Heart FailurePhase 3FLOURISHNCT03360448
AC6 Gene Transfer in Patients With Reduced Left Ventricular Ejection Fraction Heart Failure
A Phase 3 study testing Ad5.hAC6 in people with Heart Failure, run by Renova Therapeutics.
Trial summary
To determine the safety and efficacy of an intracoronary injection of adenovirus 5 encoding human adenylyl cyclase 6 (RT-100) in patients with heart failure with reduced left ventricular ejection fraction (HFrEF) in a Phase 3 clinical trial. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Heart Failure
- What is being tested?
- Ad5.hAC6
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Jun 2019to Jun 2023
- Phase
- Phase 3
- Are there results?
- None posted in the registry
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 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18 to 80 years, inclusive, with history of heart failure (HF).
- Current HF symptoms with NYHA Functional Classification Class II to IV (inclusive) at Screening (Visit 1).
- Currently receiving optimally tolerated standard of care HF medical therapy as defined by the American Heart Association (AHA)/American College of Cardiology (ACC) Heart Failure guidelines and Focused Update along with an angiotensin converting enzyme inhibitor (ACEi)/angiotensin II receptor blockers (ARB), diuretics and sacubitril/valsartan for 4 weeks or longer, without change in drug therapy or dosage regimen, prior to Visit 1 (and continued same HF therapy through Visit 2).
- Left Ventricular Ejection Fraction (LVEF) ≥ 10 to ≤ 35% as determined by Screening echocardiogram (ECHO).
- NT pro BNP ≥ 400 pg/mL.
- If subject has had coronary artery bypass surgery, then at least one conduit must be patent and therefore be amendable for test article.
- Women of child bearing capacity must have a negative pregnancy test before 2 days of test article administration and must not be currently breastfeeding or nursing, and female and male patients must be willing to use birth control for 12 weeks after test article administration if the female partner is of child bearing capacity. Acceptable methods of effective birth control include total sexual abstinence; a condom with spermicide (men) in combination with barrier methods (diaphragm, cervical cap or cervical sponge); hormonal birth control (oral or injectable contraceptives); intrauterine devices; or surgical sterilization (vasectomy and testing that shows there is no sperm in the semen for men and bilateral tubal ligation +/- oophorectomy for women).
- Willing to provide informed consent consistent with International Conference on Harmonisation Good Clinical Practices.
Who cannot join
- Use of intravenous (IV) vasodilatory or inotropic therapy within 24 hours prior to Visit 2.
- Unstable angina within 3 months of Visit 1.
- Coronary revascularization planned or predicted within 6 months prior to Visit 1.
- Subjects who are candidates for revascularization are not considered appropriate for this trial; therefore, if a subject has Ischemia of viable myocardium > 15% and is a candidate for revascularization, this subject would not be eligible to participate in this trial.
- Myocardial infarction within 6 months prior to Screening (Visit 1). Myocardial infarction is defined by documented evidence of a rise and/or fall of cardiac biomarker values (preferably cardiac troponin) with at least one value above the 99th percentile upper reference limit, and either ischemic symptoms, electrocardiogram changes, imaging evidence of loss of viable myocardium or new regional wall motion abnormality, or identification of an intracoronary thrombus by coronary angiography.
- Thrombocytopenia (< 100,000 platelets/µL) or bleeding diathesis.
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- Stroke or transient ischemic attack within 6 months prior to Screening (Visit 1).
- Use of sodium-glucose co-transporter 2 inhibitors used to treat type 2 diabetes mellitus.
- Cardiac:
- Biopsy documenting reversible cause of cardiomyopathy within 6 months of Visit 1 (Screening) if available as part of patient's prior cardiac history.
- Acute cardiac decompensation.
- If coronary angiogram within 6 months, with a presence of untreated severe three vessel coronary disease or unprotected left main coronary artery disease or coronary anatomy unsuitable for study procedure (eg, arterial tortuosity, etc) prior to Randomization (Visit 2).
- Use of IV diuretics within 12 hours of Randomization (Visit 2).
- Hemodynamically significant untreated valvular heart disease based on the AHA/ACC Valvular Heart Disease Guidelines.
- Current evidence of restrictive, peripartum, viral, infectious, infiltrative, or inflammatory cardiomyopathy.
- Significant pericardial effusion at Screening (Visit 1) or at the time of test article administration.
- Current untreated ventricular arrhythmias.
- Currently awaiting planned heart transplantation or ventricular assist device.
- Congenital heart disease (other than small or hemodynamically non significant ventricular septal defect or atrial septal defect).
- Device therapy as noted below:
- Cardiac resynchronization therapy (CRT), or CRT-D/P, is not allowed within 6 months of implantation.
- Implantable Cardioverter Defibrillator or pacemaker implantation is not allowed if implanted < 30 days prior to Screening (Visit 1).
- CardioMems device is not allowed.
- Systolic blood pressure ≥ 160 mm Hg or < 90 mm Hg at Visit 1 or 2.
