GenePHIT: A study to learn more about how well a new gene therapy (AB-1002) works and its safety in participants with congestive heart failure

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Askbio Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

5 Nov 2024 → ongoing

Decision date (initial)

2024-09-15

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

AskBio Inc.

External identifiers

EU CT number

2024-510581-17-00

ClinicalTrials.gov

NCT05598333

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

evaluate the efficacy and safety of a single antegrade intracoronary artery infusion of AB-1002 compared to placebo infusion in subjects with non-ischemic cardiomyopathy and NYHA Class III symptoms of HF

Secondary objectives 1

1. To evaluate the impact of AB-1002 on cardiac function, exercise capacity, quality of life (QOL), and the cardiac biomarkers, N-terminal pro-hormone b-type natriuretic peptide (NT-proBNP) levels.

Conditions and MedDRA coding

Adult subjects with New York Heart Association (NYHA) Class III congestive heart failure and non-ischemic cardiomyopathy

Regulatory references

Scientific advice from competent authorities

Medicines Evaluation Board, Austrian Federal Office For Safety In Health Care

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Subject must be age ≥18 years of age, at the time of signing the informed consent
2. Chronic non-ischemic cardiomyopathy
3. 15% ≤ LVEF ≤ 35% by transthoracic echocardiography (TTE) at screening
4. 6MWT >50 meters
5. Medically stable, NYHA Class III HF for a minimum of 4 weeks while on appropriate medical therapy (defined below) including, but not limited to: a. Angiotensin-converting enzyme inhibitor (ACE-I), angiotensin receptor-neprilysin inhibitor (ARNI), angiotensin receptor blocker (ARB), sacubitril/valsartan combination therapy (Entresto), beta blocker therapy, mineralocorticoid receptor antagonist (MRA), sodium-glucose co-transporter 2 inhibitor (SGLT2i) for ≥ 90 days prior to enrollment. Doses of the above medications must be stable for ≥ 30 days prior to enrollment. b. Cardiac resynchronization therapy (Zareba et al., 2011), if clinically indicated, must have been implanted ≥ 90 days prior to enrollment. ICD must be implanted, if clinically indicated ≥ 30 days prior to enrollment.
6. Women of childbearing potentia (for definition see also Section 9.4.1)l must use at least one of the following highly effective birth control methods throughout the study: - Intrauterine device in place at least 90 days prior receiving SI - Abstinence (the subject must be willing to remain abstinent from screening to 6 months after receiving SI). Females are allowed to claim abstinence as their method of contraception only when it is the preferred and usual lifestyle of the subject - Surgical sterilization of the partner(s) (vasectomy) for >180 days prior to SI administration - Hormonal contraceptives associated with the inhibition of ovulation starting > 90 days prior to SI. If hormonal contraceptives are started less than 90 days prior to receiving SI, subjects must agree to use a barrier method (diaphragm plus spermicide or condom) from screening through 90 days after initiation of hormonal contraceptives
7. Males subjects capable of fathering a child: - Must agree not to donate sperm for 6 months (in Belgium: 12 months) after time of receiving SI - Documented evidence of vasectomy in males for 180 days minimum prior to receiving SI is an acceptable form of contraception - Males who claim abstinence as their method of contraception are allowed, provided they agree to use barrier methods should they become sexually active from screening through 6 months (in Belgium: 12 months) after receiving IP. Males are allowed to claim abstinence as their method of contraception only when it is the preferred and usual lifestyle of the subject
8. Appropriate candidate for protocol-specified intracoronary infusion in the judgment of the infusing interventional cardiologist
9. To protect partners of study subjects from potential viral shedding, sexually active subjects and their partners must agree to use barrier methods of contraception (condoms, female condoms, and dams) for a minimum of 6 months (in Belgium: 12 months) after SI administration; barrier methods should be used regardless of any other applied birth control methods.

Exclusion criteria 25

1. Chronic ischemic cardiomyopathy secondary to obstructive coronary artery disease
2. Intravenous (IV) inotropic therapy, intra-aortic balloon pump (IABP) or percutaneous cardiac assist device therapy within 30 days prior to enrollment
3. Restrictive cardiomyopathy, obstructive cardiomyopathy, pericardial disease, amyloidosis, infiltrative cardiomyopathy, uncorrected thyroid disease, or dyskinetic LV aneurysm
4. Cardiac surgery or PCI within 30 days prior to enrollment
5. Uncorrected third degree heart block
6. Clinically significant MI in the judgment of the subject’s physician (e.g., ST elevation MI [STEMI] or large non-STEMI) within 6 months prior to enrollment
7. Prior heart transplantation, left ventricular reduction surgery (LVRS), cardiomyoplasty, passive restraint device (e.g., CorCap™ Cardiac Support Device), surgically implanted LVAD or cardiac shunt
8. Likely to receive cardiac resynchronization therapy, cardiomyoplasty, LV reduction surgery, heart transplant, conventional revascularization procedure, or valvular repair within 3 months of SI dosing in the judgment of the investigator
9. Known hypersensitivity to contrast dyes (not easily controlled by antihistamines) used for angiography; history of, or likely need for, high dose steroid pretreatment prior to contrast angiography
10. known hypersensivity to SI or to any of the exipients or to the placebo
11. Expected survival < 1 year in the judgment of the investigator
12. Clinicially relevant infection 48 hours prior to intracoronary infusion
13. Known intrinsic liver disease (e.g., cirrhosis, hepatitis A, chronic hepatitis B or hepatitis C virus infection). If serology is positive and polymerase chain reaction (PCR) is known to be negative, the subject may be eligible (confirm with medical monitor)
14. Liver function tests (alanine aminotransferase [ALT], aspartate aminotransferase [AST], alkaline phosphatase or total bilirubin) > 2x upper limit of normal (ULN) within 30 days prior to enrollment. In the case that patients have a confirmed diagnosis of benign liver dysfunction (e.g. Gilbert’s syndrome with unconjugated bilirubin not exceeding 4 mg/dL), patients may be eligible for inclusion into the study).
15. Chronic Kidney Disease Stage 5, dialysis dependent or eGFR<15 within 30 days prior to enrollment
16. Bleeding diathesis or thrombocytopenia defined as platelets <50,000 platelets/μL within 30 days prior to enrollment
17. Anemia is defined as hemoglobin <10 g/dL or transfusion dependent within 30 days prior to enrollment
18. Neutropenia is defined as absolute neutrophils <1500 mm3 within 30 days prior to enrollment
19. Known AIDS or HIV-positive status, or a previous diagnosis of immunodeficiency with an absolute neutrophil count <1000 cells/mm3
20. Previous participation in a study of gene transfer
21. Receiving investigational intervention or participating in another clinical study within 30 days of another investigational drug administration prior to administration of AB-1002 that may impact the therapeutic potential of AB-1002
22. Pregnancy or breastfeeding or plans to become pregnant within the next 12 months at the time of screening
23. Subjects with any other condition which in the opinion of the investigator would preclude participation in the study (including risk for noncompliance and any intercurrent conditions that pose an undue medical hazard, or which could interfere with the interpretation of the study results)
24. Malignant neoplasm within 5 years of dosing, with the exception of those with negligible risk of metastasis or death (such as adequately treated carcinoma in situs of the cervix, basal or squamous cell skin cancer, localized prostate cancer or ductal carcinoma in situ)
25. Any documented history of noncompliance with medications; illicit drug use or laboratory evidence of illicit drug use during screen period

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Modified Win Ratio at 52-weeks as defined by hierarchical evaluation of the following assessments in the given order: - Cardiovascular related death (Binary) - NYHA Classification change from baseline (Ordinal) - LVEF change from baseline (Binary, >=5% increase for responders) - six-minute walk test (6MWT) change from baseline (Binary >30m increase for responders)
2. The safety endpoints will be assessed over the 52-week Observation Period as indicated in the Schedule of Activities: - Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) - Observed value and change from baseline in clinical laboratory tests - Observed value and change from baseline in vital signs - Observed value and change from baseline in electrocardiograms (ECGs)

Secondary endpoints 11

1. Cardiovascular related death
2. Functional Status and Hospitalizations at 24 and 52 weeks
3. Observed value and change from baseline in NYHA Classification
4. Observed value and change from baseline in LVEF
5. Observed value and change from baseline in 6MWT
6. Number of HF hospitalizations
7. Time to first HF hospitalization
8. Physiologic Assessments
9. Observed value and change from baseline in Echocardiographic assessments of: - LVEF (at 4, 12 and 36 weeks) - LV volumes: end systolic and end diastolic volumes - LVEDV and left ventricular end diastolic index (LVEDVI) - LVESV and LVESVI - sphericity index (SpI) - GLS and - degree of mitral regurgitation
10. Observed value and change from baseline in cardiac biomarker NT-proBNP
11. Observed value and change from baseline in the KCCQ as assessed by a 15-item, self-administered instrument that quantifies physical function, symptoms (frequency, severity, and recent change), social function, self-efficacy and knowledge, and QOL

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Askbio Inc.

Sponsor organisation

Askbio Inc.

Address

20 Tw Alexander Drive Suite 110

City

Durham

Postcode

27713-2928

Country

United States

Scientific contact point

Organisation

Askbio Inc.

Contact name

Luke Roberts

Public contact point

Organisation

Askbio Inc.

Contact name

Luke Roberts

Third parties 1

Sponsor responsibilities

Article 77 compliance

Askbio Inc.

Contact point sponsor

Askbio Inc.

Article 77 implementation

Askbio Inc.

Locations

9 EU/EEA countries · 54 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 124 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

32 submissions — initial application plus substantial / non-substantial modifications