Clinical Trials

Date: 2015-12-21

Type of information: Clinical trial authorization

phase: 3

Announcement: clinical trial authorization

Company: Celyad (Belgium)

Product: C-Cure®( C3BS-CQR-1)

Action mechanism:

• cell therapy/stem cell therapy. C-Cure®/C3BS-CQR-1 is an autologous stem cell therapy for heart failure. This therapy involves taking cells from a patient’s bone marrow and through a proprietary process called Cardiopoiesis, re-programming those cells so that they become heart precursor cells with the aim of replicating the normal process of cardiac development in the embryo and healing the failing heart. The cells, known as cardiopoietic cells, are then injected back into the patient’s heart through a minimally invasive procedure using a proprietary catheter called C-Cath®ez, with the goal of repairing damaged tissue and improving heart function, clinical outcomes and quality of life.
•  C3BS-CQR-1 is the outcome of multiple years of research conducted at Mayo Clinic (Rochester, Minnesota, USA), Cardio3 BioSciences (Mont-Saint-Guibert, Belgium) and Cardiovascular Centre in Aalst (Aalst, Belgium).

Disease: heart failure

Therapeutic area: Cardiovascular diseases

Country: Belgium, Hungary, Israel, Italy, Poland, Serbia, Spain, Sweden, Switzerland, UK, USA

Trial details:

• The first Phase III study, CHART-1 (Congestive Heart Failure Cardiopoietic Regenerative Therapy 1) is a prospective, multi-centre, randomized, sham-controlled, patient-and evaluator-blinded study comparing treatment with C3BS-CQR-1 to a sham treatment. The trial has recruited 240 patients with chronic advanced symptomatic heart failure in Europe and Israel. The primary endpoint of the trial is a composite endpoint including mortality, morbidity, quality of life, Six Minute Walk Test and left ventricular structure and function at 9 months post-procedure. Studies in additional countries will commence once national regulatory approvals have been received.(NCT01768702)
• CHART-2 is designed as a prospective, multi-centre, randomized, sham-controlled, patient-and evaluator-blinded study comparing treatment with C3BS-CQR-1 to a sham treatment. The trial is aimed to recruit a minimum of 240 patients with chronic advanced symptomatic heart failure. The primary endpoint of the trial is the Six Minute Walk Test post-procedure, a commonly used index of cardiovascular performance. (NCT02317458)

Latest news:

