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

A Randomized, Double-blind, Placebo-controlled, Phase I Study of the Safety of Multi-vessel Intra-coronary Delivery of Allogeneic Human Cardiosphere-Derived Stem Cells in Patients With Dilated Cardiomyopathy (DCM)

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.

Study Overview

• Status: Unknown
• Conditions: Heart Failure; Ischemic Cardiomyopathy; Nonischemic Cardiomyopathy; Dilated Cardiomyopathy (DCM)
• Intervention / Treatment: Biological: Allogeneic Cardiosphere-Derived Cells (CDCs)

Detailed 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.

• Study Type: Interventional
• Enrollment (Anticipated): 42
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Allogeneic Cardiosphere-Derived Cells; 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).	Biological: Allogeneic Cardiosphere-Derived Cells (CDCs); Intracoronary delivery of CAP-1002 or placebo; Other Names: CAP-1002
Placebo Comparator: Placebo; 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.	Biological: Allogeneic Cardiosphere-Derived Cells (CDCs); Intracoronary delivery of CAP-1002 or placebo; Other Names: CAP-1002

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Proportion of subjects that experience new TIMI flow 0-2 or TIMI myocardial perfusion grade (TMPG) 0-2.	Intraprocedural
Proportion of subjects that experience acute myocarditis, possibly attributable to CAP-1002. In order to be considered related to CAP-1002, humoral or cellular or immune reaction specific to CAP-1002 must also be documented.	Within one month of intracoronary infusion
Proportion of subjects that experience ventricular tachycardia or ventricular fibrillation resulting in death, appropriate discharge of an ICD or requiring medical intervention.	During or within 72 hours of intracoronary infusion
Proportion of subjects that experience sudden unexpected death occurring within one hour of symptom onset, or un-witnessed death in a person previously observed to be well within the preceding 24 hours without an identified cause.	During or within 72 hours of intracoronary infusion
Proportion of subjects that experience major adverse cardiac events (MACE), including death, non-fatal myocardial infarction and re-hospitalization for cardiovascular event (including heart failure hospitalizations).	During or within 72 hours of intracoronary infusion

Secondary Outcome Measures

Outcome Measure	Time Frame
Acute myocarditis possibly attributable to CAP-1002. In order to be considered related to CAP-1002, humoral or cellular immune reaction specific to CAP-1002 must also be documented.	During the six & twelve month follow-up period
Ventricular tachycardia or ventricular fibrillation resulting in death or requiring medical intervention or appropriate discharge of an ICD.	During the six & twelve month follow-up period
Sudden unexpected death defined as occurring within one hour of symptom onset, or unwitnessed death in a person previously observed to be well within the preceding 24 hours without an identified cause.	During the six & twelve month follow-up period
Major adverse cardiac events (MACE), including death, non-fatal myocardial infarction, hospitalization for cardiovascular event, emergency room treatment for heart failure, left ventricular assist device or heart transplant.	During the six & twelve month follow-up period
Any hospitalization due to a cardiovascular cause or related to CAP-1002 (or placebo in Phase Ib).	During the six & twelve month follow-up period
Any inter-current cardiovascular illness or one related to CAP-1002 (or placebo in Phase Ib) which prolongs hospitalization.	During the six & twelve month follow-up period
Development of, or an increase in the frequency of, VT with a duration of 30 seconds or longer ascertained by protocol-mandated ECG ambulatory monitoring.	During the six & twelve month follow-up period
Development of increased anti-Human Leukocyte Antigen (HLA) antibody levels with development of sensitization to HLA antigens specific to the CAP-1002 CDC donor at immunologically significant titers.	During the six & twelve month follow-up period
Total number of appropriate ICD firings.	During the six & twelve month follow-up period
Peak elevation in troponin and CKMB levels following CAP-1002 or placebo infusion.	Through Month 1

Collaborators and Investigators

• Sponsor: Capricor Inc.
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); National Institutes of Health (NIH); Cedars-Sinai Medical Center
• Investigators: Principal Investigator: Rajendra (Raj) Makkar, MD, Cedars-Sinai Medical Center, Heart Institute

Publications and helpful links

Helpful Links

• Capricor's website

Study record dates

Study Major Dates

• Study Start: November 1, 2014
• Primary Completion (Actual): May 1, 2015
• Study Completion (Anticipated): April 1, 2020

Study Registration Dates

• First Submitted: November 5, 2014
• First Submitted That Met QC Criteria: November 14, 2014
• First Posted (Estimate): November 18, 2014

Study Record Updates

• Last Update Posted (Estimate): June 21, 2016
• Last Update Submitted That Met QC Criteria: June 17, 2016
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Keywords: cardiovascular diseases; heart failure; adult stem cells; cardiomyopathy; heart disease; ventricular dysfunction; pathological processes; cardiosphere-derived stem cells; intracoronary infusion
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Genetic Diseases, Inborn; Cardiomegaly; Laminopathies; Heart Failure; Cardiomyopathies; Cardiomyopathy, Dilated
• Other Study ID Numbers: CAP-1002 (DYNAMIC); R44HL095203 (U.S. NIH Grant/Contract)