Chronic advanced symptomatic heart failure secondary to ischemic cardiomyopathy MedDRA version: 18.0 Level: LLT Classification code 10010684 Term: Congestive heart failure System Organ Class: 100000004849
Conditions
Interventions
Product Name: C3BS-CQR-1
Product Code: C3BS-CQR-1
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Autologous bone marrow-derived cardiopoietic stem cells
CAS Number: N/A
Current Spons
Sponsors
Celyad SA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Eligible patients must meet all of the following inclusion criteria: 1. Age = 18 and 30. 5. Ability to perform a 6 minute walk test > 100 m and = 400 m. 6. History of hospitalization for HF within 12 months prior to screening or treatment in an out-patient clinic with intravenous vasoactive therapy (including vasodilators, positive inotropic agents and vasopressors) or diuretics for worsening HF within 12 months prior to screening. 7. Be or must have been within the previous 12 months in NYHA class III or IV or INTERMACS class 4, 5, 6 or 7 and at the time of inclusion, must be at least in NYHA class II or greater. 8. Use of ACE inhibitor and/or ARB; and beta blocker, for at least 3 months prior to screening visit, unless intolerant or contraindicated. 9. Stable dosing of ACE inhibitor, ARB, beta blocker, aldosterone blocker, and diuretics for at least one month prior to screening visit, defined as = 50% change in total dose of each agent. 10. Willing and able to give written informed consent. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 120 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 120
Exclusion criteria
Exclusion criteria: Eligible patients must meet none of the following exclusion criteria: 1. Women who are pregnant, confirmed by a positive urine or serum hCG laboratory test at screening. 2. Women of child-bearing potential without a negative serum or urine pregnancy test at screening or who are not practicing a reliable form of birth control. Women who are postmenopausal (12 months of spontaneous amenorrhea or 6 months of spontaneous amenorrhea with serum FSH level > 40 mIU/ml or 6 weeks post surgical bilateral oophorectomy) or surgically sterile are not considered to be of child-bearing potential. Reliable contraception includes surgical sterilization, hormonal contraception, or double-barrier methods. 3. Men refusing to exercise a reliable form of contraception. 4. Myocardial infarction, unstable angina or percutaneous coronary intervention (PCI) within 90 days prior to screening, or CABG surgery within 180 days prior to screening. 5. Patient on a cardiac transplant list or previously received any solid organ transplant. 6. Previously underwent cardiac surgery with remodeling procedure, left ventricular assist device placement or cardiomyoplasty. This exclusion does not apply to patients who underwent ventricularplasty without placements device >1 year ago. 7. Patient has undergone cardiac resynchronization therapy (CRT) within 6 months (180 days) prior to screening. 8. Severe uncontrolled HF requiring need for intensive intravenous diuretics or inotropic support within 1 month prior to screening. 9. Inability to perform a 6 minute walk test due to physical limitations other than HF including: (a.) Severe peripheral vascular disease (b.) Severe pulmonary disease or chronic obstructive pulmonary disease (COPD) limiting exercise (c.) Orthopedic limitations, severe muscular diseases, any other joint or muscular disease or neurological disorder (such as an old stroke or neuropathy) limiting the ability to walk for 6 minutes. 10. Dependence on chronic oral steroid therapy. 11. Stroke or transient ischemic attack leading to limitations in lower extremities or occurring within 180 days prior to screening. 12. Active myocarditis, constrictive pericarditis, restrictive, hypertrophic or congenital cardiomyopathy. 13. BMI 45. 14. Left ventricular thrombus. 15. Left ventricular wall thickness 3.0 mg/dL ( > 0.265 mmol/l) or is currently on dialysis. 23. Hematocrit < 28%. 24. Atherosclerosis and/or tortuosity of the aorta, iliac or femoral arteries of a degree that could impede or preclude the safe retrograde passage of the delivery catheter. 25. Chronic immunosuppressive therapy due to inflammatory or systemic disease. 26. Patient tested positive for HIV 1 or 2, Hepatitis B or C, HTLV 1 or 2 (if required by regulations) or syphilis. 27. Exposure to any previous experimental cell or angiogenic therapy and/or myocardial laser therapy and/or therapy with another investigational
