NAN-101 for Heart Failure
(NAN-CS101 Trial)
Recruiting in Palo Alto (17 mi)
+3 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: AskBio Inc
Must be taking: Beta blockers, ACE inhibitors
Disqualifiers: Ischemic cardiomyopathy, Cardiac surgery, others
No Placebo Group
Approved in 1 jurisdiction
Trial Summary
What is the purpose of this trial?This trial tests a new heart treatment given directly into the heart's blood vessels. It aims to help patients with severe heart failure who have significant symptoms and limited physical activity. The treatment is designed to improve heart function and quality of life.
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.
What evidence supports the effectiveness of the drug NAN-101 for heart failure?
Research shows that B-type natriuretic peptide (BNP), which is similar to nesiritide, is effective in treating heart failure by helping to reduce pressure in the heart and improve symptoms. Nesiritide, a synthetic form of BNP, has been shown to be effective in clinical trials for heart failure, suggesting that similar treatments like NAN-101 may also be beneficial.
12345What makes the drug NAN-101 unique for treating heart failure?
NAN-101 is unique because it involves the use of natriuretic peptides, which are hormones that help regulate blood pressure and fluid balance, and have potential therapeutic effects in heart failure by counteracting harmful hormonal systems. This approach is different from traditional treatments that primarily focus on suppressing these systems.
16789Eligibility Criteria
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.
+5 more
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.
+18 more
Trial Timeline
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)
Participant Groups
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.
3Treatment groups
Experimental Treatment
Group I: PLN-R14Del patients: 3.25E13vg AB-1002Experimental Treatment1 Intervention
Intracoronary Infusion of AB-1002 at 3.25E13vg up to 6 subjects with PLN-R14Del genetic mutation
Group II: 3.25E13vg AB-1002Experimental Treatment1 Intervention
Intracoronary Infusion of 3.25E13vg AB-1002 up to 6 subjects
Group III: 1.08E14vg AB-1002Experimental Treatment1 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
The Linder Center for Education and Research at The Christ HospitalCincinnati, OH
University of Wisconsin at MadisonMadison, WI
The Ohio State UniversityColumbus, OH
Minneapolis Heart Foundation InstituteMinneapolis, MN
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Who Is Running the Clinical Trial?
AskBio IncLead Sponsor
Asklepios Biopharmaceutical, Inc.Lead Sponsor
References
The role of b-type natriuretic peptide in heart failure management. [2015]Heart failure is a complex clinical syndrome that manifests itself with signs and symptoms which are neither sensitive nor specific for the diagnosis of heart failure. Natriuretic peptides and in particular b-type natriuretic peptide (and nt-proBNP) are widely used in clinical practice around the world as a maker of heart failure. BNP is primarily released from the left ventricle in response to pressure and volume overload. The strongest evidence for the use of BNP is to rule in or rule out heart failure as cause of breathlessness in people who present to the emergency room. There is enthusiasm for use of BNP as a marker of heart failure severity as well as a predictor of outcomes in people with heart failure and trials are ongoing. Nesiritide, a recombinant form of BNP is currently being tested as a possible treatment in people with acutely decompensated heart failure.
Novel protein therapeutics for systolic heart failure: chronic subcutaneous B-type natriuretic peptide. [2021]The purpose of the present study was to translate our laboratory investigations to establish safety and efficacy of 8 weeks of chronic SC B-type natriuretic peptide (BNP) administration in human Stage C heart failure (HF).
The role of B-type natriuretic peptide in heart failure. [2019]The use of BNP as a diagnostic and therapeutic tool in the management of heart failure is promising. Additional studies need to be done regarding the use of BNP as a diagnostic tool to clarify its intrapatient and interpatient variability, especially over time. Nesiritide is the first new intravenous agent for the treatment of acute decompensated heart failure since the introduction of milrinone. It is an effective vasodilator and enhances the effect of concomitant diuretic therapy. Nesiritide may have some benefit on long-term outcomes by prolonging survival, decreasing hospitalizations, or enhancing quality of life. Whether it can or should be used as chronic therapy in end-stage patients remains to be determined.
