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

A Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety and Efficacy of Intravenous Infusion of CAP-1002 in Patients With COVID-19 (INSPIRE)

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.

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.

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.

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 a 1-point decrease (indicative of improvement) on the WHO Ordinal Scale of Clinical Improvement from start of treatment

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

Absolute values and changes from start of treatment in severity in ARDS as defined by Berlin criteria: 0=none, 2=moderate, 3=severe

Inclusion Criteria: Male or female subjects at least 18 years of age at time of consent. Diagnosis of SARS-CoV-2 infection confirmed by real-time reverse transcription polymerase chain reaction (RT-PCR) assay. 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). 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. Written informed consent provided by subject or legal representative. Exclusion Criteria: Currently receiving extracorporeal membrane oxygenation (ECMO) or high frequency oscillatory ventilation (HFOV). Patients who have been intubated. Patients with established positive bacterial blood cultures prior to enrollment or suspicion of superimposed bacterial pneumonia. Patients with untreated human immunodeficiency virus (HIV) infection. Creatinine clearance less than 30 mL/minute. Liver function tests > 5x normal. Current or history (within the previous 5 years) of systemic autoimmune or connective tissue disease. Known allergy or hypersensitivity to any of the IP constituents such as dimethyl sulfoxide (DMSO) or bovine proteins. Treatment with a cell therapy product within 12 months prior to randomization. Participation in an ongoing protocol studying an experimental drug or device. Pregnant or breastfeeding female subjects, and sexually active female subjects of childbearing potential not willing to use contraceptive methods.