ACT-20 in Patients With Severe COVID-19 Pneumonia

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

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.

Study Overview

• Status: Unknown
• Conditions: COVID-19 Pneumonia
• Intervention / Treatment: Biological: ACT-20-MSC; Biological: ACT-20-CM; Biological: Placebo

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 Type: Interventional
• Enrollment (Anticipated): 70
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Laura Fairbairn; Phone Number: 403-921-5854; Email: regulatory@aspire2cure.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Aspire Health Science

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Anticipated): May 1, 2020
• Primary Completion (Anticipated): October 1, 2020
• Study Completion (Anticipated): October 1, 2020

Study Registration Dates

• First Submitted: May 20, 2020
• First Submitted That Met QC Criteria: May 20, 2020
• First Posted (Actual): May 21, 2020

Study Record Updates

• Last Update Posted (Actual): May 21, 2020
• Last Update Submitted That Met QC Criteria: May 20, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: SARS-CoV-2; Stem cells; Pneumonia; Coronavirus; COVID-19; COVID
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Lung Diseases; COVID-19; Pneumonia
• Other Study ID Numbers: AHS 20-03

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No