Trial Outcomes & Findings for Investigation of the Safety and Feasibility of AAV1/SERCA2a Gene Transfer in Patients With Chronic Heart Failure (NCT NCT00534703)

NCT ID: NCT00534703

Last Updated: 2023-02-08

Results Overview

Safety is defined as the incidence of patients experiencing death and major adverse cardiovascular events, and out of range laboratory values. Both AAV1/SERCA2a treated cohorts (NAb+ and NAb-) will be compared to the placebo group.

• Recruitment status: TERMINATED
• Study phase: PHASE2
• Target enrollment: 5 participants
• Primary outcome timeframe: 6 months
• Results posted on: 2023-02-08

Participant Flow

Participant milestones

Measure	AAV1/SERCA2A SERCA gene therapy AAV1/SERCA2a: 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) 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.
Overall Study STARTED	4	1
Overall Study COMPLETED	4	1
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	AAV1/SERCA2A n=4 Participants SERCA gene therapy AAV1/SERCA2a: AAV1/SERCA2a will be delivered by a percutaneous method in the catheter laboratory. Dose: 1x 10\^13 DRP (DNase resistant particles)	Placebo n=1 Participants Placebo (saline solution) 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.	Total n=5 Participants Total of all reporting groups
Age, Continuous	41 years n=5 Participants	49 years n=7 Participants	42.6 years n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Race/Ethnicity, Customized White	4 Participants n=5 Participants	0 Participants n=7 Participants	4 Participants n=5 Participants
Race/Ethnicity, Customized Black	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: 6 months

Population: The trial was terminated early with only 5 subjects enrolled. As a result full statistical analysis for both primary and secondary outcomes was impossible and results have been presented taking a descriptive approach instead

Safety is defined as the incidence of patients experiencing death and major adverse cardiovascular events, and out of range laboratory values. Both AAV1/SERCA2a treated cohorts (NAb+ and NAb-) will be compared to the placebo group.

Outcome measures

Measure	AAV1/SERCA2A n=4 Participants SERCA gene therapy AAV1/SERCA2a: AAV1/SERCA2a will be delivered by a percutaneous method in the catheter laboratory. Dose: 1x 10\^13 DRP (DNase resistant particles) No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The trial was terminated early with only 5 subjects enrolled. As a result full statistical analysis for both primary and secondary outcomes was impossible and a more pragmatic approach was undertaken to assess product safety.	Placebo n=1 Participants Placebo (saline solution) 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. No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The trial was terminated early with only 5 subjects enrolled. As a result full statistical analysis for both primary and secondary outcomes was impossible and a more pragmatic approach was undertaken to assess product safety.
Overall Safety and Feasibility of Administering AAV1/SERCA2a to LVAD Patients	NA Participants The trial was terminated early with only 5 subjects enrolled. As a result full statistical analysis for both primary and secondary outcomes was impossible and a more pragmatic approach was undertaken to assess product safety.	NA Participants The trial was terminated early with only 5 subjects enrolled. As a result full statistical analysis for both primary and secondary outcomes was impossible and a more pragmatic approach was undertaken to assess product safety.

SECONDARY outcome

Timeframe: 6 months

The trial was terminated early with only 5 subjects enrolled. As a result full statistical analysis for both primary and secondary outcomes was impossible and a more pragmatic approach was undertaken to assess product safety.

Outcome measures

Measure	AAV1/SERCA2A n=4 Participants SERCA gene therapy AAV1/SERCA2a: AAV1/SERCA2a will be delivered by a percutaneous method in the catheter laboratory. Dose: 1x 10\^13 DRP (DNase resistant particles) No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The trial was terminated early with only 5 subjects enrolled. As a result full statistical analysis for both primary and secondary outcomes was impossible and a more pragmatic approach was undertaken to assess product safety.	Placebo n=1 Participants Placebo (saline solution) 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. No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The trial was terminated early with only 5 subjects enrolled. As a result full statistical analysis for both primary and secondary outcomes was impossible and a more pragmatic approach was undertaken to assess product safety.
Number of Participants With Exogenous Viral Vector Genome in the Myocardium Measured by qPCR for the Viral DNA	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 6 months

Population: Note: The trial was terminated early with only 5 subjects enrolled. As a result, full statistical analysis for both primary and secondary outcomes was impossible and results have been presented using a descriptive approach

Left ventricular function assessed by echocardiography and exercise capacity (6MWT, MVO2) during minimal LVAD support (low/no flow settings depending upon device) LVEF expressed as %