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to evaluate the efficacy of C3BS-CQR-1 by comparing the overall response to C3BS-CQR-1 relative to standard of care undergoing a sham procedure using a composite outcome of morbidity and mortality, changes in quality of life , six-minute walk distance, and left ventricular structure and function at 39 weeks (9 months) post-procedure.;Secondary Objective: The secondary objective is to assess the safety of C3BS-CQR-1 by comparing the incidence of serious adverse events between study groups at 52 weeks (12 months) post-procedure and all cause mortality at 104 weeks (24 months) post-procedure. Additionally data will be collected to evaluate the safety and performance of the endoventricular injection catheter C-Cath® as a system for delivery of C3BS-CQR-1 into the left ventricular myocardium.;Timepoint(s) of evaluation of this end point: At 39 weeks (9 months) post index procedure.;Primary end point(s): The primary efficacy endpoint will measure the efficacy of C3BS-CQR-1 injection at 39 weeks (9 months) based on a hierarchical composite of: 1. All-cause mortality. 2. Worsening of heart failure events defined as requiring unscheduled treatment for signs and symptoms of heart failure in an urgent outpatient setting or requiring hospital admission, as adjudicated by a Clinical Events Committee. 3. Change in MLHFQ total score. 4. Change in Six-Minute Walk Test (6MWT). 5. Change in LVESV as assessed by echocardiography 6. Change in LVEF as assessed by echocardiography. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Safety endpoints will include the following: 1. All cause mortality through 104 weeks 2. The occurrence of the following clinical events through 52 and 104 weeks (12 and 24 months): cause of death, re-admissions and cause of re-admission, cardiac transplantation, myocardial infarction, stroke. Cause of death and occurrence of myocardial infarction and stroke will be as adjudicated by the CEC. 3. Aborted sudden death events through 39, 52, and 104 weeks (9, 12 and 24 months), defined as resuscitated sudden death or appropriate Automatic Implantable Cardioverter Defibrillator (AICD) therapy for severe ventricular tachyarrhythmias as adjudicated by a Clinical Event Committee. 4. Incidence of serious adverse events through 52 and 104 weeks (12 and 24 months) post index procedure. 5. Incidence of non-serious adverse events through 52 and 104 weeks (12 and 24 months) post index procedure. Secondary efficacy endpoints will include the effect of C3BS-CQR-1 injection at 52 weeks (12 months) on: 1. Time to the first occurrence of cardiovascular death or heart failure hospitalization. Tertiary (explorative) efficacy endpoints will include the effect of C3BS-CQR-1 injection on each of the components of the composite endpoint at 39, and 52 weeks (9 and 12 months) unless otherwise specified: 1. Time to all cause mortality. 2. Time to cardiovascular (CV) mortality. 3. Worsening of HF defined as requiring unscheduled treatment for signs and symptoms of heart failure in an urgentnoutpatient setting or requiring hospital admission, as adjudicated by a Clinical Events Committee. 4. Number of worsening heart failure events requiring urgent treatment in an urgent outpatient setting or requiring hospital admission. 5. Re-admission for heart failure as adjudicated by the Clinical Events Committee (CEC). 6. Hospital admission for a cardiovascular (CV) reason or death (for any cause) 7. Number of hospitalizations for CV reason or death 8. Death | — |
Countries
Belgium, Bulgaria, Croatia, Estonia, Hungary, Ireland, Israel, Italy, Lithuania, Poland, Serbia, Spain, Sweden, Switzerland, United Kingdom
Contacts
Public ContactClinical Trial Information
Celyad SA
Outcome results
None listed