NAN-101 for Heart Failure

(NAN-CS101 Trial)

Not currently recruiting at 3 trial locations

Overseen By AskBio Medical Affairs

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: AskBio Inc

Must be taking: Beta blockers, ACE inhibitors

Disqualifiers: Ischemic cardiomyopathy, Cardiac surgery, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: 8

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called NAN-101, a gene therapy, to determine its safety and effectiveness for individuals with serious heart failure not caused by blocked heart arteries. The study involves a one-time infusion into the heart to evaluate its efficacy and any side effects. It seeks participants who have experienced severe heart failure symptoms for at least three months despite current treatments. Researchers will follow participants for about a year to assess their response to the treatment. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial requires that your current heart failure medications, like beta blockers and ACE inhibitors, be stable for at least 30 days before joining. It doesn't specify stopping other medications, so you should discuss your specific situation with the trial team.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that the treatment AB-1002 underwent safety testing in earlier studies, specifically for heart failure. Initial results suggested that AB-1002 was generally well-tolerated, with most patients not experiencing serious side effects directly caused by the treatment. However, as this is an early-stage study, the primary goal is to ensure the treatment's safety. More information is needed to fully understand its effects. Always consult a healthcare provider to determine if joining a trial is appropriate. ^{1 2 3 4 5}

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

Most treatments for heart failure focus on managing symptoms and improving heart function through medications like ACE inhibitors, beta-blockers, and diuretics. However, NAN-101 is unique because it uses a gene therapy approach, specifically targeting the PLN-R14Del genetic mutation, which is often linked to heart failure. This treatment involves an intracoronary infusion of AB-1002 at varying doses, aiming to directly address genetic causes rather than just alleviating symptoms. Researchers are excited because NAN-101 has the potential to offer a more targeted and long-lasting solution for patients with this specific genetic mutation, potentially transforming how heart failure is treated.

What evidence suggests that NAN-101 might be an effective treatment 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 experienced improvements in heart failure symptoms and demonstrated better heart function, specifically in how well the heart pumps blood. These findings suggest that AB-1002 could aid those with more severe heart failure, offering hope for better management of symptoms. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for adults over 18 with Class III heart failure who've had symptoms despite treatment for at least 6 months. They must have a left ventricular ejection fraction (LVEF) ≤30% and be able to consent. Women of childbearing age and men must agree to use contraception during the study and for six months after.

Inclusion Criteria

I am older than 18 years.

Your heart's pumping ability is very low, as measured by a recent heart ultrasound.

I am a man who can father a child and agree to use a condom for 6 months after treatment.

Exclusion Criteria

I have anemia or needed a blood transfusion in the last 30 days.

I haven't taken part in another clinical study or taken any investigational drugs within the last 30 days.

I am allergic to dyes used in certain heart and blood vessel imaging tests.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Single intracoronary infusion of AB-1002

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Multiple visits (in-person and virtual)

Long-term follow-up

Participants undergo long-term follow-up via semi-structured telephone questionnaires

24 months

Every 6 months (virtual)

What Are the Treatments Tested in This Trial?

Interventions

• NAN-101

Trial Overview

The trial tests a single intracoronary infusion of NAN-101 in patients with symptomatic congestive heart failure, monitoring them for safety, feasibility, and efficacy over a period of up to three years including follow-ups via phone every six months after the first year.

How Is the Trial Designed?

Group I: PLN-R14Del patients: 3.25E13vg AB-1002 Experimental Treatment 1 Intervention

Intracoronary Infusion of AB-1002 at 3.25E13vg up to 6 subjects with PLN-R14Del genetic mutation

Group II: 3.25E13vg AB-1002 Experimental Treatment 1 Intervention

Intracoronary Infusion of 3.25E13vg AB-1002 up to 6 subjects

Group III: 1.08E14vg AB-1002 Experimental Treatment 1 Intervention

Intracoronary Infusion of 1.08E14vg AB-1002 to 6 subjects

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

Natriuretic peptides, particularly BNP and NT-proBNP, are essential for diagnosing heart failure and can also help assess the prognosis of patients, making them valuable biomarkers in clinical settings.

The introduction of angiotensin receptor-neprilysin inhibitors (ARNIs) has increased the therapeutic relevance of natriuretic peptides, highlighting their potential role not just in diagnosis but also in the treatment of heart failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Natriuretic peptides: role in the diagnosis and management of heart failure: a scientific statement from the Heart Failure Association of the European Society of Cardiology, Heart Failure Society of America and Japanese Heart Failure Society. Tsutsui, H., Albert, NM., Coats, AJS., et al.[2023]

Natriuretic peptides (NPs) like ANP and BNP play crucial roles in regulating heart failure by promoting natriuresis, diuresis, and vasodilation, acting as the body's natural antihypertensive system.

Current therapies, such as nesiritide and ARNI (LCZ696), have shown promising results in reducing morbidity and mortality in heart failure patients by enhancing NP activity and counteracting the effects of the renin-angiotensin-aldosterone system.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synthesis, secretion, function, metabolism and application of natriuretic peptides in heart failure. Fu, S., Ping, P., Wang, F., et al.[2023]

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]

Nesiritide, a synthetic version of brain natriuretic peptide (BNP), has been shown to effectively treat decompensated heart failure (HF) in over 2000 patients, demonstrating a rapid and sustained vasodilator effect without tachyphylaxis.

The safety profile of nesiritide is excellent, with dose-dependent hypotension as the main side effect, and it does not increase the risk of ventricular arrhythmias compared to placebo, making it a promising first-line treatment option for decompensated HF.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brain natriuretic peptide (nesiritide) in the treatment of heart failure. Bettencourt, P.[2019]

Natriuretic peptides, particularly BNP and NT-proBNP, are essential for diagnosing heart failure and can also help assess the prognosis of patients, making them valuable biomarkers in clinical settings.

The introduction of angiotensin receptor neprilysin inhibitors (ARNIs) has increased the therapeutic relevance of natriuretic peptides, highlighting their potential role not just in diagnosis but also in the treatment of heart failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Natriuretic Peptides: Role in the Diagnosis and Management of Heart Failure: A Scientific Statement From the Heart Failure Association of the European Society of Cardiology, Heart Failure Society of America and Japanese Heart Failure Society. Tsutsui, H., Albert, NM., Coats, AJS., et al.[2023]

Natriuretic peptides (NPs), particularly ANP and BNP, are crucial for regulating blood pressure and fluid balance, and their levels increase in response to heart failure, serving as important biomarkers for diagnosis and prognosis.

The combination therapy of sacubitril/valsartan, which inhibits the enzyme that degrades NPs, has been clinically successful in reducing cardiovascular mortality and morbidity in heart failure patients, highlighting its efficacy compared to other therapeutic approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evolving Role of Natriuretic Peptides from Diagnostic Tool to Therapeutic Modality. Pagel-Langenickel, I.[2018]

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]

B-type natriuretic peptide (BNP) shows promise as a diagnostic and therapeutic tool for heart failure, but more research is needed to understand its variability in patients over time.

Nesiritide, a new intravenous treatment for acute heart failure, effectively acts as a vasodilator and may improve long-term outcomes, although its role in chronic therapy for end-stage patients is still uncertain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of B-type natriuretic peptide in heart failure. Nappi, JM.[2019]

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

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AskBio Announces Publication in Nature Medicine of 12 ...

AskBio Announces Publication in Nature Medicine of 12-month data from Phase 1 Trial of AB-1002 Gene Therapy in Participants with Congestive ...

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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 ...

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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).

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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.