Outcome measures

Measure	AAV1/SERCA2A n=4 Participants SERCA gene therapy AAV1/SERCA2a: AAV1/SERCA2a will be delivered by a percutaneous method in the catheter laboratory. Dose: 1x 10\^13 DRP (DNase resistant particles) No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The trial was terminated early with only 5 subjects enrolled. As a result full statistical analysis for both primary and secondary outcomes was impossible and a more pragmatic approach was undertaken to assess product safety.	Placebo n=1 Participants Placebo (saline solution) 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. No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The trial was terminated early with only 5 subjects enrolled. As a result full statistical analysis for both primary and secondary outcomes was impossible and a more pragmatic approach was undertaken to assess product safety.
Left Ventricular Function (LVEF)	NA Participants Note: The trial was terminated early with only 5 subjects enrolled. As a result, full statistical analysis for both primary and secondary outcomes was impossible and a more pragmatic approach was undertaken to assess product safety.	NA Participants Note: The trial was terminated early with only 5 subjects enrolled. As a result, full statistical analysis for both primary and secondary outcomes was impossible and a more pragmatic approach was undertaken to assess product safety.

SECONDARY outcome

Timeframe: 6 months

Population: Data not collected due to early termination of the trial

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 6 months

Population: Data not collected due to early termination of the trial

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 6 months

Population: Data not collected due to early termination of the trial

Outcome measures

Outcome data not reported

Adverse Events

AAV1/SERCA2A

Serious events: 2 serious events

Other events: 4 other events

Deaths: 1 deaths

Placebo

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Measure	AAV1/SERCA2A n=4 participants at risk SERCA gene therapy AAV1/SERCA2a: AAV1/SERCA2a will be delivered by a percutaneous method in the catheter laboratory. Dose: 1x 10\^13 DRP (DNase resistant particles)	Placebo n=1 participants at risk Placebo (saline solution) 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.
Product Issues LVAD Alarm	25.0% 1/4 • Number of events 1 • 6 Months	0.00% 0/1 • 6 Months
Cardiac disorders Worsening heart failure	25.0% 1/4 • Number of events 1 • 6 Months	0.00% 0/1 • 6 Months
Surgical and medical procedures Heart transplantation	25.0% 1/4 • Number of events 1 • 6 Months	0.00% 0/1 • 6 Months
General disorders Death	25.0% 1/4 • Number of events 1 • 6 Months	0.00% 0/1 • 6 Months

Other adverse events

Measure	AAV1/SERCA2A n=4 participants at risk SERCA gene therapy AAV1/SERCA2a: AAV1/SERCA2a will be delivered by a percutaneous method in the catheter laboratory. Dose: 1x 10\^13 DRP (DNase resistant particles)	Placebo n=1 participants at risk Placebo (saline solution) 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.
Injury, poisoning and procedural complications Vessel puncture, site haematoma	25.0% 1/4 • Number of events 1 • 6 Months	0.00% 0/1 • 6 Months
Cardiac disorders Myocarditis	0.00% 0/4 • 6 Months	100.0% 1/1 • Number of events 1 • 6 Months
Cardiac disorders Atrial Flutter	0.00% 0/4 • 6 Months	100.0% 1/1 • Number of events 1 • 6 Months
Blood and lymphatic system disorders Iron deficiency - Anaemia	25.0% 1/4 • Number of events 1 • 6 Months	0.00% 0/1 • 6 Months
Respiratory, thoracic and mediastinal disorders Rhinitis	25.0% 1/4 • Number of events 1 • 6 Months	0.00% 0/1 • 6 Months
General disorders Site Bleeding	25.0% 1/4 • Number of events 1 • 6 Months	0.00% 0/1 • 6 Months
General disorders Malaise	25.0% 1/4 • Number of events 1 • 6 Months	0.00% 0/1 • 6 Months
Skin and subcutaneous tissue disorders Skin Lesion	25.0% 1/4 • Number of events 1 • 6 Months	0.00% 0/1 • 6 Months
Product Issues Device Alarm Issue	25.0% 1/4 • Number of events 1 • 6 Months	0.00% 0/1 • 6 Months
Metabolism and nutrition disorders Hyperkalaemia	25.0% 1/4 • Number of events 1 • 6 Months	0.00% 0/1 • 6 Months
Infections and infestations Device related infection	50.0% 2/4 • Number of events 2 • 6 Months	0.00% 0/1 • 6 Months

Additional Information

Dr Alexander Lyon

Imperial College London

Phone: +442075943409

Email: a.lyon@imperial.ac.uk

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place