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)
试验速览
- 阶段
- 1 期
- 入组人数
- 42
- 试验地点
- 2
- 主要终点
- Proportion of subjects that experience new TIMI flow 0-2 or TIMI myocardial perfusion grade (TMPG) 0-2.
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
结局指标
主要结局
Proportion of subjects that experience new TIMI flow 0-2 or TIMI myocardial perfusion grade (TMPG) 0-2.
时间窗: 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.
时间窗: 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.
时间窗: 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).
时间窗: 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.
时间窗: During or within 72 hours of intracoronary infusion
次要结局
- 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)
- 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)
- 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)
- 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)
- Total number of appropriate ICD firings.(During the six & twelve month follow-up period)
- 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)
- 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)
- Peak elevation in troponin and CKMB levels following CAP-1002 or placebo infusion.(Through Month 1)