- Diastolic blood pressure ≥ 95 mm Hg at Visit 1 or 2.
- 6 Minute Walk Test (6MWT):
- Inability to perform the 6MWT for reasons unrelated to heart failure (eg, physical limitations, peripheral vascular disease).
- Distance walked in 6MWT (6MWD) < 100 m
- Pulmonary:
- Pulmonary disease requiring oxygen therapy;
- Severe chronic obstructive pulmonary disease; restrictive lung disease.
- Upper respiratory infection within 4 weeks of Screening (Visit 1).
- History of organ transplant.
- Viral syndrome with fever ≥101° Fahrenheit (patient may be reconsidered for enrollment 4 weeks following resolution of viral syndrome).
- History of human immunodeficiency virus or acquired immunodeficiency syndrome, history of hepatitis C virus, or immunosuppressed by medicines (corticosteroids, methotrexate, cyclophosphamide, cyclosporine).
- Presence of eGFR ≤ 30 mL/min/1.73 m2 using the Cockcroft Gault equation.
- Patients with life expectancy < 1 year.
- Documented Child Pugh B or C hepatic disease.
- Body Mass Index ≥ 40 kg/m2.
- Participation in any other clinical trial or registry within 30 days prior to Randomization (Visit 2).
- Hemoglobin ≤ 10 gm/dL.
- Prior history of malignancy.
- Prior history of gene transfer.
About this study
Official title: Randomized, Phase 3, Placebo-Controlled Double-Blind, Multicenter Trial of a One Time Intracoronary Administration of Ad5.hAC6 Gene Transfer for Patients With Reduced Left Ventricular Heart Failure
To determine the safety and efficacy of an intracoronary injection of adenovirus 5 encoding human adenylyl cyclase 6 (RT-100) in patients with heart failure with reduced left ventricular ejection fraction (HFrEF) in a Phase 3 clinical trial.
Read the detailed description
This is a randomized, placebo-controlled, double-blinded Phase 3 clinical trial using a one-time intracoronary injection of Ad5.hAC6 (or placebo) to determine safety and efficacy in patients with documented HFrEF.
- Conditions
- Heart Failure
- Being tested
- Ad5.hAC6, Placebo
- Keywords
- Gene Transfer
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ad5.hAC6Drug
Also called RT-100
1:1 randomization (Ad5.hAC6 : placebo) - intracoronary delivery
PlaceboDrug
Also called 3% sucrose
1:1 randomization (Ad5.hAC6 : placebo) - intracoronary delivery
| Study group | Role | What they receive |
|---|---|---|
| Experimental | Experimental | Ad5.hAC6: Intracoronary delivery of adenovirus encoding human adenylyl cyclase type 6 Receives: Drug: Ad5.hAC6 |
| Placebo Comparator | Placebo comparator | Placebo: Intracoronary delivery of formulation buffer ( 3% sucrose) Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Heart Failure Hospitalizations
Reduce the event rate of all (first and repeat) heart failure hospitalizations
Measured: Baseline to 12 months
Secondary outcomes (4)
Cardiovascular (CV) Death
Reduce the event rate of cardiovascular (CV) death
Measured: Baseline to 12 months
All Cause Death
Reduce the event rate of death (regardless of cause)
Measured: Baseline to 12 months
New York Heart Association (NYHA) Functional Classification
Improve NYHA functional classification
Measured: Baseline to 12 months
All Heart Failure (HF) Events
Reduce the event rate of all heart failure (HF) events
Measured: Baseline to 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Dec 2017
- Study startJun 2019 (estimated)
- Primary completionJun 2020 (estimated)
- Study completionJun 2023 (estimated)
Why it stopped: Clinical development plans and strategy for RT-100 being re-evaluated
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Heart FailureStudies of the same condition, open and under way.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Renova Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03360448
- Sponsor's protocol ID
- RT-01-HF-REF
- Acronym
- FLOURISH
- Status last verified
- Jun 2019
- First submitted
- 13 Nov 2017
- Last updated
- 7 Jun 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Blinded study - de-identified participant data to become available after completion of study.
Publications
Hammond HK, Penny WF, Traverse JH, Henry TD, Watkins MW, Yancy CW, Sweis RN, Adler ED, Patel AN, Murray DR, Ross RS, Bhargava V, Maisel A, Barnard DD, Lai NC, Dalton ND, Lee ML, Narayan SM, Blanchard DG, Gao MH. Intracoronary Gene Transfer of Adenylyl Cyclase 6 in Patients With Heart Failure: A Randomized Clinical Trial. JAMA Cardiol. 2016 May 1;1(2):163-71. doi: 10.1001/jamacardio.2016.0008.
PubMed 27437887
Study at a glance
From the registry record, last updated by the sponsor on 7 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized, Phase 3, Placebo-Controlled Double-Blind, Multicenter Trial of a One Time Intracoronary Administration of Ad5.hAC6 Gene Transfer for Patients With Reduced Left Ventricular Heart Failure
- ClinicalTrials.gov ID
- NCT03360448
- Acronym / sponsor ID
- FLOURISH / RT-01-HF-REF
- Conditions
- Heart Failure
- Keywords
- Gene Transfer
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Clinical development plans and strategy for RT-100 being re-evaluated
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Renova TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- Jun 2019 (estimated)
- Primary completion
- Jun 2020 (estimated)
- Study completion
- Jun 2023 (estimated)
- First posted
- 4 Dec 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To determine the safety and efficacy of an intracoronary injection of adenovirus 5 encoding human adenylyl cyclase 6 (RT-100) in patients with heart failure with reduced left ventricular ejection fraction (HFrEF) in a Phase 3 clinical trial.
Detailed description
This is a randomized, placebo-controlled, double-blinded Phase 3 clinical trial using a one-time intracoronary injection of Ad5.hAC6 (or placebo) to determine safety and efficacy in patients with documented HFrEF.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Randomized
| Arm | Type | Receives |
|---|---|---|
| Experimental | Experimental | Drug: Ad5.hAC6Ad5.hAC6: Intracoronary delivery of adenovirus encoding human adenylyl cyclase type 6 |
| Placebo Comparator | Placebo comparator | Drug: PlaceboPlacebo: Intracoronary delivery of formulation buffer ( 3% sucrose) |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Age 18 to 80 years, inclusive, with history of heart failure (HF).
- Current HF symptoms with NYHA Functional Classification Class II to IV (inclusive) at Screening (Visit 1).
- Currently receiving optimally tolerated standard of care HF medical therapy as defined by the American Heart Association (AHA)/American College of Cardiology (ACC) Heart Failure guidelines and Focused Update along with an angiotensin converting enzyme inhibitor (ACEi)/angiotensin II receptor blockers (ARB), diuretics and sacubitril/valsartan for 4 weeks or longer, without change in drug therapy or dosage regimen, prior to Visit 1 (and continued same HF therapy through Visit 2).
- Left Ventricular Ejection Fraction (LVEF) ≥ 10 to ≤ 35% as determined by Screening echocardiogram (ECHO).
- NT pro BNP ≥ 400 pg/mL.
Key exclusion criteria (43 listed)
- Use of intravenous (IV) vasodilatory or inotropic therapy within 24 hours prior to Visit 2.
- Unstable angina within 3 months of Visit 1.
- Coronary revascularization planned or predicted within 6 months prior to Visit 1.
- Subjects who are candidates for revascularization are not considered appropriate for this trial; therefore, if a subject has Ischemia of viable myocardium > 15% and is a candidate for revascularization, this subject would not be eligible to participate in this trial.
- Myocardial infarction within 6 months prior to Screening (Visit 1). Myocardial infarction is defined by documented evidence of a rise and/or fall of cardiac biomarker values (preferably cardiac troponin) with at least one value above the 99th percentile upper reference limit, and either ischemic symptoms, electrocardiogram changes, imaging evidence of loss of viable myocardium or new regional wall motion abnormality, or identification of an intracoronary thrombus by coronary angiography.
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 |
|---|---|---|
| Ad5.hAC6Also: RT-1001:1 randomization (Ad5.hAC6 : placebo) - intracoronary delivery | Drug | Experimental |
| PlaceboAlso: 3% sucrose1:1 randomization (Ad5.hAC6 : placebo) - intracoronary delivery | Drug | Placebo Comparator |
Primary outcome
Heart Failure Hospitalizations
Time frame: Baseline to 12 months
Reduce the event rate of all (first and repeat) heart failure hospitalizations
4 secondary outcomes
Cardiovascular (CV) Death
Time frame: Baseline to 12 months
All Cause Death
Time frame: Baseline to 12 months
New York Heart Association (NYHA) Functional Classification
Time frame: Baseline to 12 months
All Heart Failure (HF) Events
Time frame: Baseline to 12 months
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jun 2019.
- Background: PubMed 27437887Hammond HK, Penny WF, Traverse JH, Henry TD, Watkins MW, Yancy CW, Sweis RN, Adler ED, Patel AN, Murray DR, Ross RS, Bhargava V, Maisel A, Barnard DD, Lai NC, Dalton ND, Lee ML, Narayan SM, Blanchard DG, Gao MH. Intracoronary Gene Transfer of Adenylyl Cyclase 6 in Patients With Heart Failure: A Randomized Clinical Trial. JAMA Cardiol. 2016 May 1;1(2):163-71. doi: 10.1001/jamacardio.2016.0008.
- Individual participant dataSharing planned: Undecided. Blinded study - de-identified participant data to become available after completion of study.
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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.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Ad5.hAC6 in people with Heart Failure, run by Renova Therapeutics.
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 8 inclusion and 43 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: withdrawn, as of the sponsor's last update on 7 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.
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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
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?
Heart Failure Hospitalizations (time frame: Baseline to 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03360448, which also lists 1 linked publication.
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 7 Jun 2019.