A Phase 1/2 Randomized, Placebo-Controlled Trial of ACT-20 in Patients With Severe COVID-19 Pneumonia
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 70
- 主要终点
- Mortality at day 30
研究概览
简要总结
The primary objective of this study is determine the safety and efficacy of ACT-20-MSC (allogenic human umbilical derived mesenchymal stem cells) and ACT-20-CM (allogenic human umbilical derived mesenchymal stem cells in conditioned media) in patients with moderate to severe COVID-19 pneumonia.
详细描述
This study will assess the safety and efficacy of ACT-20-MSC and ACT-20-CM administered intravenously to subjects with moderate to severe COVID-19 related pneumonia in two parts.
Part 1 is an open-label study of 10 subjects, 5 with moderate COVID-19 pneumonia and 5 with severe COVID-19 pneumonia. Of these 10 subjects, 5 will receive ACT-20-CM and 5 will receive ACT-20-MSC resuspended in ACT-20-CM.
Part 2 is a randomized, blinded, placebo-controlled study of 60 patients, 30 with moderate COVID-19 pneumonia and 30 with severe COVID-19 pneumonia. Randomization will be 1:1:1 ACT-20-MSC in ACT-20-CM, ACT-20-CM or placebo. The placebo is MEM-α, a widely used sterile culture media that contains non-essential amino acids, nucleosides, vitamins, glucose, sodium pyruvate and lipoic acid.
Subjects treated at each investigative site will provide written informed consent prior to the conduct of any study-related procedures. Thereafter, they will be screened and those meeting the inclusion/exclusion criteria will be enrolled into the trial and undergo all the study procedures including the intravenous administration of the investigational medical product (IMP = ACT-20-MSC in ACT-20-CM or ACT-20-CM) or placebo. The IMP will be administered in addition to any standard of care treatment the subject is receiving.
Subjects will be assessed daily while in hospital. Following discharge from hospital, subjects will be following for an additional three month period.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female patients age 18 to 85, inclusive
- •Confirmed positive test for COVID-19 by standard reverse transcriptase polymerase chain reaction (RT-PCR) assay or equivalent
- •On mechanical ventilation (n=35), or high-flow O2 support (n=35) and:
- •Disease severity level of "moderate" (PaO2/FiO2 of 100-200) (n=35), or "severe" (PaO2/FiO2 < 100) (n=35) as established using the Berlin Criteria for ARDS (Barbas, Isola & Caser, 2014; Baron & Levy, 2016).
- •Positive end-expiratory airway pressure (PEEP) ≥ 5 cmH2O
- •Oxygen saturation ≤ 93%
- •Non-cardiogenic bilateral pulmonary edema on frontal chest radiograph that cannot be explained by effusion, collapsed lung or lung nodule
- •Able to understand and provide voluntary informed consent
排除标准
- •Unable to understand and provide voluntary informed consent
- •Current infection with HIV-1, HIV-2, Hepatitis B, Hepatitis C or HTLV
- •History of malignancy, other than non-melanoma skin cancer or non-metastatic prostate cancer
- •Currently receiving extracorporeal life support or high-frequency oscillatory ventilation
- •Weight > 150 kg
- •Current severe chronic respiratory disease, as demonstrated by:
- •PaCO2 > 50 mm Hg, or
- •history of use of home oxygen
- •Major trauma within the past 7 days
- •Lung transplant recipient
- •WHO Class III or IV pulmonary hypertension
- •Documented deep vein thrombosis or pulmonary embolism within the past 3 months
- •Currently pregnant or lactating
- •Currently participating in another clinical trial, or participation in another clinical trial within 30 days of enrollment
- •Hypersensitivity to Dextran-40 or Dimethyl Sulfoxide (DMSO)
- •Current pharmacotherapy using hydroxychloroquine or Interleukin-6 inhibitors
- •History of CVA or MI within 180 days of study enrollment
结局指标
主要结局
Mortality at day 30
时间窗: 30 days post treatment
次要结局
- Ventilated Subjects - Ventilator Free Days(28 days post treatment)
- Both Ventilated and High-Flow O2 Support Subjects - Pulmonary Function Improvement(30 days post treatment, or until off of ventilator or high-flow O2 support)
- Ventilated Subjects - Improvement in Ventilator Settings(28 days post treatment, or until off of ventilator)
- High-Flow O2 Support Subjects - Step-Down O2 Therapy(30 days post treatment, or until off of high-flow O2 support)
- High Flow O2 Support Subjects - Respiration Rate(30 days post treatment, or until off of high-flow O2 support)
- Both Ventilated and High-Flow O2 Support Subjects - ICU-Free Days(30 days post treatment, or until off of ventilator or high-flow O2 support)
- Both Ventilated and High-Flow O2 Support Subjects - Increased Berlin Score(30 days post treatment, or until off of ventilator or high-flow O2 support)