Safety and Efficacy Evaluation of Intracoronary Infusion of Allogeneic Human Cardiac Stem Cells in Patients With AMI

NCT02439398 | Completed Phase 1 DMC

• 1 other identifier: CTPX01
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 1

Brief Summary

Development of myocardial reparative therapy for the treatment of acute ischemic cardiac disease, based on the intracoronary administration of allogeneic Cardiac Stem Cells (CSCs) to ameliorate myocardial cell death and promote cardio-regeneration. The study comprises two phases:

1. 1.Initial dose-escalation open-label safety phase comprising 6 patients. Escalation will start with the Maximum Recommended Safe Dose (MRSD) calculated from Non-Observed Adverse Events Level (NOAEL) and it is expected to finish with the target dose (TD). There will be no placebo group for this initial phase.
2. 2.Randomized double-blind placebo-controlled safety and efficacy phase in which the TD will be injected if the dose-escalation phase is completed successfully.

Conditions

Acute Myocardial Infarction

Outcome Measures

Primary Outcomes (1)

• Safety measured as the number of deaths and number of Major Adverse Cardiac Events (MACE)

  The primary objective is to demonstrate the safety of the intra-coronary infusion of allogeneic cardiac stem cells in patients with a 7 days evolution first myocardial infarction and left ventricle dysfunction. Safety will be assessed a) evaluating the number of deaths from any cause within 30 days after cell medicine administration; b) evaluating the number of Major Adverse Cardiac Events (MACE) during the first 30 days (composite endpoint), defined as death from any cause, new Acute Myocardial Infarction (AMI), hospitalization due to Heart Failure (HF), sustained Ventricular Tachycardia (VT), Ventricular Fibrillation (VF), and stroke within 12 months after cell medicine administration.

  12 months

Secondary Outcomes (3)

• Efficacy measured by MRI as the infarct size change

  6 and 12 months

• Efficacy measured by MRI as the evolution of biomechanical parameters

  6 and 12 months

• Efficacy measured by MRI as the evolution of edema

  1 month

Study Arms (2)

Allogeneic human cardiac stem cells

EXPERIMENTAL

After randomization, subjects will received a suspension of allogeneic human cardiac stem cells (35 millions of CSCs - cell medicine) infused into the coronary artery responsible for the ischemic event.

Biological: Allogeneic human cardiac stem cells (CSCs)

Placebo: Human Serum Albumin-HSA 5%

PLACEBO COMPARATOR

After randomization, subjects will received placebo (which is also the cell medicine diluent). The placebo consists of a final administered volume of human serum albumin 5% in saline solution equivalent to the reconstituted cell medicine (18 mL). The placebo to be used is a marketed product (HSA 5%).

Other: Human Serum Albumin-HSA 5%

Interventions

Allogeneic human cardiac stem cells (CSCs) BIOLOGICAL

Allogeneic human CSCs is a new cell medicine based on cells isolated from human heart biological samples (right atrium appendage of donors) and expanded in vitro.

Also known as: AlloCSC-01

Allogeneic human cardiac stem cells

Human Serum Albumin-HSA 5% OTHER

Human Serum Albumin (HSA) is a well-known physiologic protein widely used in clinical practice and without known toxicity after parenteral administration.

Placebo: Human Serum Albumin-HSA 5%

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult patients ≥ 18 years of age and ≤ 80 years.
• Patients presenting a ST-segment-elevation myocardial infarction (STEMI) according to the universally accepted definition found in the STEMI management guide of the European Society of Cardiology
• Killip ≤ 2 on admission
• Successful primary coronary revascularization by Percutaneous Coronary Intervention- PCI - (Thrombolysis In Myocardial Infarction \[TIMI\] = 3) within 12h after the onset of infarct symptoms
• Bare-metal or drug-eluting stents (DES) of second generation (including new second generation stents, e.g. biolimus, novolimus and bioreabsorbable stents) at coronary revascularization by PCI
• The affected coronary artery is adequate for cells infusion at the administration time. The administration procedure is technically feasible on day 4-7 after coronary revascularization by PCI
• The patient is stable and in adequate clinical condition to undergo the procedure.

You may not qualify if:

• Participation in another clinical trial in the last 30 days
• Previous allogeneic transplant (blood transfusions are allowed) or treated with cell or gene therapy
• Previous Q-wave infarction
• Significant valve disease, relapsing pericarditis, history of cardiac tamponade, cardiomyopathies
• Severe stenotic lesions (\>90%) in a coronary vessel with size \>2.75 mm not treated by PCI at least 24 hours before the baseline MRI study
• Previous EF≤45%, NYHA \> 2 (New York Heart Association Functional Classification) or hospital admission for heart failure before STEMI
• Sustained VT that does not revert with treatment or requires \>6 hours to be controlled in the 48 hours prior to the product administration procedure
• Complete atrioventricular blockade, or acute left bundle branch block in the 48 hours prior to the product administration procedure
• History of cardioembolic disease
• Platelets \<100,000 and/or Hb\<8.5g/dL
• Acute or chronic renal failure with creatinine ≥2.5 mg/dl or creatinine clearance ≤30 mL/min
• Infection with systemic involvement
• Child-Pugh's C stage chronic liver disease
• Baseline respiratory failure requiring oxygen at home
• Uncontrolled hypertension at screening despite treatment (systolic blood pressure \[BP\] ≥180 and/or diastolic BP ≥110)

