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

Primary Purpose

Dilated Cardiomyopathy (DCM), Ischemic Cardiomyopathy, Nonischemic Cardiomyopathy

Status

Unknown status

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Allogeneic Cardiosphere-Derived Cells (CDCs)

About this trial

This is an interventional treatment trial for Dilated Cardiomyopathy (DCM) focused on measuring cardiomyopathy, cardiosphere-derived stem cells, intracoronary infusion, adult stem cells, heart disease, ventricular dysfunction, pathological processes, cardiovascular diseases, heart failure

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Major Inclusion Criteria:

DCM with left ventricular ejection fraction (LVEF) ≤ 35% as determined by a historical TTE within the previous 6 months
New York Heart Association (NYHA) Class III or ambulatory Class IV heart failure
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
Coronary anatomy suitable for Investigational Product (IP) infusion, as determined by the Eligibility Committee (a team of cardiology experts)
Ability to provide informed consent and follow-up with protocol procedures
Screening cardiac CT left ventriculogram ejection fraction <40% with left ventricular dilatation
Age ≥ 18 years

Major Exclusion Criteria:

Diagnosis of active myocarditis
Immunologic incompatibility with all available Master Cell Banks (MCBs) by single-antigen bead (SAB) serum antibody profiling
Left Ventricular Assist Devices (LVAD) or those actively in the process of acquiring one
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
History of sustained ventricular tachycardia (VT) requiring cardiopulmonary resuscitation (with the exception of subjects who subsequently received an ICD)
Non-cardiovascular disease with life expectancy of < 3 years
Known hypersensitivity to contrast agents
Estimated glomerular filtration rate (GFR) < 50 mL/min
Active infection not responsive to treatment
Active allergic reactions, connective tissue disease or autoimmune disorders
History of cardiac tumor, or cardiac tumor demonstrated on screening
History of previous stem cell therapy
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)
History of receipt of chemotherapeutic agents known to be implicated in cardiac dysfunction [Adriamycin, trastuzumab (Herceptin)]
Known moderate-severe aortic stenosis/insufficiency or severe mitral stenosis/regurgitation
Participation in an on-going protocol studying an experimental drug or device
Current active alcohol or drug abuse or inability to comply with protocol-related procedures
Pregnant/nursing women and women of child-bearing potential without use of active and highly reliable contraception
Known history of Human Immunodeficiency Virus (HIV) infection
Known history of chronic viral hepatitis
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
Evidence of tumor on screening of chest/abdominal/pelvic (body) CT scan
Any prior organ transplant
Being actively listed for, or under active consideration (i.e., work-up) for, a solid organ transplant of any kind
Known hypersensitivity to bovine products
Known hypersensitivity to dimethyl sulfoxide (DMSO)
Any malignancy within past 2 years (except for in-situ non-melanoma skin cancer and in-situ cervical cancer)
Any prior radiation therapy/treatment to the chest
Uncontrolled diabetes (HbA1 >9.0)
Any condition or other reason that, in the opinion of the Investigator or Medical Monitor, would render the subject unsuitable for the study

Sites / Locations

Cedars-Sinai Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Allogeneic Cardiosphere-Derived Cells

Placebo

Arm 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).

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.

Outcomes

Primary Outcome Measures

Proportion of subjects that experience new TIMI flow 0-2 or TIMI myocardial perfusion grade (TMPG) 0-2.

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.

Proportion of subjects that experience ventricular tachycardia or ventricular fibrillation resulting in death, appropriate discharge of an ICD or requiring medical intervention.

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.

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).

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.

Ventricular tachycardia or ventricular fibrillation resulting in death or requiring medical intervention or appropriate discharge of an ICD.

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.

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.

Any hospitalization due to a cardiovascular cause or related to CAP-1002 (or placebo in Phase Ib).

Any inter-current cardiovascular illness or one related to CAP-1002 (or placebo in Phase Ib) which prolongs hospitalization.

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.

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.

Total number of appropriate ICD firings.

Peak elevation in troponin and CKMB levels following CAP-1002 or placebo infusion.

Full Information

NCT ID

NCT02293603

First Posted

November 5, 2014

Last Updated

June 17, 2016

Sponsor

Capricor Inc.

Collaborators

Cedars-Sinai Medical Center, National Institutes of Health (NIH), National Heart, Lung, and Blood Institute (NHLBI)

1. Study Identification

Unique Protocol Identification Number

NCT02293603

Brief Title

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

Acronym

DYNAMIC

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)

Study Type

Interventional

2. Study Status

Record Verification Date

June 2016

Overall Recruitment Status

Unknown status

Study Start Date

November 2014 (undefined)

Primary Completion Date

May 2015 (Actual)

Study Completion Date

April 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Capricor Inc.

Collaborators

Cedars-Sinai Medical Center, National Institutes of Health (NIH), National Heart, Lung, and Blood Institute (NHLBI)

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Dilated Cardiomyopathy (DCM), Ischemic Cardiomyopathy, Nonischemic Cardiomyopathy, Heart Failure

Keywords

cardiomyopathy, cardiosphere-derived stem cells, intracoronary infusion, adult stem cells, heart disease, ventricular dysfunction, pathological processes, cardiovascular diseases, heart failure

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

42 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Allogeneic Cardiosphere-Derived Cells

Arm Type

Experimental

Arm Description

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Intervention Type

Biological

Intervention Name(s)

Allogeneic Cardiosphere-Derived Cells (CDCs)

Other Intervention Name(s)

CAP-1002

Intervention Description

Intracoronary delivery of CAP-1002 or placebo

Primary Outcome Measure Information:

Title

Proportion of subjects that experience new TIMI flow 0-2 or TIMI myocardial perfusion grade (TMPG) 0-2.

Time Frame

Intraprocedural

Title

Time Frame

Within one month of intracoronary infusion

Title

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

Title

Time Frame

During or within 72 hours of intracoronary infusion

Title

Time Frame

During or within 72 hours of intracoronary infusion

Secondary Outcome Measure Information:

Title

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