AB-1002 for Heart Failure

(GenePHIT Trial)

Recruiting at 107 trial locations

Overseen By Medical Affairs

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: AskBio Inc

Must be taking: Beta blockers, ACE inhibitors

Disqualifiers: Ischemic cardiomyopathy, Cardiac surgery, Liver disease, Kidney disease, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1 day

150 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called AB-1002 (also known as NAN-101) to determine its effectiveness for people with heart failure due to non-ischemic cardiomyopathy, where the heart muscle weakens without blocked arteries. Researchers aim to assess the safety and effectiveness of a one-time dose of AB-1002, administered directly into the heart. Participants will join one of three groups to receive varying doses of the treatment or a placebo for comparison. Ideal candidates have non-ischemic cardiomyopathy, significant heart failure symptoms (NYHA Class III), and have maintained stability on current heart medications for at least four weeks. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to significant advancements in heart failure treatment.

Do I need to stop my current medications for this trial?

The trial requires that you stay on your current heart failure medications, such as beta blockers and ACE inhibitors, for at least 90 days before joining. Your medication doses must be stable for at least 30 days before enrollment.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Studies have shown that AB-1002 may be safe and well-tolerated in people with heart failure. Earlier research linked both doses of AB-1002 to positive effects and found that most people did not experience serious side effects.

In one study, researchers closely monitored participants after administering AB-1002 directly into a heart artery. This method proved generally safe and workable. While some participants experienced minor side effects, the treatment did not raise major safety concerns.

These findings provide confidence in the safety of AB-1002 for those considering joining a clinical trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for heart failure?

Researchers are excited about AB-1002 for heart failure because it uses a novel gene therapy approach, delivering genetic material to heart cells to potentially improve their function. Unlike the standard treatments, which typically involve medications like ACE inhibitors or beta-blockers that manage symptoms, AB-1002 directly targets the underlying causes of heart dysfunction. This direct targeting could lead to more effective and longer-lasting improvements in heart health. Additionally, the unique vector dosage used in AB-1002 might offer a tailored approach that optimizes the treatment's effectiveness and safety for individual patients.

What evidence suggests that this trial's treatments could be effective for heart failure?

Research has shown that AB-1002, which participants in this trial may receive, may help treat heart failure. In earlier studies, patients who received this treatment demonstrated better heart function. Specifically, their heart failure symptoms improved, as measured by the New York Heart Association (NYHA) class. There were also positive changes in their heart's ability to pump blood, known as the left ventricular ejection fraction (LVEF). Additionally, patients performed better on exercise tests, such as the 6-minute walk test, which measures how far they can walk in six minutes. These findings suggest that AB-1002 could be effective for people with heart failure. ^{1 3 4 5 6}

Are You a Good Fit for This Trial?

Adults over 18 with non-ischemic cardiomyopathy and NYHA Class III heart failure symptoms, who can walk more than 50 meters. They must have a left ventricular ejection fraction of 15-35%, be on stable heart medications, and if applicable, use reliable contraception. Excluded are those with recent severe heart issues, other serious health conditions or treatments that could interfere with the study.

Inclusion Criteria

My heart condition has been stable for at least 4 weeks, and I've been on specific heart medications for over 3 months.

I have been diagnosed with a long-term heart muscle disease not caused by blocked arteries.

My heart device was implanted at least 90 days ago, if it's for resynchronization, or 30 days ago for a defibrillator.

Exclusion Criteria

I have a severe type of heart rhythm problem.

I am HIV positive or have AIDS with low immunity.

I do not have specific heart or thyroid conditions.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single dose of AB-1002 or placebo via intracoronary artery infusion

1 day

1 visit (in-person)

Observation

Participants are monitored for safety and efficacy with primary analysis at 52 weeks

52 weeks

Regular visits as per study protocol

Long-term Follow-up

Participants are contacted for safety, efficacy assessments, and survival

4 years

Twice a year for two years, then once a year for two years

What Are the Treatments Tested in This Trial?

Interventions

• NAN-101

Trial Overview The trial is testing AB-1002's safety and effectiveness for heart failure when given through an artery in the heart. Participants will be randomly assigned to one of three groups to receive either AB-1002 or a placebo in equal ratios.

How Is the Trial Designed?

Group I: Treatment Group 2 AB-1002 Experimental Treatment 1 Intervention

Randomized in 1:1:1 into one of three groups. Group 2: 6.5E13vg (n=30-50)

Group II: AB-1002 Experimental Treatment 1 Intervention

Randomized in 1:1:1 into one of three groups. Group 1: 3.25E13vg (n=30-50)

Group III: Treatment Group 3 Placebo Group 1 Intervention

Randomized in 1:1:1 into one of three groups. Group 3: Placebo (n=30-50)

NAN-101 is already approved in United States for the following indications:

Approved in United States as NAN-101 for:

• None approved yet; currently in Phase 1 trial for Heart Failure

Who Is Running the Clinical Trial?

