AB-1002 for Heart Failure

(GenePHIT Trial)

Recruiting in Palo Alto (17 mi)

+44 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: AskBio Inc

Must be taking: Beta blockers, ACE inhibitors

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

Prior Safety Data

Approved in 1 Jurisdiction

Trial Summary

What is the purpose of this trial?

This is a Phase 2 adaptive, double-blinded, placebo-controlled, randomized, multi-center trial study to evaluate the safety and efficacy of a single dose of AB-1002, administered via antegrade intracoronary artery infusion, in males and females age \>18 years with non-ischemic cardiomyopathy and NYHA Class III symptoms of HF. Subjects will be randomized into one of three treatment groups in a 1:1:1

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.

What data supports the idea that AB-1002 for Heart Failure is an effective treatment?

The available research shows that B-type natriuretic peptide (BNP), which is related to AB-1002, is useful in diagnosing and managing heart failure. BNP is released by the heart when it is under stress, and it helps doctors understand how severe heart failure is. While the studies mention BNP's role in diagnosis and prognosis, they do not provide specific data on AB-1002's effectiveness as a treatment for heart failure. Therefore, there is no direct evidence from the provided information that AB-1002 is an effective treatment for heart failure. ^{1 2 3 4 5}

What safety data is available for AB-1002 in heart failure treatment?

The provided research does not contain specific safety data for AB-1002 or its other names (NAN-101, BNP116.sc-CMV.I1c, Carfostin, AAV2i8.I-1c). The studies focus on other treatments like carperitide and nesiritide, which are related to natriuretic peptides but do not directly address the safety of AB-1002. Therefore, no relevant safety data for AB-1002 is available in the provided research. ^{6 7 8 9 10}

Is the treatment AB-1002 for Heart Failure a promising treatment?

Yes, AB-1002, which involves using a gene therapy called NAN-101, shows promise for treating heart failure. In a study with pigs, this treatment improved heart function by increasing the heart's ability to pump blood. This suggests it could be a valuable option for people with heart failure. ^{3 4 11 12 13}

Research Team

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• NAN-101 (Phosphatase Inhibitor)

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.

Participant Groups

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)

Who Is Running the Clinical Trial?

AskBio Inc

Lead Sponsor

Trials

8

Recruited

440+

Asklepios Biopharmaceutical, Inc.

Lead Sponsor

Trials

8

Recruited

440+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

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 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]

References

1. England pubmed.ncbi.nlm.nih.gov

Treatment of heart failure guided by plasma aminoterminal brain natriuretic peptide (N-BNP) concentrations. [2022]

2. Saudi Arabia pubmed.ncbi.nlm.nih.gov

Brain natriuretic peptide in heart failure and beyond. [2008]

3. Australia pubmed.ncbi.nlm.nih.gov

The role of b-type natriuretic peptide in heart failure management. [2015]

4. United States pubmed.ncbi.nlm.nih.gov

Novel protein therapeutics for systolic heart failure: chronic subcutaneous B-type natriuretic peptide. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Brain natriuretic peptide usefulness in very elderly dyspnoeic patients: the BED study. [2018]

6. Japan pubmed.ncbi.nlm.nih.gov

Multicenter prospective investigation on efficacy and safety of carperitide for acute heart failure in the 'real world' of therapy. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

Angiotensin Receptor-Neprilysin Inhibitors and the Natriuretic Peptide Axis. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Natriuretic peptides for the treatment of acute heart failure: a focus on nesiritide in recent clinical trials. [2015]

9. Netherlands pubmed.ncbi.nlm.nih.gov

The Heart Failure Knights. [2023]

10. England pubmed.ncbi.nlm.nih.gov

Current and future uses of nesiritide. [2009]

11. United States pubmed.ncbi.nlm.nih.gov

Cardiac I-1c overexpression with reengineered AAV improves cardiac function in swine ischemic heart failure. [2021]

12. United States pubmed.ncbi.nlm.nih.gov

Immunoreactivity and guanosine 3',5'-cyclic monophosphate activating actions of various molecular forms of human B-type natriuretic peptide. [2016]

13. United States pubmed.ncbi.nlm.nih.gov

Comparison of BNP and NT-proBNP in Patients With Heart Failure and Reduced Ejection Fraction. [2020]