A prospective, randomized, comparative, multi-centric, adaptive design clinicalstudy to evaluate efficacy, safety and tolerability of 101-PGC-005 (‘005) for the treatment of moderate COrona VIrus Disease (Covid-19) disease patients.
试验速览
- 阶段
- 2/3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 62
- 试验地点
- 7
- 主要终点
- Clinical improvement or shift in WHO 11-point ordinal scale rating.
研究概览
简要总结
Coronavirus disease 2019 (COVID-19) is defined as illness caused by a novel coronavirus now called Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2; formerly called 2019-nCoV), which was first identified amid an outbreak of respiratory illnesscases in Wuhan City, Hubei Province, China. It was initially reported to the WHO on December 31, 2019. On January 30, 2020, the WHO declared the COVID-19 outbreak a global health emergency.
COVID-19 disease does not have any approved treatment. However, an array of drugs approved for other indications, as well as multiple investigational agents, are being studied for the treatment of COVID-19 in several hundred clinical trials around the globe. The recent RECOVERY Trial demonstrated the success of dexamethasone in treating late stage COVID-19 patients. However, use ofDexamethasone increased mortality in early stage of the disease and due to limitations of use of free dexamethasone because of the dose and duration that is insufficient to properly treat COVID-19 patients. As majority of the cells have glucocorticoid receptors to which the dexamethasone binds, highly toxic dose would be needed to effectively treat . COVID-19 disease which would result in increase in mortality and this dose may modulate T cells and other immune cells, resulting in decreased natural immunity. 101-PGC-005 (‘005), which is a prodrug of dexamethasone will address the many safety issues limiting this most powerful anti-inflammatory agent.
This is a prospective, randomized, comparative, multi-centric, adaptive design clinical study to evaluate efficacy, safety and tolerability of 101-PGC-005 (‘005) when used alongside Standard of Care (SOC) for the treatment of hospitalized patients with coronavirus disease (COVID-19).
研究设计
- 研究类型
- Interventional
- 分配方式
- Computer generated randomization
- 盲法
- Open Label
入排标准
- 年龄范围
- 18.00 Year(s) 至 65.00 Year(s)（—）
- 性别
- All
入选标准
- •1.Patients willing and able to provide voluntary written informed consent and to follow the protocol specific requirements.
- •Male or female patients of age 18 to 65 years (both inclusive).
- •Patients with ‘moderate’ COVID-19 disease severity, as defined by Comprehensive Guidelines for Management of COVID-19 patients, Directorate General of Health Services, MoHFW, GOI; AND having any of the following symptoms and signs prior to randomization: a.
- •Fever, cough, with or without sore throat/throat irritation, body ache/headache, malaise/weakness, diarrhoea or gastrointestinal upset, with or without anorexia/nausea/vomiting, with or without loss of smell and/or taste, shortness of breath/breathlessness and difficulty in breathing b.
- •Respiratory rate of >24 to <30 breaths/min, c.
- •SpO2: 90 – 93% on room air
- •Patients with positive RT-PCR test for SARS-CoV-2 in nasopharyngeal or oropharyngeal swabs (sample collected within 7 days prior to randomization)
- •Elevated CRP, ESR or Ferritin levels
- •In case of female patients of child-bearing potential, a negative urine pregnancy test prior to beginning the therapy.
- •Willing to sign voluntary informed consent for participation in the study and willing to adhere to all protocol procedures.
- •In case the subject is unable to provide informed consent than the same should be obtained from legally acceptable representative (LAR).
排除标准
- •Patients with ‘mild’ or ‘severe’ COVID-19 disease severity, as defined by latest Comprehensive Guidelines for Management of COVID-19 patients, Directorate General of Health Services, MoHFW, GOI at the time of randomization.
- •This includes any one or more of the following a.
- •Peripheral Blood oxygen saturation ≥94% or <90% b.
- •Respiratory Rate or <24 or ≥30 breaths per minute
- •First positive RT-PCR more than 7 days prior to treatment administration
- •Patients with evidence of other serious infectious, malignant, autoimmune, kidney, hepatic, cardiovascular or other systemic disease and/or laboratory abnormality, which, in the opinion of the investigator, prevent the patient from participating in the study
- •Subjects with Chronic liver disease (Child Pugh class B or C) and chronic renal disease (GFR<30ml/min).
- •Renal dysfunction [Serum Creatinine > 2.5 times of ULN or calculated creatinine clearance < 30ml/min], Liver Dysfunction [Total Bilirubin > 3times ULN & AST/ALT > 5times ULN].
- •Chronic systemic glucocorticoid treatment or any immunosuppressive treatment
- •History of human immunodeficiency virus (HIV) or active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV)
- •Pregnant and Lactating patients.
- •Patients who require IL-6 inhibitors for management of inflammation at the time of study entry.
- •Subject has a psychiatric disease that is not well controlled where controlled is defined as: stable on a regimen for more than one year.
- •Hospital discharge is anticipated in ≤ 24 hours or anticipated transfer to another hospital which is not a study site within 72 hours.
- •Patients that are currently or have participated in such studies participating in other clinical studies with investigational drug, biological agent or device within 1 month or within 5 half-lives (of the drug/biologic) prior to randomization (whichever is longer).
结局指标
主要结局
Clinical improvement or shift in WHO 11-point ordinal scale rating.
时间窗: Time-points: Baseline through Day 10, Day 14 and Day 28
次要结局
- Time to respiratory viral clearance(Time points: 3, 7, 10, 14 Days)
- Improvement in COVID-19 Symptoms such as Fever, Heart Rate and Oxygen(Saturation)
- Improvement biochemical inflammatory markers such as CRP,Neutrophil-Lymphocyte(N/L) ratio, D-Dimer, Sr. Ferritin, IL-6, TNF-α(Time points: Baseline, Day 14, Day 28)
- Requirement of auxiliary oxygen therapy(Time frame: 28 Days)
- Discharge Rate from hospital(Time frame: 28 Days)
- Improvement in lung injury on Chest HRCT(Time frame: Baseline, 14, 28 days)
- Rate of ICU Admission / Mechanical Ventilation(Time frame: 28 Days)
- All-cause mortality
- Changes in Lab. Safety Values for CBC, LFT, KFT, FPG(Changes in Lab. Safety Values for CBC, LFT, KFT, FPG)
- Adverse events (serious/Non-serious, Expected/Unexpected, Related/Non-Related)(Time frame: 21 days)
- Vital Signs, Physical Examination & other safety evaluation (ECG) analysis(Time frame: 28 days)