AskBio Inc

Lead Sponsor

Trials

8

Recruited

440+

Asklepios Biopharmaceutical, Inc.

Lead Sponsor

Trials

8

Recruited

440+

Published Research Related to This Trial

In the PARADIGM-HF trial, the ratio of NT-proBNP to BNP in patients with heart failure and reduced ejection fraction was found to be approximately 6.25:1, which varies significantly based on factors like age and renal function, indicating that these peptides should be interpreted with these variables in mind.

Both NT-proBNP and BNP were similarly effective in predicting outcomes such as cardiovascular death and heart failure hospitalization, suggesting that either peptide can be reliably used for assessing patient prognosis in heart failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of BNP and NT-proBNP in Patients With Heart Failure and Reduced Ejection Fraction. Rørth, R., Jhund, PS., Yilmaz, MB., et al.[2020]

In a study of 69 patients with heart failure, treatment guided by plasma levels of N-BNP resulted in significantly fewer cardiovascular events compared to standard clinical assessment, with 19 events in the N-BNP group versus 54 in the clinical group over a median follow-up of 9.5 months.

Patients receiving N-BNP-guided treatment experienced a delay in their first cardiovascular event (27% vs 53% at 6 months), suggesting that using N-BNP levels for treatment decisions may lead to better outcomes in managing heart failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of heart failure guided by plasma aminoterminal brain natriuretic peptide (N-BNP) concentrations. Troughton, RW., Frampton, CM., Yandle, TG., et al.[2022]

Nesiritide is an intravenous treatment for acutely decompensated heart failure that effectively reduces heart pressure and improves symptoms, while also providing modest diuretic effects.

Ongoing clinical trials are investigating the long-term safety and potential benefits of nesiritide in various situations, including cardiac surgery and conditions like pulmonary hypertension and renal insufficiency.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current and future uses of nesiritide. Hobbs, RE., Tang, W.[2009]

Chronic subcutaneous administration of B-type natriuretic peptide (BNP) for 8 weeks in patients with Stage C heart failure significantly reduced left ventricular volumes and mass, indicating improved heart function.

The treatment also led to better patient-reported outcomes, such as improved Minnesota Living with Heart Failure scores, while preserving kidney function, suggesting that BNP is a safe and effective therapeutic option for heart failure management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel protein therapeutics for systolic heart failure: chronic subcutaneous B-type natriuretic peptide. Chen, HH., Glockner, JF., Schirger, JA., et al.[2021]

In a study involving 20 Yorkshire pigs with chronic heart failure, overexpression of the inhibitor-1 (I-1c) gene using a specially engineered adeno-associated virus (BNP116) significantly improved heart function, as shown by an increase in left ventricular ejection fraction by 5.7% in the high-dose group.

The gene therapy not only enhanced overall cardiac performance but also demonstrated a favorable gene expression pattern for targeting the heart, suggesting its potential as a promising treatment for advanced heart failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiac I-1c overexpression with reengineered AAV improves cardiac function in swine ischemic heart failure. Ishikawa, K., Fish, KM., Tilemann, L., et al.[2021]

B-type natriuretic peptide (BNP) and its precursor nt-proBNP are effective biomarkers for diagnosing heart failure, particularly useful in emergency settings to determine the cause of breathlessness.

Nesiritide, a recombinant form of BNP, is being investigated as a potential treatment for patients with acutely decompensated heart failure, highlighting ongoing research into BNP's therapeutic applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of b-type natriuretic peptide in heart failure management. Newton, PJ., Betihavas, V., Macdonald, P.[2015]

ARNI therapy leads to a decrease in N-terminal pro-BNP (NT-proBNP) and an increase in B-type natriuretic peptide (BNP) levels, which are associated with improved heart function in patients with heart failure with reduced ejection fraction (HFrEF).

The changes in BNP and NT-proBNP levels during ARNI therapy correlate with better echocardiographic parameters, suggesting that these biomarkers are important for monitoring cardiovascular outcomes and the effectiveness of the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Angiotensin Receptor-Neprilysin Inhibitors and the Natriuretic Peptide Axis. Vasquez, N., Carter, S., Grodin, JL.[2021]

Nesiritide is a safe and effective vasodilator for patients with acute decompensated heart failure (ADHF) who are already receiving optimal doses of loop diuretics, as supported by recent clinical trials.

