Chronic Heart FailurePhase 2SERCA-LVADNCT00534703
Investigation of the Safety and Feasibility of AAV1/SERCA2a Gene Transfer in Patients With Chronic Heart Failure
A Phase 2 study testing AAV1/SERCA2a in people with Chronic Heart Failure and Patients That Have Received a Left Ventricular Assist Device, run by Imperial College London at 2 sites in United Kingdom.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Chronic Heart Failure, Patients That Have Received a Left Ventricular Assist Device
- What is being tested?
- AAV1/SERCA2a
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 5 participants
- Where
- 2 sitesUnited Kingdom
- Study dates
- Jul 2014to Sep 2015
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- <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
Show all 12Show fewer
- 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.
Trial locations and contacts
2 sites in 1 country.
United Kingdom2 sites
Papworth Hospital
Cambridge, CB23 3RE
Harefield Hospital, Royal Brompton and Harefiled NHS Trust
Middlesex, UB9 6JH
About this study
Official title: Investigation of the Safety and Feasibility of AAV1/SERCA2a Gene Transfer in Patients With Chronic Heart Failure and a Left Ventricular Assist Device
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.
Read the 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.
- Being tested
- AAV1/SERCA2a, Placebo
- Keywords
- Chronic Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AAV1/SERCA2aGenetic
Also called MYDICAR (R)
AAV1/SERCA2a will be delivered by a percutaneous method in the catheter laboratory. Dose: 1x 10^13 DRP (DNase resistant particles)
PlaceboDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| AAV1/SERCA2A | Active comparator | SERCA gene therapy Receives: Genetic: AAV1/SERCA2a |
| Placebo | Placebo comparator | Placebo (saline solution) Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Safety and Feasibility of Administering AAV1/SERCA2a to LVAD Patients
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.
Measured: 6 months
Secondary outcomes (5)
Number of Participants With Exogenous Viral Vector Genome in the Myocardium Measured by qPCR for the Viral DNA
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.
Measured: 6 months
Left Ventricular Function (LVEF)
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 %
Measured: 6 months
Levels of SERCA2a Protein
Measured: 6 months
Other Relevant Proteins e.g. Phospholamban, the Sarcoplasmic Reticulum Calcium Release Channel, the Na+/Ca2+-Exchanger.
Measured: 6 months
Function of Isolated Myocytes
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Sep 2007 (estimated)
- Study startJul 2014
- Primary completionSep 2015
- Study completionSep 2015
Why it stopped: Early termination following Trial Steering Committee recommendation
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Chronic Heart FailureStudies of the same condition, open and under way.
- More trials run by Imperial College LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Imperial College London
- Sponsor type
- University, hospital or other
- Collaborators
- British Heart Foundation, Leducq Foundation, Celladon Corporation
- Responsible party
- Sponsor
- Investigators
- Sian Harding, Principal investigator, Imperial College LondonAlexander Lyon, Principal investigator, Imperial College London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00534703
- Sponsor's protocol ID
- CRO782
- Other IDs
- 2007-002809-48
- Acronym
- SERCA-LVAD
- Status last verified
- Jan 2023
- First submitted
- 24 Sep 2007
- Last updated
- 8 Feb 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Investigation of the Safety and Feasibility of AAV1/SERCA2a Gene Transfer in Patients With Chronic Heart Failure and a Left Ventricular Assist Device
- ClinicalTrials.gov ID
- NCT00534703
- Acronym / sponsor ID
- SERCA-LVAD / CRO782
- Keywords
- Chronic Heart Failure
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Early termination following Trial Steering Committee recommendation
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Imperial College LondonUniversity, hospital or other
- Collaborators
- British Heart Foundation, Leducq Foundation, Celladon Corporation
- Study start
- Jul 2014 (actual)
- Primary completion
- Sep 2015 (actual)
- Study completion
- Sep 2015 (actual)
- First posted
- 26 Sep 2007 (estimated)
- Results
- Posted 25 Feb 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| AAV1/SERCA2A | Active comparator | Genetic: AAV1/SERCA2aSERCA gene therapy |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo (saline solution) |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (12 listed)
- <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*.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AAV1/SERCA2aAlso: MYDICAR (R)AAV1/SERCA2a will be delivered by a percutaneous method in the catheter laboratory. Dose: 1x 10^13 DRP (DNase resistant particles) | Genetic | AAV1/SERCA2A |
| PlaceboPlacebo 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. | Drug | Placebo |
Primary outcome
Overall Safety and Feasibility of Administering AAV1/SERCA2a to LVAD Patients
Time frame: 6 months
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.
5 secondary outcomes
Number of Participants With Exogenous Viral Vector Genome in the Myocardium Measured by qPCR for the Viral DNA
Time frame: 6 months
Left Ventricular Function (LVEF)
Time frame: 6 months
Levels of SERCA2a Protein
Time frame: 6 months
Other Relevant Proteins e.g. Phospholamban, the Sarcoplasmic Reticulum Calcium Release Channel, the Na+/Ca2+-Exchanger.
Time frame: 6 months
Function of Isolated Myocytes
Time frame: 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Feb 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sian Harding principal investigator
Imperial College London
Alexander Lyon principal investigator
Imperial College London
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing AAV1/SERCA2a in people with Chronic Heart Failure and Patients That Have Received a Left Ventricular Assist Device, run by Imperial College London at 2 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 8 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Feb 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Safety and Feasibility of Administering AAV1/SERCA2a to LVAD Patients (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Feb 2023.