Safety and Efficacy of Autologous Cardiopoietic Cells for Treatment of Ischemic Heart Failure. (CHART-1)

• ClinicalTrials.gov Identifier: NCT01768702
• Recruitment Status: Completed
• First Posted: January 15, 2013
• Last Update Posted: June 1, 2018
• Sponsor: Celyad Oncology SA
• Information provided by (Responsible Party): Celyad Oncology SA

Tracking Information

• First Submitted Date: December 21, 2012
• First Posted Date: January 15, 2013
• Last Update Posted Date: June 1, 2018
• Study Start Date: November 2012
• Actual Primary Completion Date: August 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 11, 2013)

Efficacy between groups post-index procedure [ Time Frame: 39 weeks post-index ]

Change between groups from baseline and 39 weeks in a hierarchical composite outcome comprising, from most to least severe outcome, days to death from any cause, number of worsening of heart failure events, change in score for the Minnesota Living with Heart Failure Questionnaire (MLHFQ) (10-point deterioration, no meaningful change,10-point improvement), change in six-minute walk distance (40-m deterioration, no meaningful change, 40-m improvement) and change in left ventricular end systolic volume (15-mL deterioration, no meaningful change, 15-mL improvement), and left ventricular ejection fraction (4% absolute deterioration, no meaningful change, 4% absolute improvement).

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: January 11, 2013)

Efficacy and safety between groups post-index procedure [ Time Frame: 52 and 104 weeks post-index ]

Safety: Number and cause of deaths and re-admissions, number of cardiac transplantations, number of myocardial infarctions, number of strokes. Incidence of serious adverse events (AE) through week 104 and non-serious AEs (through week 52). Efficacy: Time to all cause mortality, time to worsening of heart failure, and time to aborted sudden death through week 52.

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: January 11, 2013)

Efficacy and safety between groups post-index procedure [ Time Frame: 39 and 52 weeks post-index ]

Time to all cause mortality, time to cardiovascular mortality, and rate of worsening heart failure requiring outpatient IV therapy for heart failure or readmission for heart failure, and others.

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: Safety and Efficacy of Autologous Cardiopoietic Cells for Treatment of Ischemic Heart Failure.
• Official Title: Efficacy and Safety of Bone Marrow-derived Mesenchymal Cardiopoietic Cells (C3BS-CQR-1) for the Treatment of Chronic Advanced Ischemic Heart Failure.
• Brief Summary: Evaluation the safety and efficacy of C3BS-CQR-1 by comparing the overall response to standard of care and C3BS-CQR-1 relative to standard of care and a sham procedure.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Heart Failure

Intervention

• Biological: Injection of C3BS-CQR-1
  Injection of the C3BS-CQR-1 using the C-Cath® injection catheter.
• Biological: Sham, no injection
  Mimic the injection procedure trough insertion of a sham catheter. No injection actually performed

Study Arms

• Sham Comparator: Control
  Sham, no injection
  Intervention: Biological: Sham, no injection
• Experimental: C3BS-CQR-1 Treated
  Injection of C3BS-CQR-1
  Intervention: Biological: Injection of C3BS-CQR-1

• Publications *: Bartunek J, Davison B, Sherman W, Povsic T, Henry TD, Gersh B, Metra M, Filippatos G, Hajjar R, Behfar A, Homsy C, Cotter G, Wijns W, Tendera M, Terzic A. Congestive Heart Failure Cardiopoietic Regenerative Therapy (CHART-1) trial design. Eur J Heart Fail. 2016 Feb;18(2):160-8. doi: 10.1002/ejhf.434. Epub 2015 Dec 14.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 7, 2017): 315
• Original Estimated Enrollment (submitted: January 11, 2013): 240
• Actual Study Completion Date: August 2017
• Actual Primary Completion Date: August 2017 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

Eligible patients must meet all of the following inclusion criteria:

1. Age ≥ 18 and < 80 years.
2. Systolic dysfunction with left ventricular ejection fraction (LVEF) ≤ 35% as assessed by echocardiography.
3. Ischemic heart failure without known need for revascularization.
4. Total MLHFQ score > 30.
5. Ability to perform a 6 minute walk test > 100 m and ≤ 400 m.
6. History of hospitalization for heart failure (HF) within 12 months prior to screening or treatment in an outpatient clinic with intravenous vasoactive therapy (including vasodilators, positive inotropic agents and vasopressors) or diuretics for worsening Heart Failure within 12 months prior to screening.
7. Be or must have been within the previous 12 months in New York Heart Association (NYHA) Class III or IV or Interagency Registry for Mechanically Assisted Circulatory Support (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 angiotensin receptor blocker (ARB); and beta blocker, for at least 3 months prior to screening visit, unless intolerant or contraindicated.
9. Stable dosing of ACE inhibitor, angiotensin receptor blocker , 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.

Exclusion Criteria (summarized):

Eligible patients must meet none of the following exclusion criteria:

1. Women who are pregnant, confirmed by a positive urine or serum human chorionic gonadotropin laboratory test at screening.
2. Women of child-bearing potential without a negative serum or urine pregnancy test at screening. 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 doublebarrier 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 coronary artery bypass graft 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 placement device more than one year ago.
7. Patient has undergone cardiac resynchronization therapy within 6 months 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:

   1. Severe peripheral vascular disease
   2. Severe pulmonary disease or chronic obstructive pulmonary disease limiting exercise
   3. 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 < 19 or > 45.
14. Left ventricular thrombus.
15. Left ventricular (LV) wall thickness < 8mm visualized in more than 50% of LV, and defined as a "LV no-go zone".
16. LV aneurysm or candidate for surgical aneurysmectomy.
17. Sustained ventricular tachycardia or ventricular fibrillation which led to automatic implantable cardioverter/defibrillator (AICD) therapy (shock) within 3 months prior to screening.
18. Primary significant organic valvular heart disease.
19. Moderate to severe aortic valve disease precluding catheter entry into the LV.
20. Mechanical prosthetic valve in aortic or mitral position.
21. Chronic infection or active malignancy.
22. Patient has compromised renal function as reflected by a serum creatinine level >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, human T-cell lymphotrophic virus (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 drug within 60 days prior to screening or enrollment in any concurrent study that may confound the results of this study.
28. Known drug or alcohol dependence or any other factors which will interfere with the study conduct or interpretation of the results or in the opinion of the investigator are not suitable to participate.
29. Any illness other than congestive heart failure which might reduce life expectancy to less than 2 years from screening.
30. Known and relevant allergies and/or hypersensitivities to Dextran or other plasma volume expanders to include Gentran, Hyskon and Macrodex.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium, Bulgaria, Hungary, Israel, Italy, Poland, Serbia, Spain, Switzerland
• Removed Location Countries: Sweden, United Kingdom

Administrative Information

• NCT Number: NCT01768702
• Other Study ID Numbers: C3BS-C-11-01; 2011-001117-13 ( EudraCT Number )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Celyad Oncology SA
• Original Responsible Party: Same as current
• Current Study Sponsor: Celyad Oncology SA
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Chair: André Terzic, MD; Mayo Clinic, Division of Cardiovascular Diseases, Rochester (MN, USA)
• Study Chair: Jozef Bartunek, MD; OLV Ziekenhuis Aalst (Belgium)

• PRS Account: Celyad Oncology SA
• Verification Date: May 2018