Despite some ongoing controversy regarding its overall efficacy, nesiritide has properties that counteract the harmful processes of heart failure and is recommended as an additive therapy for symptomatic patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Natriuretic peptides for the treatment of acute heart failure: a focus on nesiritide in recent clinical trials. Fajardo, J., Heywood, JT., Patterson, JH., et al.[2015]

In a 6-year study involving 3,777 patients with acute heart failure, 82% showed clinical improvement after treatment with carperitide, indicating its efficacy in real-world settings.

The treatment was associated with a 16.9% incidence of adverse events, primarily low blood pressure, but most patients recovered without specific treatment, highlighting the need for careful monitoring during administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicenter prospective investigation on efficacy and safety of carperitide for acute heart failure in the 'real world' of therapy. Suwa, M., Seino, Y., Nomachi, Y., et al.[2019]

The 2021 European Society of Cardiology guidelines recommend a new approach for treating heart failure with reduced ejection fraction (HFrEF) by using four key drug classes simultaneously, rather than sequentially, to improve patient outcomes.

New treatments like vericiguat, which helps patients recently hospitalized for heart failure, and cardiac myosin activators and inhibitors (like omecamtiv mecarbil, mavacamten, and aficamten) show promise in reducing heart failure events and improving functional capacity, indicating a shift towards more effective therapies for heart failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Heart Failure Knights. Mozzini, C., Pagani, M.[2023]

Heart failure (HF) is a growing issue, particularly among elderly patients, affecting nearly 15% of those over 75 years old, with survival rates after diagnosis comparable to some cancers.

The measurement of brain natriuretic peptide (BNP) is increasingly recognized as a valuable tool for diagnosing, treating, and assessing the prognosis of heart failure patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brain natriuretic peptide in heart failure and beyond. Mowla, MM., Bustami, BB.[2008]

Conventional assays for BNP in heart failure, such as Roche NT-pro-BNP, Biosite Triage, and Shionogi, cannot effectively differentiate between various molecular forms of BNP, which may lead to incomplete identification of circulating BNP in heart failure patients.

In vitro studies showed that while the active BNP 1-32 and its cleavage product BNP 3-32 can activate cGMP in cardiac cells, the pro-BNP 1-108 and NT-pro-BNP 1-76 forms have significantly lower cGMP activity, suggesting they may have reduced biological effects in heart failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunoreactivity and guanosine 3',5'-cyclic monophosphate activating actions of various molecular forms of human B-type natriuretic peptide. Heublein, DM., Huntley, BK., Boerrigter, G., et al.[2016]

In a study of 383 patients aged 80 and older with acute dyspnoea, BNP levels were significantly higher in those with cardiac dyspnoea compared to those with respiratory dyspnoea, indicating a potential link between BNP levels and heart failure.

Despite this association, BNP alone did not effectively distinguish between cardiac and respiratory causes of dyspnoea, suggesting limited clinical utility in diagnosing heart failure in very old patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brain natriuretic peptide usefulness in very elderly dyspnoeic patients: the BED study. Plichart, M., Orvoën, G., Jourdain, P., et al.[2018]

Citations

1. askbio.com askbio.com/askbio-presents-complete-results-of-phase-1-trial-of-ab-1002-gene-therapy-in-participants-with-congestive-heart-failure-at-european-society-of-cardiology-heart-failure-meeting/

AskBio Presents Complete Results of Phase 1 Trial of AB ... The complete dataset from a Phase 1 trial investigating AB-1002 for the treatment of congestive heart failure (CHF).

2. nature.com nature.com/articles/s41591-025-04011-z

Cardiotropic AAV gene therapy for heart failure: a phase 1 ... Efficacy outcomes for cohorts 1 and 2, including NYHA class, LVEF, maximal oxygen consumption (pVO2) and 6-min walk test (6MWT), were improved ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/41120766/

Cardiotropic AAV gene therapy for heart failure: a phase 1 ... The preliminary assessments of efficacy outcomes showed improvements in the New York Heart Association class and left ventricular ejection ...

4. academic.oup.com academic.oup.com/eurheartj/article/45/Supplement_1/ehae666.3642/7838362

GenePHIT phase 2 study design: a double blind, placebo ... Here we describe the design of AB-1002 Ph 2 trial (GenePHIT; NCT05598333) to evaluate efficacy, safety, and tolerability.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04179643

NCT04179643 | AB-1002 in Patients With Class III Heart ... This is a Phase 1, prospective, multi-center, open-label, sequential dose escalation study to explore the safety, feasibility, and efficacy of a single ...

6. askbio.com askbio.com/askbio-announces-publication-in-nature-medicine-of-12-month-data-from-phase-1-trial-of-ab-1002-gene-therapy-in-participants-with-congestive-heart-failure/

AskBio Announces Publication in Nature Medicine of 12 ... First-in-human trial of investigational gene therapy AB-1002 designed to evaluate safety and preliminary efficacy in participants with New ...