We are updating the design of this site. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02293603
First Posted: November 18, 2014
Last Update Posted: June 21, 2016
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborators:
Cedars-Sinai Medical Center
National Institutes of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Capricor Inc.
  Purpose
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.

Condition Intervention Phase
Dilated Cardiomyopathy (DCM) Ischemic Cardiomyopathy Nonischemic Cardiomyopathy Heart Failure Biological: Allogeneic Cardiosphere-Derived Cells (CDCs) Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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)

Resource links provided by NLM:


Further study details as provided by Capricor Inc.:

Primary Outcome Measures:
  • Proportion of subjects that experience new TIMI flow 0-2 or TIMI myocardial perfusion grade (TMPG) 0-2. [ Time Frame: 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. [ Time Frame: 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. [ Time Frame: 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. [ Time Frame: 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). [ Time Frame: During or within 72 hours of intracoronary infusion ]

Secondary Outcome Measures:
  • 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. [ Time Frame: 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. [ Time Frame: 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. [ Time Frame: 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. [ Time Frame: 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). [ Time Frame: 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. [ Time Frame: 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. [ Time Frame: 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. [ Time Frame: During the six & twelve month follow-up period ]
  • Total number of appropriate ICD firings. [ Time Frame: During the six & twelve month follow-up period ]
  • Peak elevation in troponin and CKMB levels following CAP-1002 or placebo infusion. [ Time Frame: Through Month 1 ]

Estimated Enrollment: 42
Study Start Date: November 2014
Estimated Study Completion Date: April 2020
Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: CAP-1002

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.
  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02293603


Locations
United States, California
Cedars-Sinai Medical Center
Los Angeles, California, United States, 90048
Sponsors and Collaborators
Capricor Inc.
Cedars-Sinai Medical Center
National Institutes of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
Principal Investigator: Rajendra (Raj) Makkar, MD Cedars-Sinai Medical Center, Heart Institute
Study Director: Deborah Ascheim, MD Capricor Inc.
  More Information

Additional Information:
Responsible Party: Capricor Inc.
ClinicalTrials.gov Identifier: NCT02293603     History of Changes
Obsolete Identifiers: NCT01815060
Other Study ID Numbers: CAP-1002 (DYNAMIC)
R44HL095203 ( U.S. NIH Grant/Contract )
First Submitted: November 5, 2014
First Posted: November 18, 2014
Last Update Posted: June 21, 2016
Last Verified: June 2016

Keywords provided by Capricor Inc.:
cardiomyopathy
cardiosphere-derived stem cells
intracoronary infusion
adult stem cells
heart disease
ventricular dysfunction
pathological processes
cardiovascular diseases
heart failure

Additional relevant MeSH terms:
Heart Failure
Cardiomyopathies
Cardiomyopathy, Dilated
Heart Diseases
Cardiovascular Diseases
Cardiomegaly