ACT-20 in Patients With Severe COVID-19 Pneumonia

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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A Phase 1/2 Randomized, Placebo-Controlled Trial of ACT-20 in Patients With Severe COVID-19 Pneumonia

Conditions
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COVID-19 Pneumonia

Intervention / Treatment
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* Biological: ACT-20-MSC
* Biological: ACT-20-CM
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ACT-20-MSC in ACT-20-CM<br>Conventional treatment plus ACT-20-MSC in ACT-20-CM administered intravenously | Biological: ACT-20-MSC<br>* 1 million cells / kg body weight in 100 ml in conditioned media<br>|
| Experimental: ACT-20-CM<br>Conventional treatment plus ACT-20-CM administered intravenously | Biological: ACT-20-CM<br>* 100 ml of conditioned media only<br>|
| Placebo Comparator: Placebo<br>Conventional treatment plus placebo (MEM-α) administered intravenously | Biological: Placebo<br>* 100 ml of MEM-α<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality at day 30 |  | 30 days post treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ventilated Subjects - Ventilator Free Days | Number of ventilator-free days | 28 days post treatment | 
| Ventilated Subjects - Improvement in Ventilator Settings | Improvement in ventilator settings: Minute ventilation, PEEP, FiO2 | 28 days post treatment, or until off of ventilator | 
| High-Flow O2 Support Subjects - Step-Down O2 Therapy | Days of step-down O2 therapy as evidenced by: improvement in required volume, change to nasal cannula or face mask delivery or improvement in required concentration. | 30 days post treatment, or until off of high-flow O2 support | 
| High Flow O2 Support Subjects - Respiration Rate | Respiration Rate < 30 for > 24 hours. | 30 days post treatment, or until off of high-flow O2 support | 
| Both Ventilated and High-Flow O2 Support Subjects - ICU-Free Days | Number of 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 - Pulmonary Function Improvement | Improvement in pulmonary function as evidenced by A-A oxygen gradient, O2 saturation | 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 | Increased Berlin Criteria score > 24 hours | 30 days post treatment, or until off of ventilator or high-flow O2 support | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Stem cells, Pneumonia, COVID, COVID-19, Coronavirus, SARS-CoV-2