A Phase III, Randomized, Placebo-controlled, Clinical Trial to Evaluate the Efficacy and Safety of Co-administered Niclosamide in Patients Treated With an Established Regimen for Novel Coronavirus Infectious Disease (COVID-19)
试验速览
- 阶段
- 3 期
- 发起方
- 入组人数
- 200
- 试验地点
- 8
- 主要终点
- Physician's judgment on clinical recovery from the time of admission
研究概览
简要总结
This study aims to investigate the potential antiviral efficacy and safety of a novel formulation of Niclosamide; a well-known antihelmintic agent, together with an established COVID-19 treatment regimen in patients.
The aim of this study is to evaluate the safety and efficacy profile of niclosamide from the test product (Niclosamide 200 mg/10 mL Suspension) in patients treated for the novel coronavirus infectious disease (COVID-19) in a placebo controlled phase III trial. Both treatment groups will receive an established treatment regimen against COVID-19 together with either niclosamide or placebo.
The efficacy and safety of the molecule is well-known and the properties of novel formulation is well-established. The promising in vitro results of niclosamide as an antiviral compound is well documented and make it an ideal candidate as a therapy against SARS-CoV 2 infection. A good safety profile is expected with solid antiviral activity.
详细描述
The study will be performed in accordance with the relevant articles of the Declaration of Helsinki (1964) as revised in Tokyo (1975), Venice (1983), Hong Kong (1989), Somerset West, RSA (1996), Edinburgh (2000), Washington (2002), Tokyo (2004) and Seoul (2008) and Fortaleza (2013).
The medications for the established treatment regimen will be supplied by Ministry of Health to the study sites. The other study medications, Investigational product and placebo, together with relative documentation, will be supplied to clinical sites by the sponsor. Niclosamide 200 mg/10 mL Suspension and placebo will be supplied together with certificates of analysis by the company responsible for manufacturing of the test product(s).The packaging and labelling of niclosamide and placebo will be done according to the GMP and GCP requirements.
All subjects will receive either 200 mg/10 mL niclosamide suspension or 10 mL placebo three times a day for 5 days, together with an established COVID-19 treatment regimen according to the official guidance for COVID-19 Adult Treatment Algorithm of Republic of Turkey Ministry of Health. Dosings will be administered in accordance with the treatment randomization table throughout the treatment duration.
On each drug administration, the identity of the subject will be confirmed by checking the Identity Card. Administration of the study medication will be performed by the investigator(s) and nurse(s) and supervised by a second medical professional to ensure the correctness of drug administration. Also, a monitor may attend during this procedure. The administration of the study medication is to be followed by a mouth check, to be documented in the CRF and certified by the Investigator.
The statistical analysis will be done according to the provisions of ICH Topic E9, Statistical Principles for Clinical Trials (CPMP/ICH/363/96), September 1998.
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
- Triple (Participant, Care Provider, Investigator)
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
- •Being able to understand the study and to give a written informed consent
- •Adult hospitalized patients (aged ≥18) confirmed or suspected for COVID-19 according to the official General Information, Epidemiology and Diagnosis Guidance for COVID-19 (SARS-CoV-2 Infection) published by Republic of Turkey Ministry of Health showing at least one of the symptoms below:
- •fever, cough, difficulty in breathing, sore throat, headache, muscle or body aches, new loss of taste or smell, diarreha without explanation of any cause than COVID-19 and history of herself/himself or her/his close contact presenting in the high-risk area of the disease within 14 days prior to the onset of symptoms or
- •at least one of the symptoms of fever, cough, difficulty in breathing, sore throat, headache, muscle or body aches, new loss of taste or smell, diarrhea without explanation of any cause than COVID-19 and close contact with confirmed COVID-19 case within 14 days prior to symptoms or
- •fever and at least one of the signs and symptoms of the severe acute respiratory infection (cough and difficulty in breathing) and need for hospitalization due to severe acute respiratory infection (SARI) explanation failure of the clinical features other than COVID-19 SARI: The need for hospitalization in a patient with acute respiratory infection due to fever, cough and dyspnea, tachypnea, hypoxemia, hypotension, wide radiological findings and consciousness developing in the last 14 days.
- •at least two of the signs and symptoms of fever, cough, difficulty in breathing, sore throat, headache, muscle or body aches, new loss of taste or smell, diarrhoea without explanation of any cause than COVID-19 or
- •Patients detected with SARS-COV-2 by molecular methods who meet the criteria for possible case of SARS-COV-2
排除标准
- •Who have allergy to niclosamide and/or any of the treatment agents and/or any of the excipients of the products,
- •Who is diagnosed as "severe or critical case" (e.g. pneumonia or severe pneumonia),
- •Whose National Early Warning Score 2 (NEWS2) score is indicated as "urgent" or "emergency",
- •Any history of bone marrow transplant, solid-organ transplant, immune compromising conditions, immunomodulatory therapy, haematologic malignancy,
- •Who have Multiple Sclerosis,
- •Who have electrolyte imbalance, chronic haemodialysis or glomerular filtration rate < 30 30 mL/min/1.73m2,
- •Who have history of serious cardiovascular diseases,
- •Who are diagnosed with another ongoing viral infection other than SARS CoV-2,
- •Who have macrophage activation syndrome,
- •Who have a need for coagulopathy treatment,
- •Who have severe liver disease,
- •Who is pregnant or nursing,
- •Who are not suitable to 1st articles of inclusion criteria,
- •Who is not eligible to swallow oral medications,
- •Who use vitamin C as supplementary medication during the study,
- •Who are included in another trial.
研究组 & 干预措施
Intervention Arm-I
Niclosamide 200 mg/10 mL Suspension will be administered to patients 3 times a day for 5 days along with the treatment regimen selected according to the official guidance for COVID-19 Adult Treatment Algorithm established by Republic of Turkey Ministry of Health
干预措施: Niclosamide suspension (Drug)
Intervention Arm-II
10 mL placebo will be administered to patients 3 times a day for 5 days along with the treatment regimen selected according to the official guidance for COVID-19 Adult Treatment Algorithm established by Republic of Turkey Ministry of Health
干预措施: Placebo (Other)
结局指标
主要结局
Physician's judgment on clinical recovery from the time of admission
时间窗: Day 1 to day 19
The physician will check for the following symptoms: * Fever: axillary temperature ≤36.6°C or oral temperature ≤37.2 °C; * Respiratory rate: ≤24/minute on room air; * Oxygen saturation: \>94% on room air; * Cough: mild or absent on a patient reported scale of severe, moderate, mild, absent.)
次要结局
- Improvement in serum biomarkers(Day 1 to day 3)
- Requirement for indotracheal intubation(Day 1 to day 19)
- Occurrence of Macrophage Activation Syndrome(MAS)(Day 1 to day 19)
- Clinical improvement in NEWS2(3 days from admission)
- Occurrence of Coagulopathy(Day 1 to day 19)