Regression of Fibrosis & Reversal of Diastolic Dysfunction in HFpEF Patients Treated With Allogeneic CDCs

NCT02941705 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 54823
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

Perform a randomized, double blind, placebo-controlled Phase 2a feasibility study to determine whether treatment of HFpEF patients with intracoronary allogeneic CDCs affects clinical functional status (QOL scores), exercise tolerance (6MHW), exercise hemodynamics (supine exercise ergometry during right heart catheterization), myocardial interstitial fibrosis (MRI with native T1 mapping and calculation of extracellular volume \[ECV\] after gadolinium administration), macroscopic fibrosis by delayed gadolinium enhancement (DGE), and diastolic function (catheterization, echocardiography, BNP). Treatment of patients with symptomatic hypertensive heart disease-induced HFpEF with allogeneic CDCs will be safe and will improve clinical functional status, exercise tolerance/hemodynamics, myocardial interstitial structure, and diastolic function; the mechanisms underlying these improvements will be reflected in changes in plasma biomarkers that indicate a reduction in pro-inflammatory and pro-fibrotic signaling.

Conditions

Congestive Heart Failure; Heart Failure, Diastolic

Keywords

stem cell research

Outcome Measures

Primary Outcomes (1)

• the Safety Profile of CAP 1002; Any Subjects Experiencing Any Safety Related Events During or Post Intracoronary Delivery and During the Follow up Period.

  any subjects experiencing any safety related events during or post intracoronary delivery and during the follow up period. Safety outcomes will be measured through TIMI flow 0-2, acute myocarditis within one month of intracoronary infusion, ventricular tachycardia or ventricular fibrillation within 72 hours of intracoronary infusion, sudden unexpected death within 72 hours of intracoronary infusion defined as occurring 1 hour within in symptom onset or witnessed death in a subject previously observed to be well within the preceding 24 hours without an identified cause, or a major adverse cardiac event within 72 hours of intracoronary infusion.

  one year

Study Arms (2)

RECIEVED CELLS

ACTIVE COMPARATOR

this arm will receive the CDCs /CAP 1002 solution

Biological: Allogeneic Derived Cells

CONTROL ARM

PLACEBO COMPARATOR

this arm will receive a solution during randomization but will not receive the CDCs

Biological: Placebo/Control Arm

Interventions

Allogeneic Derived Cells BIOLOGICAL

patients will have the CAP-1002 solution delivered through a coronary catheter inserted in the right and left coronary arteries using standard techniques in the cardiac catheterization laboratory. A right heart catheter will be used to obtain baseline (pre-infusion) hemodynamics.

Also known as: CAP-1002

RECIEVED CELLS

Placebo/Control Arm BIOLOGICAL

patients will receive the placebo through a coronary catheter inserted in the right and left coronary arteries using standard techniques in the cardiac catheterization laboratory. A right heart catheter will be used to obtain baseline (pre-infusion) hemodynamics.

Also known as: Placebo

CONTROL ARM

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥ 50 years old, male or female
• LVEF ≥ 50%
• Symptoms and physical findings of chronic heart failure (NYHA class II- ambulatory IV)
• Treatment with a stable, maximally-tolerated dose of diuretic(s) for a minimum of 30 days prior to randomization.
• Left atrial (LA) enlargement defined by at least one of the following: LA width (diameter) ≥ 3.8 cm or LA length ≥ 5.0 cm or LA area ≥ 20 cm2 or LA volume ≥ 55 mL or LA volume index ≥ 29 mL/m2
• BNP \> 125 pg/ml for patients in NSR or \> 150 pg/ml for patients in AF (BNP are BMI corrected) or resting PCWP \> 15 mmHg, or exercise PCWP \> 18 mmHg

You may not qualify if:

• Any prior echocardiographic measurement of LVEF \< 40 %
• Acute coronary syndrome (including MI), cardiac surgery, other major CV surgery, or percutaneous coronary intervention (PCI) within the 3 months prior to randomization
• Unrevascularized, hemodynamically significant CAD (FFR \< 0.75)
• Current acute decompensated HF
• Alternative diagnoses that in the opinion of the investigator could account for the patient's HF symptoms (i.e., dyspnea, fatigue) such as severe pulmonary disease (i.e., requiring home oxygen, chronic nebulizer therapy, chronic oral steroid therapy); hemoglobin (Hgb) \< 10 g/dl; body mass index (BMI) \> 40 kg/m2
• Use of investigational drugs or treatments at the time of enrollment
• Systolic blood pressure \> 150 mmHg but \< 180 mmHg unless receiving 3 or more antihypertensive drugs
• History of any dilated cardiomyopathy; right sided HF in the absence of left-sided structural heart disease; Pericardial constriction, genetic hypertrophic cardiomyopathy, or infiltrative cardiomyopathy; clinically significant congenital heart disease; hemodynamically significant valvular heart disease
• Stroke, transient ischemic attack, carotid surgery or carotid angioplasty within the 3 months
• Uncontrolled dysrhythmia; symptomatic or sustained ventricular tachycardia or atrial fibrillation or flutter with a resting ventricular rate \> 110 beats per minute (bpm)
• Prior major organ transplant or intent to transplant (i.e., on transplant list)
• Hepatic disease as determined by any one of the following: SGOT (AST) or SGPT (ALT) values exceeding 3x the upper limit of normal (ULN), bilirubin \> 1.5 mg/dl; history of chronic viral hepatitis
• Chronic Kidney Disease with eGFR \< 30 mL/min/1.73 m2; serum potassium \> 5.5 mmol/L (mEq/L)
• History or presence of any other disease with a life expectancy of \< 3 years
• Non-compliance to medical regimens

Sponsors & Collaborators

• Cedars-Sinai Medical Center: lead
• Medical University of South Carolina: collaborator

Study Sites (1)

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

MeSH Terms

Conditions

Heart Failure; Heart Failure, Diastolic

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Results Point of Contact

• Title: Russell Haber
• Organization: Cedar Sinai

Russell.Haber@CSHS.org

(310) 967-8322

Study Officials

• Michael Zile, MD

  Medical University of South Carolina

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Heart Institute

Study Record Dates

• First Submitted: August 10, 2016
• First Posted: October 21, 2016
• Study Start: July 12, 2017
• Primary Completion: April 28, 2023
• Study Completion: May 31, 2023
• Last Updated: July 25, 2024
• Results First Posted: July 25, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)