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

• ClinicalTrials.gov Identifier: NCT04623671
• Recruitment Status: Completed
• First Posted: November 10, 2020
• Last Update Posted: February 13, 2023
• Sponsor: Capricor Inc.
• Information provided by (Responsible Party): Capricor Inc.

Tracking Information

• First Submitted Date: October 7, 2020
• First Posted Date: November 10, 2020
• Last Update Posted Date: February 13, 2023
• Actual Study Start Date: November 15, 2020
• Actual Primary Completion Date: February 4, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 29, 2022)

Safety of CAP-1002: Incidence of All-Cause Mortality [ Time Frame: 90 days ]

Number of all-cause mortality cases within 90 days from start of treatment

Original Primary Outcome Measures (submitted: November 9, 2020)

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

• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided

Current Other Pre-specified Outcome Measures (submitted: March 29, 2022)

• Change in World Health Organization (WHO) Ordinal Scale of Clinical Improvement [ Time Frame: 30 days ]
  Absolute values and changes from start of treatment to Day 30 on the clinical status of the subject using a 0-8 scale where 0=uninfected (no clinical or virological evidence of infection) to 8=death
• Time to Clinical Improvement on the WHO Ordinal Scale of 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
• Severity versus Time [ Time Frame: 30 days ]
  Area under the severity versus time curve, where severity is defined by the Ordinal Scale of Improvement and time is measured from start of treatment to Day 30
• Time on supplemental oxygen or mechanical ventilation [ Time Frame: 90 days ]
  Days on supplemental oxygen or ventilation since start of treatment
• Number of Intensive Care Unit (ICU) Discharges [ Time Frame: 30 days ]
  First ICU discharge within 30 days from start of treatment
• Number of Days in ICU [ Time Frame: 90 days ]
  Duration in ICU from start of treatment (up to 90 days)
• Number of Hospital Discharges [ Time Frame: 30 days ]
  Number of hospital discharges within 30 days from start of treatment
• Number of Days in Hospital [ Time Frame: 90 days ]
  Hospitalization length from start of treatment up to Day 90
• Changes in severity of Acute Respiratory Distress Syndrome (ARDS) by Berlin Criteria [ Time Frame: 30 days ]
  Absolute values and changes from start of treatment in severity in ARDS as defined by Berlin criteria: 0=none, 2=moderate, 3=severe
• Change in levels of cytokines: IL-1, IL-6, TNF-alpha, INF-gamma, IL-10 [ Time Frame: 30 days ]
  Cytokine assay absolute values and changes from start of treatment to Day 30
• Changes in levels of biomarkers: C-Reactive Protein, troponin I, myoglobin, ferritin, procalcitonin [ Time Frame: 30 days ]
  Biomarker assay absolute values and changes from start of treatment to Day 30

Original Other Pre-specified Outcome Measures (submitted: November 9, 2020)

• All cause mortality [ Time Frame: 30 days ]
  Number of all cause mortality cases within 30 days from start of treatment
• ICU Discharge [ Time Frame: 30 days ]
  Number of Intensive Care Unit (ICU) discharges within 30 days from start of treatment
• Duration in ICU [ Time Frame: 90 days ]
  Duration in ICU from start of treatment (up to 90 days)
• Hospital Discharge [ Time Frame: 30 days ]
  Number of hospital discharges within 30 days from start of treatment
• Hospitalization length [ Time Frame: 90 days ]
  Duration in hospital from start of treatment up to Day 90
• Ventilatory status [ Time Frame: 90 days ]
  Duration of time on supplemental oxygen or mechanical ventilation from start of treatment up to Day 90
• 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.
• Ordinal Scale of Clinical Improvement [ Time Frame: 30 days ]
  Absolute values and changes from start of treatment to Day 30.
• 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
• 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

Descriptive Information

• Brief Title: Intravenous Infusion of CAP-1002 in Patients With COVID-19
• 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)
• Brief Summary: This is a randomized, double-blind, placebo-controlled, Pilot, Phase 2 Exploratory 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.

Detailed Description

This is a randomized, double-blind, placebo-controlled Pilot, Phase 2 Exploratory 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 Type: Interventional
• Study Phase: Phase 2

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Masking Description:

Syringes (60-mL) with amber film-covered barrels

Primary Purpose: Treatment

• Condition: Covid19

Intervention

• Biological: CAP-1002
  100-mL (total volume) infusion of 150M CDCs in 5% Human Serum Albumin (HSA)
  Other Names:

  • Cardiosphere-Derived Cells
  • CDCs
• Biological: Placebo
  Matching placebo solution

Study Arms

• 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.
  Intervention: Biological: CAP-1002
• Placebo Comparator: Placebo
  Matching placebo solution
  Intervention: Biological: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 4, 2022): 63
• Original Estimated Enrollment (submitted: November 9, 2020): 60
• Actual Study Completion Date: February 4, 2022
• Actual Primary Completion Date: February 4, 2022 (Final data collection date for primary outcome measure)

Eligibility 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 arterial oxygen saturation < 92% (oxygen saturation measured 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).
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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04623671
• Other Study ID Numbers: CAP-1002-COVID-19-02
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Capricor Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Capricor Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Tim Albertson, MD; UC Davis

• PRS Account: Capricor Inc.
• Verification Date: March 2022