Dilated cardiomYopathy iNtervention With Allogeneic MyocardIally-regenerative Cells (DYNAMIC)

Capricor Therapeutics

Status and phase: Unknown; Phase 1

Conditions: Dilated Cardiomyopathy (DCM); Heart Failure; Nonischemic Cardiomyopathy; Ischemic Cardiomyopathy

Treatments: Biological: Allogeneic Cardiosphere-Derived Cells (CDCs)

Study type: Interventional

Funder types: Other; Industry; NIH

Identifiers

NCT02293603

CAP-1002 (DYNAMIC)

R44HL095203 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

To determine the safety profile of CAP-1002 administered by multi-vessel intracoronary infusion in subjects with DCM. The study will further explore safety and exploratory efficacy endpoints of CAP-1002.

Full description

Eligible subjects will undergo sequential intracoronary infusion of CAP-1002 or placebo in up to three coronary arteries supplying three major cardiac territories to the heart (anterior, lateral, inferior/posterior). After completion of the screening procedures, Phase Ia subjects will receive CAP-1002 administered via intracoronary infusion in a dose escalation, stepwise manner. Phase Ia subjects will be followed at Week 2 and at Months 1, 2, 3, 6 and 12 after CAP-1002 infusion. The first fourteen (14) subjects will receive intracoronary infusion of CAP-1002 in an open-label fashion (Phase Ia). Once all 14 subjects in the Phase Ia have reached the primary safety endpoint (1 month visit), the DSMB will conduct a review of the Phase Ia data and recommend whether to proceed with enrollment of the next 28 subjects in the Phase Ib.

Enrollment: 42 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Major Inclusion Criteria:

1. DCM with left ventricular ejection fraction (LVEF) ≤ 35% as determined by a historical TTE within the previous 6 months
2. New York Heart Association (NYHA) Class III or ambulatory Class IV heart failure
3. Use of evidence based medical-therapy (beta-blockers, ACE-inhibitors/angiotensin receptor blockers, aldosterone antagonist) and with or without device-therapy (Implantable cardioverter-defibrillator or cardiac resynchronizing therapy), in accordance with the ACC/AHA guidelines for the management of heart failure, for at least three months prior to enrollment or documented contraindication or intolerance or patient preference
4. Coronary anatomy suitable for Investigational Product (IP) infusion, as determined by the Eligibility Committee (a team of cardiology experts)
5. Ability to provide informed consent and follow-up with protocol procedures
6. Screening cardiac CT left ventriculogram ejection fraction <40% with left ventricular dilatation
7. Age ≥ 18 years

Major Exclusion Criteria:

1. Diagnosis of active myocarditis
2. Immunologic incompatibility with all available Master Cell Banks (MCBs) by single-antigen bead (SAB) serum antibody profiling
3. Left Ventricular Assist Devices (LVAD) or those actively in the process of acquiring one
4. Recent placement of a cardiac pacemaker and/or resynchronization pacing therapy within the past three months or those actively in the process of acquiring one
5. History of sustained ventricular tachycardia (VT) requiring cardiopulmonary resuscitation (with the exception of subjects who subsequently received an ICD)
6. Non-cardiovascular disease with life expectancy of < 3 years
7. Known hypersensitivity to contrast agents
8. Estimated glomerular filtration rate (GFR) < 50 mL/min
9. Active infection not responsive to treatment
10. Active allergic reactions, connective tissue disease or autoimmune disorders
11. History of cardiac tumor, or cardiac tumor demonstrated on screening
12. History of previous stem cell therapy
13. History of treatment with immunosuppressive agents, including chronic systemic corticosteroids, biologic agents targeting the immune system, anti-tumor and anti-neoplastic drugs or anti-vascular endothelial growth factor (VEGF) within 6 months prior to enrollment (not including drug eluting coronary stents)
14. History of receipt of chemotherapeutic agents known to be implicated in cardiac dysfunction [Adriamycin, trastuzumab (Herceptin)]
15. Known moderate-severe aortic stenosis/insufficiency or severe mitral stenosis/regurgitation
16. Participation in an on-going protocol studying an experimental drug or device
17. Current active alcohol or drug abuse or inability to comply with protocol-related procedures
18. Pregnant/nursing women and women of child-bearing potential without use of active and highly reliable contraception
19. Known history of Human Immunodeficiency Virus (HIV) infection
20. Known history of chronic viral hepatitis
21. Abnormal liver function (serum glutamic pyruvic transaminase (SGPT) > 10 times the upper reference range) and/or abnormal hematology (hematocrit < 25%, white blood cells (WBC) < 3000 µl, platelets < 100,000 µl) studies without a reversible, identifiable cause
22. Evidence of tumor on screening of chest/abdominal/pelvic (body) CT scan
23. Any prior organ transplant
24. Being actively listed for, or under active consideration (i.e., work-up) for, a solid organ transplant of any kind
25. Known hypersensitivity to bovine products
26. Known hypersensitivity to dimethyl sulfoxide (DMSO)
27. Any malignancy within past 2 years (except for in-situ non-melanoma skin cancer and in-situ cervical cancer)
28. Any prior radiation therapy/treatment to the chest
29. Uncontrolled diabetes (HbA1 >9.0)
30. Any condition or other reason that, in the opinion of the Investigator or Medical Monitor, would render the subject unsuitable for the study

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Single Group Assignment

Masking: Quadruple Blind

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42 participants in 2 patient groups, including a placebo group

Allogeneic Cardiosphere-Derived Cells

Experimental group

Description:

The Phase I study consists of a Phase Ia portion and a Phase Ib portion. The Phase Ia portion (N=14 subjects) consists of an open-label, single-arm, study design. The potentially conducted Phase Ib portion of the study (N=28 subjects) consists of a double-blind, randomized, placebo-controlled study design. The Phase Ia portion is an open-label, dose escalation of Allogeneic Cardiosphere-Derived Cells (CDCs).

Treatment:

Biological: Allogeneic Cardiosphere-Derived Cells (CDCs)

Placebo

Placebo Comparator group

Description:

The placebo study arm only applies to the Phase Ib portion of the study design. The Phase Ia portion (N=14 subjects) consists of an open-label, single-arm, study design. The potentially conducted Phase Ib portion of the study (N=28 subjects) consists of a double-blind, randomized, placebo-controlled study design.

Treatment:

Biological: Allogeneic Cardiosphere-Derived Cells (CDCs)