Intravenous Infusion of CAP-1002 in Patients With COVID-19 (INSPIRE)

• ClinicalTrials.gov Identifier: NCT04623671
• Recruitment Status: Recruiting
• First Posted: November 10, 2020
• Last Update Posted: February 21, 2021
• Sponsor: Capricor Inc.
• Information provided by (Responsible Party): Capricor Inc.

Study Description

Brief Summary:

This is a randomized, double-blind, placebo-controlled study that will enroll subjects with a clinical diagnosis of COVID-19 confirmed by laboratory testing and who are in severe or critical condition as indicated by life-support measures.

Condition or disease	Intervention/treatment	Phase
Covid19	Biological: CAP-1002; Biological: Placebo	Phase 2

Detailed Description:

This is a randomized, double-blind, placebo-controlled study that will enroll subjects with a clinical diagnosis of COVID-19 confirmed by laboratory testing and who are in severe or critical condition as indicated by life-support measures. Prior to protocol procedures, informed consent will be obtained from the subject or a legally authorized representative. Subjects will undergo a screening evaluation to determine eligibility based on the protocol inclusion and exclusion criteria.

The primary objectives of the study are to determine the safety and effectiveness of intravenously infused CAP-1002 in improving clinical outcomes in severely or critically ill patients with COVID-19.

Eligible subjects will be randomized to either the CAP-1002 or placebo group (1:1 ratio) and undergo baseline safety and efficacy assessments approximately 1 to 5 days prior to the administration of investigational product (IP). Treatment administration consists of IP consisting of 150M CDCs or matching placebo on study Day 1. Background standard of care treatment and practices will be maintained for all patients enrolled in the study.

Subjects will complete Screening followed by a Treatment and Follow-up phase. A detailed medical history will be collected, including the presence of any co-morbidities and risk factors believed to be associated with COVID-19 outcomes or emergent factors since the time of infection. Eligibility must be reviewed and confirmed on Day 1 prior to the infusion of IP.

Subjects will be observed during the index hospitalization and monitored for outcome and safety with vital signs (heart rate, blood pressure, respiratory rate, and oxygen saturation), physical examinations, electrocardiograms, clinical laboratory testing including complete blood count and comprehensive metabolic panel, inflammatory markers and adverse events. Blood samples will be collected and submitted to a central laboratory for future proteomic assay assessment. Use of any concomitant medications to treat COVID-19 will be documented.

Follow-up will be conducted on Days 2, 3, 7, 15, 30, 60, and 90 either in the inpatient setting or by telephone if the subject has been discharged. All subject participation will be a maximum of 13 weeks from Screening.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Masking Description: Syringes (60-mL) with amber film-covered barrels
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety and Efficacy of Intravenous Infusion of CAP-1002 in Patients With COVID-19 (INSPIRE)
• Actual Study Start Date: November 15, 2020
• Estimated Primary Completion Date: April 30, 2021
• Estimated Study Completion Date: June 30, 2021

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: CAP-1002; The active pharmaceutical ingredient in CAP-1002 is Cardiosphere-Derived Cells (CDCs). CDCs are known to secrete numerous bioactive elements (growth factors, exosomes) which impact the therapeutic benefits of the cell-based therapy. The mechanism of action is the composite ability to be immunomodulatory, anti-fibrotic and regenerative.	Biological: CAP-1002; 100-mL (total volume) infusion of 150M CDCs in 5% Human Serum Albumin (HSA); Other Names: Cardiosphere-Derived Cells; CDCs
Placebo Comparator: Placebo; Matching placebo solution	Biological: Placebo; Matching placebo solution

Outcome Measures

Primary Outcome Measures :

1. Safety of CAP-1002 [ Time Frame: 90 days ]
   Number of adverse events from start of treatment
2. Efficacy of CAP-1002 on Cytokine [ Time Frame: 30 days ]
   Cytokine absolute values and changes from start of treatment to Day 30.
3. Efficacy of CAP-1002 on Laboratory Biomarker [ Time Frame: 30 days ]
   Biomarker absolute values and changes from start of treatment to Day 30.

Other Outcome Measures:

1. All cause mortality [ Time Frame: 30 days ]
   Number of all cause mortality cases within 30 days from start of treatment
2. ICU Discharge [ Time Frame: 30 days ]
   Number of Intensive Care Unit (ICU) discharges within 30 days from start of treatment
3. Duration in ICU [ Time Frame: 90 days ]
   Duration in ICU from start of treatment (up to 90 days)
4. Hospital Discharge [ Time Frame: 30 days ]
   Number of hospital discharges within 30 days from start of treatment
5. Hospitalization length [ Time Frame: 90 days ]
   Duration in hospital from start of treatment up to Day 90
6. Ventilatory status [ Time Frame: 90 days ]
   Duration of time on supplemental oxygen or mechanical ventilation from start of treatment up to Day 90
7. Acute Respiratory Distress [ Time Frame: 30 days ]
   Severity of ARDS as defined by the Berlin criteria, absolute values and changes from start of treatment to Day 30.
8. Ordinal Scale of Clinical Improvement [ Time Frame: 30 days ]
   Absolute values and changes from start of treatment to Day 30.
9. WHO Ordinal Improvement [ Time Frame: 90 days ]
   Time to a 1-point decrease (indicative of improvement) on the WHO Ordinal Scale of Clinical Improvement from start of treatment
10. Severity vs. Time [ Time Frame: 30 days ]
    Area under the severity versus time curve, where severity is defined by the Ordinal Scale of Clinical Improvement and time is measured from start of treatment to Day 30

Eligibility Criteria

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

Criteria

Inclusion Criteria:

1. Male or female subjects at least 18 years of age at time of consent.
2. Diagnosis of SARS-CoV-2 infection confirmed by real-time reverse transcription polymerase chain reaction (RT-PCR) assay.

3. Compromised respiratory status as defined by the following criteria to maintain arterial oxygen saturation ≥ 92% (where oxygen saturation is assessed by pulse oximetry) OR cardiomyopathy due to COVID-19 (defined as a new drop in ejection fraction to ≤ 50% during COVID-19 with no evidence of obstructive coronary artery disease based on medical records review):

   1. Patients requiring noninvasive positive pressure ventilation.
   2. Patients on nasal canula with flow ≥ 4 L/minute or fraction of inspired oxygen (FiO2) ≥ 36%).
4. Elevation of at least 1 inflammatory marker (IL-1, IL-6, IL-10, TNF-α, ferritin, CRP) defined as ≥ 2x upper limit of laboratory normal reference value.
5. Written informed consent provided by subject or legal representative.

Exclusion Criteria:

1. Currently receiving extracorporeal membrane oxygenation (ECMO) or high frequency oscillatory ventilation (HFOV).
2. Patients who have been intubated.
3. Patients with established positive bacterial blood cultures prior to enrollment or suspicion of superimposed bacterial pneumonia.
4. Patients with untreated human immunodeficiency virus (HIV) infection.
5. Creatinine clearance less than 30 mL/minute.
6. Liver function tests > 5x normal.
7. Current or history (within the previous 5 years) of systemic autoimmune or connective tissue disease.
8. Known allergy or hypersensitivity to any of the IP constituents such as dimethyl sulfoxide (DMSO) or bovine proteins.
9. Treatment with a cell therapy product within 12 months prior to randomization.
10. Participation in an ongoing protocol studying an experimental drug or device.
11. Pregnant or breastfeeding female subjects, and sexually active female subjects of childbearing potential not willing to use contraceptive methods.

Contacts and Locations

Contacts

Contact: Sudhir Borgonha; 3103583200; sborgonha@capricor.com

Contact: Veena Ramanna; 3103583200; vramanna@capricor.com

Locations

United States, California

Cedars-Sinai Medical Center; Recruiting

Los Angeles, California, United States, 90048

Contact: Tracey S Early, BS, MA, CCRP 310-423-1231 tracey.early@cshs.org

Principal Investigator: Oren Friedman, MD

University of California Davis; Recruiting

Sacramento, California, United States, 95817

Contact: Skyler Pearson 916-734-3867 sjpearson@ucdavis.edu

Contact: Erin Hardy 916-734-3866 eehardy@ucdavis.edu

Principal Investigator: Tim Albertson, MD

United States, Michigan

Henry Ford Health System; Recruiting

Detroit, Michigan, United States, 48202

Contact: Katrina Williams, RN 313-399-1539 kwilli35@hfhs.org

Contact: Melissa Resk 3135871639 mresk1@hfhs.org

Principal Investigator: Mayur Ramesh, MD

United States, Texas

PharmaTex Research, LLC; Recruiting

Amarillo, Texas, United States, 79109

Contact: Megan Hazelrigg 806-355-2581 mhazelrigg@ccallp.com

Principal Investigator: David Brabham, MD

Sponsors and Collaborators

Capricor Inc.

Investigators

• Principal Investigator: Tim Albertson, MD; UC Davis

More Information

• Responsible Party: Capricor Inc.
• ClinicalTrials.gov Identifier: NCT04623671
• Other Study ID Numbers: CAP-1002-COVID-19-02
• First Posted: November 10, 2020
• Last Update Posted: February 21, 2021
• Last Verified: February 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

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

Keywords provided by Capricor Inc.:

SARS-CoV-2; COVID; COVID-19; COVID19