ACT-20 in Patients With Severe COVID-19 Pneumonia

• ClinicalTrials.gov Identifier: NCT04398303
• Recruitment Status: Unknown
• First Posted: May 21, 2020
• Last Update Posted: May 21, 2020
• Sponsor: Aspire Health Science
• Information provided by (Responsible Party): Aspire Health Science

Study Description

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.

Condition or disease	Intervention/treatment	Phase
COVID-19 Pneumonia	Biological: ACT-20-MSC; Biological: ACT-20-CM; Biological: Placebo	Phase 1; Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 70 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase 1/2 Randomized, Placebo-Controlled Trial of ACT-20 in Patients With Severe COVID-19 Pneumonia
• Estimated Study Start Date: May 2020
• Estimated Primary Completion Date: October 2020
• Estimated Study Completion Date: October 2020

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Mortality at day 30 [ Time Frame: 30 days post treatment ]

Secondary Outcome Measures :

1. Ventilated Subjects - Ventilator Free Days [ Time Frame: 28 days post treatment ]
   Number of ventilator-free days
2. Ventilated Subjects - Improvement in Ventilator Settings [ Time Frame: 28 days post treatment, or until off of ventilator ]
   Improvement in ventilator settings: Minute ventilation, PEEP, FiO2
3. High-Flow O2 Support Subjects - Step-Down O2 Therapy [ Time Frame: 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.
4. High Flow O2 Support Subjects - Respiration Rate [ Time Frame: 30 days post treatment, or until off of high-flow O2 support ]
   Respiration Rate < 30 for > 24 hours.
5. Both Ventilated and High-Flow O2 Support Subjects - ICU-Free Days [ Time Frame: 30 days post treatment, or until off of ventilator or high-flow O2 support ]
   Number of ICU-free days
6. Both Ventilated and High-Flow O2 Support Subjects - Pulmonary Function Improvement [ Time Frame: 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
7. Both Ventilated and High-Flow O2 Support Subjects - Increased Berlin Score [ Time Frame: 30 days post treatment, or until off of ventilator or high-flow O2 support ]
   Increased Berlin Criteria score > 24 hours

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Contacts

Contact: Laura Fairbairn; 403-921-5854; regulatory@aspire2cure.com

Sponsors and Collaborators

Aspire Health Science

More Information

Additional Information:

Related Info 

• Responsible Party: Aspire Health Science
• ClinicalTrials.gov Identifier: NCT04398303
• Other Study ID Numbers: AHS 20-03
• First Posted: May 21, 2020
• Last Update Posted: May 21, 2020
• Last Verified: May 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Aspire Health Science:

Stem cells; Pneumonia; COVID; COVID-19; Coronavirus; SARS-CoV-2

Additional relevant MeSH terms:

COVID-19; Pneumonia; Pneumonia, Viral; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases