ALlogeneic Cardiosphere-derived Stem Cells (CDCs) for Pulmonary Hypertension therApy

NCT03145298 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: IND 16686
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

Pulmonary Arterial Hypertension or PAH is a progressive condition for which there is no cure. Even with substantial pharmacologic advances in the modern treatment era, survival still remains unacceptably poor, as reported in large PAH registries. Preclinical studies suggest that the administration of allogeneic CDCs have the potential to reduce adverse arteriolar remodeling in PAH which was the basis for the approved investigational new drug (IND). The use of CDCs as an adjunctive therapy in patients comprising 4 sub-groups of patients with PAH in which inflammation and immune dysfunction are key pathophysiologic drivers of PAH.

Conditions

Pulmonary Arterial Hypertension (PAH)

Keywords

HPAH (heritable); IPAH (idiopathic); PAH-CTD (connective tissue diseases); PAH-HIV (human immunodeficiency virus)

Outcome Measures

Primary Outcomes (1)

• Primary Safety (Early) endpoints including the determination of Gas Exchange and Hemodynamics; Detection of Arrhythmias; Sudden unexpected death and Mortality and Morbidity

  * Determination of Gas Exchange: Significant hypoxemia within the 1st 72 hours following the infusion of CAP-1002 cells as determined by arterial blood gas analysis or pulse oximetry on or off O2, which is a distinct change from values obtained at screening. (PaO2 \< 55mmHg; SPO2 \< 85%). * Determination of Hemodynamics: Significant tachycardia and hypotension; while PA cath in-situ: fall in cardiac output; significant rise in PA systolic pressure, mean right atrial pressure. Note, hemodynamic measurements will be obtained, as clinically indicated over a 1-hour time frame post CDC infusion. If the patient is deemed stable after this 1-hour time frame, the PA catheter will be withdrawn in the cardiac catheterization laboratory, and the patient will be transferred to the ICU for further monitoring. * Detection of Arrhythmias: development of supra-ventricular tachyarrhythmias

  Within 72 hours of infusion

Secondary Outcomes (2)

• Secondary Safety (Long Term) endpoints including ongoing monitoring of events listed for primary safety endpoints as well as long term monitoring for a composite of time to clinical worsening.

  One year

• Exploratory Secondary Efficacy Endpoints measuring right ventricular function and pressure estimates

  One year

Study Arms (2)

Biological: Allogeneic Human Cardiosphere-Derived Cells (CDCs)

EXPERIMENTAL

The Phase 1a portion (N=6 subjects) consists of an open-label, single-arm, study design - dose escalation. The potentially conducted Phase 1b portion of the study (N=20 subjects) consists of a double-blind, randomized, placebo-controlled study design.

Biological: Allogeneic Human Cardiosphere-Derived Stem Cells

Placebo

PLACEBO COMPARATOR

The placebo study arm only applies to the Phase Ib portion of the study design. The Phase Ia portion (N=6 subjects) consists of an open-label, single-arm, study design. The potentially conducted Phase Ib portion of the study (N=20 subjects) consists of a double-blind, randomized, placebo-controlled study design with a 1:1 ratio.

Biological: Placebo

Interventions

Allogeneic Human Cardiosphere-Derived Stem Cells BIOLOGICAL

Human Allogeneic Cardiosphere-Derived Cells is a biologic product consisting largely of cells grown from donated human heart muscle tissue

Also known as: CAP-1002

Biological: Allogeneic Human Cardiosphere-Derived Cells (CDCs)

Placebo BIOLOGICAL

For use in Phase 1b - Double-blind randomized control portion of the study

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Confirmed clinical diagnosis of IPAH, HPAH, PAH-CTD, PAH-HIV
• NYHA Functional Class: II or III
• MWD \> 150 m
• Able to maintain O2 saturation at rest ≥ 90% (with or without supplemental O2). O2 use during the course of the study is permitted.
• The subjects must be on PAH-specific therapies for at least 4 months and on a stable dose for at least 4 weeks prior to enrollment into study. PAH-specific agents can include: prostanoids, prostacyclin receptor agonist, endothelin receptor antagonists, phosphodiesterase-5 inhibitors and soluble guanylate cyclase stimulator agents alone or in combination
• All patients with PAH-HIV must be on a stable and effective HAART combination regimen
• Pulmonary capillary wedge pressure (PCWP) or LVEDP \< 15 mm Hg
• Age: 18 -75 years
• Ability to provide informed consent and follow-up with protocol procedures

You may not qualify if:

• Diagnosis of PAH other than IPAH, HPAH, PAH-CTD or PAH-HIV
• Right atrial pressure \> 20 mmHg as measured by right heart catheterization (RHC) on day of pre-infusion
• History of clinically-significant coronary artery disease, including myocardial infarction, coronary stent placement or coronary artery bypass surgery within the previous 5 years, LV dysfunction
• History or demonstration of significant ventricular tachy-arrhythmias or conduction abnormalities
• Significant interstitial lung disease (on imaging and PFTs; FVC: \< 60%;
• Chronic thromboembolic pulmonary hypertension (CTEPH)
• Estimated glomerular filtration rate (GFR) ≤ 50 mL/min
• Active uncontrolled infection
• Non-pulmonary vascular disease with life expectancy of \< 3 years
• Hypersensitivity to contrast agents
• Active allergic reactions
• History of previous stem cell therapy
• Participation in an on-going protocol studying an experimental drug or device
• Current alcohol or drug abuse because of anticipated difficulty in complying with protocol-related procedures
• Pregnant/nursing women as well as men and women of child-bearing potential without use of active and highly reliable contraception

Sponsors & Collaborators

• Cedars-Sinai Medical Center: lead
• California Institute for Regenerative Medicine (CIRM): collaborator

Study Sites (1)

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

MeSH Terms

Conditions

Pulmonary Arterial Hypertension; Connective Tissue Diseases; Acquired Immunodeficiency Syndrome

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases; Skin and Connective Tissue Diseases; HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Officials

• Michael I Lewis, MD

  Cedars-Sinai Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Notification of subject randomization will be received by an independent storage/distribution center; the storage/distribution center will have password protected access to the randomization in order to retrieve the treatment assignment. The storage/distribution center will randomly assign an appropriate donor (or placebo) once they receive the designation of active treatment vs. placebo from the interactive system. All Sponsor staff will remain blinded to treatment (CAP-1002 or placebo) assignments. The only time other Sponsor staff will become aware of individual treatments is in the case of an emergency blind break resulting from an SAE.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Cedars-Sinai Heart Institute

Model Details: The study is divided into two portions. The first (Phase 1a) evaluates safety and efficacy of 2 different doses of cells (50 and 100 million cells). The second phase (Phase 1b) takes place after an independent data safety monitoring board has reviewed all the data from Phase 1a and deems it safe and appropriate to proceed to Phase 1b. The latter is a randomized double-blind study in which subjects receive either CAP-1002 or placebo in a 1:1 ratio.

Study Record Dates

• First Submitted: May 2, 2017
• First Posted: May 9, 2017
• Study Start: October 1, 2017
• Primary Completion: January 31, 2023
• Study Completion: March 31, 2023
• Last Updated: June 12, 2023

Record last verified: 2023-06

Locations

US (1)