Brain natriuretic peptide usefulness in very elderly dyspnoeic patients: the BED study. [2018]To evaluate the interest of brain natriuretic peptide (BNP) for heart failure (HF) diagnosis in very old patients.
Brain natriuretic peptide (nesiritide) in the treatment of heart failure. [2019]Over the last decade brain natriuretic peptide (BNP) emerged as a cardiac hormone of clinical interest in diagnosis, prognosis and treatment of patients with Heart Failure (HF). The diagnostic potential of BNP is now well established both in patients with suspected HF as well as in patients with asymptomatic left ventricular systolic dysfunction. The prognostic information obtained from BNP levels in HF and acute myocardial infarction patients seems even more promising. Nesiritide is a synthetic peptide, homologous to endogenous BNP. It is a balanced vasodilator with diuretic and natriuretic properties. It decreases the elevated levels of neurohormones resulting from activation of the sympathetic and renin-aldosterone systems in HF. The results of clinical trials involving more than 2000 patients with decompensated HF are now available. In these trials nesiritide was administered by single or repeated bolus injections, as well as by sustained infusions. Nesiritide has been shown to produce a potent, dose-related vasodilator effect that is rapid in onset and sustained during infusion. Balanced vasodilation is reflected by decreases in systemic vascular resistance, pulmonary artery wedge pressure and right atrial pressure. No tachyphylaxis has been observed in these trials. Efficacy of nesiritide in the treatment of decompensated HF has been demonstrated. Trials comparing nesiritide with conventional treatment of decompensated HF showed that nesiritide compares favorably to standard agents. The safety profile has been excellent with a dose-dependent hypotension as the major side effect. Ventricular arrhythmia was not more frequent in patients treated with nesiritide than with placebo. Thus, nesiritide appears to be useful as a first-line agent in the treatment of patients with decompensated HF.
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. [2023]Natriuretic peptides, brain (B-type) natriuretic peptide (BNP) and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) are globally and most often used for the diagnosis of heart failure (HF). In addition, they can have an important complementary role in the risk stratification of its prognosis. Since the development of angiotensin receptor neprilysin inhibitors (ARNIs), the use of natriuretic peptides as therapeutic agents has grown in importance. The present document is the result of the Trilateral Cooperation Project among the Heart Failure Association of the European Society of Cardiology, the Heart Failure Society of America and the Japanese Heart Failure Society. It represents an expert consensus that aims to provide a comprehensive, up-to-date perspective on natriuretic peptides in the diagnosis and management of HF, with a focus on the following main issues: (1) history and basic research: discovery, production and cardiovascular protection; (2) diagnostic and prognostic biomarkers: acute HF, chronic HF, inclusion/endpoint in clinical trials, and natriuretic peptides-guided therapy; (3) therapeutic use: nesiritide (BNP), carperitide (ANP) and ARNIs; and (4) gaps in knowledge and future directions.
Evolving Role of Natriuretic Peptides from Diagnostic Tool to Therapeutic Modality. [2018]Natriuretic peptides (NP) are widely recognized as key regulators of blood pressure, water and salt homeostasis. In addition, they play a critical role in physiological cardiac growth and mediate a variety of biological effects including antiproliferative and anti-inflammatory effects in other organs and tissues. The cardiac release of NPs ANP and BNP represents an important compensatory mechanism during acute and chronic cardiac overload and during the pathogenesis of heart failure where their actions counteract the sustained activation of renin-angiotensin-aldosterone and other neurohormonal systems. Elevated circulating plasma NP levels correlate with the severity of heart failure and particularly BNP and the pro-peptide, NT-proBNP have been established as biomarkers for the diagnosis of heart failure as well as prognostic markers for cardiovascular risk. Despite activation of the NP system in heart failure it is inadequate to prevent progressive fluid and sodium retention and cardiac remodeling. Therapeutic approaches included administration of synthetic peptide analogs and the inhibition of NP-degrading enzyme neutral endopeptidase (NEP). Of all strategies only the combined NEP/ARB inhibition with sacubitril/valsartan had shown clinical success in reducing cardiovascular mortality and morbidity in patients with heart failure.
