Investigation of the Safety and Feasibility of AAV1/SERCA2a Gene Transfer in Patients With Chronic Heart Failure

NCT ID: NCT00534703

Last Updated: 2023-02-08

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 5 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-07-31
• Study Completion Date: 2015-09-30

Brief Summary

The aim of the study is to determine the safety and feasibility of giving an adeno-associated viral vector expressing the sarcoplasmic reticulum calcium ATPase (SERCA2a), driven by the CMV promoter (AAV1-CMV-SERCA2a), to heart failure patients that have received a left ventricular assist device (LVAD) for an accepted clinical indication.

Detailed Description

It is a randomised, double-blind study of 24 patients that will be randomised to receive either the study drug (AAV1.SERCA2a) or placebo.

The purpose of gene transfer of SERCA2a is to improve systolic and diastolic function of the failing ventricle. Studies show that reduction of SERCA2a in failing ventricle is a key factor in depression of contraction, and that restoration of SERCA2a levels can improve function to near normal levels. The vector will be delivered during a cardiac catheterisation procedure by a 10-minute infusion into the coronary arteries.

Myocardial tissue is obtained at the time of LVAD placement, as a routine part of device implantation. Further samples will be obtained when the heart is transplanted or the LVAD removed. Measures of tissue inflammation as well as efficacy of gene transfer will be made by comparing these two samples. Recovery of contractile function of the heart will be assessed during attempts to wean patients from the LVAD using standard protocols.

The results will be assessed in conjunction with two companion studies which will start earlier in the US, one performing SERCA2a gene transfer with the same vector, but delivered by direct injection into the myocardium during LVAD insertion, and one using AAV1-CMV-SERCA2a delivered percutaneously in heart failure patients. The latter has both a dose-ranging and placebo-controlled arm.

Conditions

Chronic Heart Failure; Patients That Have Received a Left Ventricular Assist Device

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

AAV1/SERCA2A

SERCA gene therapy

Group Type: ACTIVE_COMPARATOR

AAV1/SERCA2a

Intervention Type: GENETIC

AAV1/SERCA2a will be delivered by a percutaneous method in the catheter laboratory. Dose: 1x 10\^13 DRP (DNase resistant particles)

Placebo

Placebo (saline solution)

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo aliquots will be of the same composition as the investigational medicinal product with the absence of the active ingredient and will be visually indistinguishable from the medicinal product. Placebo is prepared and handled exactly as above in a blinded fashion.

Interventions

AAV1/SERCA2a

AAV1/SERCA2a will be delivered by a percutaneous method in the catheter laboratory. Dose: 1x 10\^13 DRP (DNase resistant particles)

Intervention Type: GENETIC

Placebo

Placebo aliquots will be of the same composition as the investigational medicinal product with the absence of the active ingredient and will be visually indistinguishable from the medicinal product. Placebo is prepared and handled exactly as above in a blinded fashion.

Intervention Type: DRUG

Other Intervention Names

MYDICAR (R)

Eligibility Criteria

Inclusion Criteria

• Patients that have had a left ventricular assist device (LVAD) implanted for chronic heart failure, where chronic heart failure is defined as at least 6 months
• Patients are clinically stable in the opinion of the clinical team looking after the patient
• Written informed consent

Exclusion Criteria

• <18 or >70 years of age at the time of consent
• Pregnancy or within 6 months of giving birth
• Women of child-bearing potential not using an effective method of contraception
• Men not using an effective method of contraception
• Suspected or active viral, fungal or parasitic infection within 48 hours prior to administration of IMP, in the opinion of the investigator*.
• Patients at a high risk of thrombosis in the opinion of the investigator
• Patients with a previous episode of LVAD thrombosis
• Patients with persistently raised lactate dehydrogenase (LDH >2.5 ULN)
• Patients requiring triple anticoagulation i.e. warfarin and dual anti-platelet
• Patients participating in another clinical trial
• Patients unable to comply with the protocol mandated procedures for social or other reasons, in the opinion of the investigator and primary care physician

• Eligible, enrolled and randomised patients who develop an infection will have study treatment delayed until 7 or more days after the time point when infection is no longer clinically evident.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

British Heart Foundation

OTHER

Sponsor Role: collaborator

Leducq Foundation

OTHER

Sponsor Role: collaborator

Celladon Corporation

INDUSTRY

Sponsor Role: collaborator

Imperial College London

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sian Harding

Role: PRINCIPAL_INVESTIGATOR

Imperial College London

Alexander Lyon

Role: PRINCIPAL_INVESTIGATOR

Imperial College London

Locations

Papworth Hospital

Cambridge, , United Kingdom

Harefield Hospital, Royal Brompton and Harefiled NHS Trust

Middlesex, , United Kingdom

Countries

United Kingdom

Other Identifiers

2007-002809-48

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CRO782

Identifier Type: -

Identifier Source: org_study_id