abuse
- •History or presence of diseases of thyroid gland
研究组 & 干预措施
Enisamium iodide
Hospitalized patients who were randomized in to this treatment group will receive enisamium iodide containing capsules (Amizon® Max).
干预措施: Enisamium Iodide (Drug)
Placebo
Hospitalized patients who were randomized in to this treatment group will receive placebo containing capsules.
干预措施: Placebo (Drug)
结局指标
主要结局
Efficacy - Time from day of randomization to an improvement of at least two points (from the status at randomization) on severity rating (SR) scale in days
时间窗: Day 0 to Day 29
Time from day of randomization to an increase of at least two points (from the status at randomization) on the following severity rating (SR) scale in days: 1. - Death 2. - Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) 3. - Hospitalized, on non-invasive ventilation or high flow oxygen devices 4. - Hospitalized, requiring supplemental oxygen 5. - Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (Covid-19 related or otherwise) 6. - Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care 7. - Not hospitalized, limitation on activities and/or requiring home oxygen 8. - Not hospitalized, no limitations on activities
次要结局
- Time to Clinical Recovery (TTCR) of main Covid-19 symptoms/complications or discharge(Day 0 to Day 29)
- Days Alive and Out of Hospital until Day 15 (DAOH-14)(Day 2 to Day 15)
- Proportion of Subjects Discharged by Day 8, 15, 22, 29(Day 0 to Day 29)
- Incidence of non-invasive ventilation(Day 0 to Day 29)
- Days until non-invasive ventilation(Day 0 to Day 29)
- Total days of non-invasive ventilation(Day 0 to Day 29)
- Efficacy - Time to recovery (TTR) from Day 1 (randomization and start of IMP treatment)(Day 0 to Day 29)
- Adverse events (AEs)(Day 0 to Day 29)
- Sum of Severity Rating from Day 2 to Day 15 (SSR-15)(Day 2 to Day 15)
- Severity Rating on Day 15 (SR-15):(Day 15 or Day of discharge (whichever occurs first))
- Incidence of invasive mechanical ventilation or ECMO(Day 0 to Day 29)
- Course of qualitative RT-PCR viral test results(Day 0 to Day 29)
- Overall assessment of efficacy (patient and investigator)(Day 29 or Day of discharge (whichever occurs first))
- Days until invasive mechanical ventilation or ECMO(Day 0 to Day 29)
- Viral test evaluation - Proportion of subjects free of SARS-CoV-2(Days 0, 8, 15, 22, 29)
- Overall assessment of tolerability of treatment (patient and investigator)(Day 29 or Day of discharge (whichever occurs first))