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. [2023]Natriuretic peptides, brain (B-type) natriuretic peptide (BNP) and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) are globally and most often used for the diagnosis of heart failure (HF). In addition, they can have an important complementary role in the risk stratification of its prognosis. Since the development of angiotensin receptor-neprilysin inhibitors (ARNIs), the use of natriuretic peptides as therapeutic agents has grown in importance. The present document is the result of the Trilateral Cooperation Project among the Heart Failure Association of the European Society of Cardiology, the Heart Failure Society of America and the Japanese Heart Failure Society. It represents an expert consensus that aims to provide a comprehensive, up-to-date perspective on natriuretic peptides in the diagnosis and management of HF, with a focus on the following main issues: (1) history and basic research: discovery, production and cardiovascular protection; (2) diagnostic and prognostic biomarkers: acute HF, chronic HF, inclusion/endpoint in clinical trials, and natriuretic peptide-guided therapy; (3) therapeutic use: nesiritide (BNP), carperitide (ANP) and ARNIs; and (4) gaps in knowledge and future directions.
Synthesis, secretion, function, metabolism and application of natriuretic peptides in heart failure. [2023]As a family of hormones with pleiotropic effects, natriuretic peptide (NP) system includes atrial NP (ANP), B-type NP (BNP), C-type NP (CNP), dendroaspis NP and urodilatin, with NP receptor-A (guanylate cyclase-A), NP receptor-B (guanylate cyclase-B) and NP receptor-C (clearance receptor). These peptides are genetically distinct, but structurally and functionally related for regulating circulatory homeostasis in vertebrates. In humans, ANP and BNP are encoded by NP precursor A (NPPA) and NPPB genes on chromosome 1, whereas CNP is encoded by NPPC on chromosome 2. NPs are synthesized and secreted through certain mechanisms by cardiomyocytes, fibroblasts, endotheliocytes, immune cells (neutrophils, T-cells and macrophages) and immature cells (embryonic stem cells, muscle satellite cells and cardiac precursor cells). They are mainly produced by cardiovascular, brain and renal tissues in response to wall stretch and other causes. NPs provide natriuresis, diuresis, vasodilation, antiproliferation, antihypertrophy, antifibrosis and other cardiometabolic protection. NPs represent body's own antihypertensive system, and provide compensatory protection to counterbalance vasoconstrictor-mitogenic-sodium retaining hormones, released by renin-angiotensin-aldosterone system (RAAS) and sympathetic nervous system (SNS). NPs play central roles in regulation of heart failure (HF), and are inactivated through not only NP receptor-C, but also neutral endopeptidase (NEP), dipeptidyl peptidase-4 and insulin degrading enzyme. Both BNP and N-terminal proBNP are useful biomarkers to not only make the diagnosis and assess the severity of HF, but also guide the therapy and predict the prognosis in patients with HF. Current NP-augmenting strategies include the synthesis of NPs or agonists to increase NP bioactivity and inhibition of NEP to reduce NP breakdown. Nesiritide has been established as an available therapy, and angiotensin receptor blocker NEP inhibitor (ARNI, LCZ696) has obtained extremely encouraging results with decreased morbidity and mortality. Novel pharmacological approaches based on NPs may promote a therapeutic shift from suppressing the RAAS and SNS to re-balancing neuroendocrine dysregulation in patients with HF. The current review discussed the synthesis, secretion, function and metabolism of NPs, and their diagnostic, therapeutic and prognostic values in HF.