Safety and Efficacy of Autologous Cardiopoietic Cells for Treatment of Ischemic Heart Failure.

Heart Failure Clinical Trial

— CHART-1  

Official title:

Efficacy and Safety of Bone Marrow-derived Mesenchymal Cardiopoietic Cells (C3BS-CQR-1) for the Treatment of Chronic Advanced Ischemic Heart Failure.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01768702
• Other study ID #: C3BS-C-11-01
• Secondary ID: 2011-001117-13
• Status: Completed
• Phase: Phase 3
• Start date: November 2012
• Est. completion date: August 2017

Study information

• Verified date: May 2018
• Source: Celyad (formerly named Cardio3 BioSciences)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 315
• Est. completion date: August 2017
• Est. primary completion date: August 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Heart Failure

Intervention

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

Locations

Country	Name	City	State
Belgium	OLV Ziekenhuis Aalst	Aalst
Belgium	Centre Hospitalier Universitaire de Liège	Liège
Belgium	Hopital Civil Marie Curie	Lodelinsart
Belgium	AZ Glorieux	Ronse
Belgium	CHU Mont-Godinne	Yvoir
Bulgaria	City Clinic Cardiology Center Multiprofile Hospital for Active Treatment	Sofia
Bulgaria	Multiprofile Hospital for Active Treatment 'Tokuda Hospital Sofia'	Sofia
Bulgaria	University Multiprofile Hospital for Active Treatment 'Alexandrovska' EAD	Sofia
Hungary	Gottsegen György Országos Kardiológiai Intézet - Felnott Kardiológiai Osztály	Budapest
Hungary	MH Egészségügyi Központ Kardiológiai Osztály	Budapest
Hungary	Semmelweis Egyetem - Városmajori Szív- és Érgyógyászati Klinika	Budapest
Hungary	Debreceni Egyetem Orvos - és Egészségtudomanyi Centrum	Debrecen
Hungary	Pécsi Tudományegyetem Klinikai Központ - Szívgyógyászati Klinika	Pécs
Israel	Barzilai Medical Center - Cardiology Unit	Ashkelon
Israel	Hillel Yaffe Medical Center	Hadera
Israel	Western Galilee Hospital	Nahariya
Israel	Nazareth Hospital EMMS	Nazareth
Israel	Ziv Medical Center - Heart Institute	Safed
Italy	A.O. Spedali Civili di Brescia	Brescia
Italy	AOUI Verona - Borgo Trento Hospital	Verona
Poland	Uniwersyteckie Centrum Kliniczne, KliniczneCentrum Kardiologii	Gdansk
Poland	Górnoslaskie Centrum Medyczne Slaskiej Akademii Medycznej	Katowice
Poland	Krakowski Szpital Specjalistyczny im. Jana Pawla II w Krakowie	Kraków
Poland	Bieganski Hospital	Lódz
Serbia	Clinic of Emergency Internal Medicinne Military Medical Academy	Belgrade
Serbia	Clinical Center of Serbia - Cardiology Clinic	Belgrade
Serbia	Clinical Centre of Serbia, Cardiology Clinic	Belgrade
Serbia	Clinical Hospital Center Bezanijska Kosa, Cardiology Dept.	Belgrade
Serbia	Clinical Hospital Center Zvezdara - Cardiology Clinic	Belgrade
Serbia	Clinical Center of Kragujevac,	Kragujevac
Spain	Hospital Universitario Germans Trias i Pujol	Barcelona
Spain	Hospital Clinico San Carlos	Madrid
Spain	Hospital General Universitario Gregorio Marañon	Madrid
Spain	Hospital Clinico Universitario Virgen de la Victoria - Campus de Teatinos s/n	Malaga
Switzerland	Cardiocentro Ticino	Lugano

Sponsors (1)

Lead Sponsor	Collaborator
Celyad (formerly named Cardio3 BioSciences)

Countries where clinical trial is conducted

Belgium,  Bulgaria,  Hungary,  Israel,  Italy,  Poland,  Serbia,  Spain,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Efficacy and safety between groups post-index procedure	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.	39 and 52 weeks post-index
Primary	Efficacy between groups post-index procedure	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).	39 weeks post-index
Secondary	Efficacy and safety between groups post-index procedure	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.	52 and 104 weeks post-index