ACT-20 in Patients With Severe COVID-19 Pneumonia

Phase 1

• Conditions: COVID-19 Pneumonia
• Interventions: Biological: ACT-20-CM; Biological: Placebo; Biological: ACT-20-MSC

• Registration Number: NCT04398303
• Lead Sponsor: Aspire Health Science

Brief Summary

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

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.

Study Timeline

• Status Verified: 2020-05
• Study Start: 2020-05
• Study First Submitted: 2020-05-20
• Study First Submitted QC: 2020-05-20
• Last Update Submitted: 2020-05-20
• Study First Posted: 2020-05-21
• Last Update Posted: 2020-05-21
• Primary Completion: 2020-10
• Study Completion: 2020-10

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 70

Inclusion Criteria

1. Male or female patients age 18 to 85, inclusive

2. Confirmed positive test for COVID-19 by standard reverse transcriptase polymerase chain reaction (RT-PCR) assay or equivalent

3. On mechanical ventilation (n=35), or high-flow O2 support (n=35) and:

   1. 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).
   2. Positive end-expiratory airway pressure (PEEP) ≥ 5 cmH2O
   3. Oxygen saturation ≤ 93%

4. Non-cardiogenic bilateral pulmonary edema on frontal chest radiograph that cannot be explained by effusion, collapsed lung or lung nodule

5. Able to understand and provide voluntary informed consent

Exclusion Criteria

1. Unable to understand and provide voluntary informed consent

2. Current infection with HIV-1, HIV-2, Hepatitis B, Hepatitis C or HTLV

3. History of malignancy, other than non-melanoma skin cancer or non-metastatic prostate cancer

4. Currently receiving extracorporeal life support or high-frequency oscillatory ventilation

5. Weight > 150 kg

6. Current severe chronic respiratory disease, as demonstrated by:

   1. PaCO2 > 50 mm Hg, or
   2. history of use of home oxygen

7. Major trauma within the past 7 days

8. Lung transplant recipient

9. WHO Class III or IV pulmonary hypertension

10. Documented deep vein thrombosis or pulmonary embolism within the past 3 months

11. Currently pregnant or lactating

12. Currently participating in another clinical trial, or participation in another clinical trial within 30 days of enrollment

13. Hypersensitivity to Dextran-40 or Dimethyl Sulfoxide (DMSO)

14. Current pharmacotherapy using hydroxychloroquine or Interleukin-6 inhibitors

15. History of CVA or MI within 180 days of study enrollment

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ACT-20-CM	ACT-20-CM	Conventional treatment plus ACT-20-CM administered intravenously
Placebo	Placebo	Conventional treatment plus placebo (MEM-α) administered intravenously
ACT-20-MSC in ACT-20-CM	ACT-20-MSC	Conventional treatment plus ACT-20-MSC in ACT-20-CM administered intravenously

Primary Outcome Measures

Name	Time	Method
Mortality at day 30	30 days post treatment

Secondary Outcome Measures

Name	Time	Method
Ventilated Subjects - Ventilator Free Days	28 days post treatment	Number of ventilator-free days
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	Improvement in pulmonary function as evidenced by A-A oxygen gradient, O2 saturation
Ventilated Subjects - Improvement in Ventilator Settings	28 days post treatment, or until off of ventilator	Improvement in ventilator settings: Minute ventilation, PEEP, FiO2
High-Flow O2 Support Subjects - Step-Down O2 Therapy	30 days post treatment, or until off of high-flow O2 support	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.
High Flow O2 Support Subjects - Respiration Rate	30 days post treatment, or until off of high-flow O2 support	Respiration Rate \< 30 for \> 24 hours.
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	Number of ICU-free days
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	Increased Berlin Criteria score \> 24 hours