• • On December 21, 2015, Celyad announced that the FDA has authorized the Company’s Investigational New Drug (IND) application to proceed thus allowing for the clinical testing of Celyad’s lead cardiology candidate (C-Cure cardiopoietic cells) delivered via the proprietary catheter (C-Cathez) in the Phase III Heart Failure Trial (CHART-2) in the US.
• • On December 16, 2015, Celyad announced that a methods paper on the CHART-1 clinical trial design has been published in the European Journal of Heart Failure .
• • On August 3, 2015, Celyad, previously known as Cardio3 Bioscience, announced that it has completed the injection procedure for the last patient enrolled in CHART-1, its European Phase III clinical trial for its lead cardiovascular disease product candidate, C-Cure®. With the final injection procedure completed, Celyad has initiated the nine-month follow-up period for this patient. The Company expects to release the full clinical data set for CHART-1 in the middle of 2016. C-Cure®’s potential has been demonstrated in a multi-centre randomized controlled Phase II trial conducted in Europe. The results of the C-Cure® Phase II trial were published in April 2013 in the Journal of American College of Cardiology.
• • On March 30, 2015, Cardio3 BioSciences,announced the successful completion of a futility analysis for C-Cure®, its lead cell therapy for congestive heart failure, currently being evaluated in a Phase III clinical trial in Europe and Israel (CHART-1).The Data Safety and Monitoring Board (DSMB) reviewed unblinded safety and efficacy data from CHART-1 and determined that such data did not support discontinuation of the trial on the basis of safety or futility and recommended that it continue without changes to the protocol. The DSMB analysis was performed after all patients were enrolled in the trial. Prior to this futility analysis, CHART-1 completed all safety data reviews by the DSMB, indicating that there is no major or unexpected safety concern with C-Cure® in the target patient population. The next milestone in the clinical trial will be the release of the full clinical data set, anticipated for the middle of 2016.
• • On December 19, 2014, Cardio3 BioSciences announced the enrolment of the 240th patient in its CHART-1 European trial for C-Cure®. With recruitment that started in mid-2013, Cardio3 BioSciences has enrolled 240 patients in less than 18 months, ahead of schedule. As usual in clinical trials targeting severe indications, the company will continue to recruit additional patients in anticipation of patient dropouts. The CHART-1 trial is currently ongoing in 12 countries in Europe and Israel. Interim futility readout scheduled for the end of March 2015 and the readout of the full dataset a year later.
• • On November 26, 2014, Cardio3 BioSciences announced the appointment of its three Co-Principal Investigators for the CHART-2 study (Congestive Heart Failure cArdiopoietic Regenerative Therapy), authorized in the United States by the FDA in January, and anticipated to start by the end of 2014.
• • On October 13, 2014, Cardio3 BioSciences announced it has received authorization from Swissmedic, the Swiss agency for the authorisation and supervision of therapeutic products, to begin its CHART-1 European Phase III trial for C-Cure® in Switzerland. After the recent authorization in Bulgaria, and earlier in Sweden, Ireland, the United Kingdom, Belgium, Israel, Serbia, Hungary, Spain, Italy, and Poland, Switzerland is the 12th country to have authorized this unique study, which aims to treat ischemic congestive heart failure. Now in the final stages of this clinical trial, and with recruitment continuing to be strong, Cardio3 BioSciences is expected to finalize the recruitment of the last patients towards end of 2014. In parallel, CHART-2, the FDA-approved Phase III clinical trial, will also start around the end of the year.
• • On September 15, 2014, Cardio3 BioSciences announced it has received the recommendation of the Data Safety and Monitoring Board (DSMB) to continue the CHART-1 clinical trial according to the original protocol. The recommendation is based on a planned analysis performed on all patient safety data available as per mid-August 2014. The members of the DSMB approved unanimously the continuation of the trial having concluded that one month post treatment, C-Cure® and C-Cathez® shows no safety issue that compromises the continuation of the CHART-1 Phase III study.
• • On June 10, 2014, Cardio3 BioSciences announced it has received authorization from the Swedish Medical Products Agency (LÄKEMEDELSVERKET) to begin its CHART-1  trial for C-Cure® in Sweden.
• • On April 10, 2014, Cardio3 BioSciences has announced it has received authorization from the Irish Medicines Board (IMB) to begin its CHART-1 trial for C-Cure® in Ireland. .
• • On January 9, 2014, Cardio3 BioSciences has announced that the FDA has authorized the Company's Investigational New Drug (IND) application for clinical testing of C-Cure® as a treatment targeting heart failure. CHART-2 is intended to assess in the US, the efficacy of C3BS-CQR-1 as a treatment for heart failure of ischemic origin. Phase II data published in JACC1 showed C3BS-CQR-1 statistically significant improvement of 77m in six-minute walk distance for the treated patients compared to the control group (p<0.01), which represented a 20% improvement for treated patients versus the control group.
• • On October 23, 2013, Cardio3 BioSciences has announced it has received authorization from the Italian Medicines Agency (AIFA) to begin its Congestive Heart failure Cardiopoietic Regenerative Therapy (CHART-1) European Phase III trial for C-Cure® in Italy.
• • On September 30, 2013, Cardio3 BioSciences has announced it has received authorization from the Spanish Agency for Medicines and Health Products (AEMPS) to begin its CHART-1 trial for C-Cure® in Spain. To date, 11 internationally-renowned centers have begun recruiting patients in those countries.
• • On June 10, 2013, Cardio3 BioSciences has announced it has treated its first  patients in the CHART-1 trial for C-Cure®. The patients, who have been randomly allocated to either the treatment or sham arm of the trial, were treated at the CHU Charleroi, Belgium.
• • On November 22, 2012,  Cardio3 BioSciences  has received authorization from the Belgian Federal Agency for Medicines and Health Products (FAMHP) to begin its CHART-1 Phase III trial for C3BS-CQR-1 in Belgium. Studies in additional countries will commence once national regulatory approvals have been received. This represents a world premiere for a regenerative medicine product targeting heart failure to be tested in the context of a Phase III trial. This Phase III trial builds on the successful outcome of the Phase II trial conducted between 2009 and 2010 in multiple clinical sites in Belgium, Serbia and Switzerland.

Is general: Yes