Sponsors & Collaborators

• Coretherapix: lead
• European Commission: collaborator
• Universitaire Ziekenhuizen KU Leuven: collaborator
• Saint-Louis Hospital, Paris, France: collaborator
• Hospital General Universitario Gregorio Marañon: collaborator
• Complejo Hospitalario de Navarra: collaborator
• Hospital Clínico Universitario de Valladolid: collaborator
• Hospital Donostia: collaborator
• Hospital Clínico Universitario de Valencia: collaborator
• University of Salamanca: collaborator
• Hospital Universitario Virgen de la Victoria: collaborator

Study Sites (1)

Coretherapix (Tigenix Group)

Tres Cantos, Madrid, 28760, Spain

Location

Related Publications (5)

• Boukouaci W, Lauden L, Siewiera J, Dam N, Hocine HR, Khaznadar Z, Tamouza R, Borlado LR, Charron D, Jabrane-Ferrat N, Al-Daccak R. Natural killer cell crosstalk with allogeneic human cardiac-derived stem/progenitor cells controls persistence. Cardiovasc Res. 2014 Nov 1;104(2):290-302. doi: 10.1093/cvr/cvu208. Epub 2014 Sep 11.

  PMID: 25213554 BACKGROUND

• Lauden L, Boukouaci W, Borlado LR, Lopez IP, Sepulveda P, Tamouza R, Charron D, Al-Daccak R. Allogenicity of human cardiac stem/progenitor cells orchestrated by programmed death ligand 1. Circ Res. 2013 Feb 1;112(3):451-64. doi: 10.1161/CIRCRESAHA.112.276501. Epub 2012 Dec 12.

  PMID: 23243206 BACKGROUND

• Crisostomo V, Baez C, Abad JL, Sanchez B, Alvarez V, Rosado R, Gomez-Mauricio G, Gheysens O, Blanco-Blazquez V, Blazquez R, Toran JL, Casado JG, Aguilar S, Janssens S, Sanchez-Margallo FM, Rodriguez-Borlado L, Bernad A, Palacios I. Dose-dependent improvement of cardiac function in a swine model of acute myocardial infarction after intracoronary administration of allogeneic heart-derived cells. Stem Cell Res Ther. 2019 May 31;10(1):152. doi: 10.1186/s13287-019-1237-6.

  PMID: 31151405 DERIVED

• Fernandez-Aviles F, Sanz-Ruiz R, Bogaert J, Casado Plasencia A, Gilaberte I, Belmans A, Fernandez-Santos ME, Charron D, Mulet M, Yotti R, Palacios I, Luque M, Sadaba R, San Roman JA, Larman M, Sanchez PL, Sanchis J, Jimenez MF, Claus P, Al-Daccak R, Lombardo E, Abad JL, DelaRosa O, Corcostegui L, Bermejo J, Janssens S. Safety and Efficacy of Intracoronary Infusion of Allogeneic Human Cardiac Stem Cells in Patients With ST-Segment Elevation Myocardial Infarction and Left Ventricular Dysfunction. Circ Res. 2018 Aug 17;123(5):579-589. doi: 10.1161/CIRCRESAHA.118.312823.

  PMID: 29921651 DERIVED

• Sanz-Ruiz R, Casado Plasencia A, Borlado LR, Fernandez-Santos ME, Al-Daccak R, Claus P, Palacios I, Sadaba R, Charron D, Bogaert J, Mulet M, Yotti R, Gilaberte I, Bernad A, Bermejo J, Janssens S, Fernandez-Aviles F. Rationale and Design of a Clinical Trial to Evaluate the Safety and Efficacy of Intracoronary Infusion of Allogeneic Human Cardiac Stem Cells in Patients With Acute Myocardial Infarction and Left Ventricular Dysfunction: The Randomized Multicenter Double-Blind Controlled CAREMI Trial (Cardiac Stem Cells in Patients With Acute Myocardial Infarction). Circ Res. 2017 Jun 23;121(1):71-80. doi: 10.1161/CIRCRESAHA.117.310651. Epub 2017 May 22.

  PMID: 28533209 DERIVED

Related Links

• Natural killer cell crosstalk with allogeneic human cardiac-derived stem/progenitor cells controls persistence.
• Allogenicity of human cardiac stem/progenitor cells orchestrated by programmed death ligand
• Sponsor web page
• European Clinical Trial Data Base

Study Officials

• Marie Paule Richard, MD

  Coretherapix (Tigenix Group)

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 27, 2015
• First Posted: May 8, 2015
• Study Start: June 1, 2014
• Primary Completion: December 1, 2015
• Study Completion: November 14, 2016
• Last Updated: November 14, 2017

Record last verified: 2017-11

Locations

ES (1)