AB-1002 for Heart Failure (GenePHIT Trial)
Palo Alto (17 mi)Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Asklepios Biopharmaceutical, Inc.
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
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.457811
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.2691213
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.135710
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.
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
I have been diagnosed with a long-term heart muscle disease not caused by blocked arteries.
My heart condition has been stable for at least 4 weeks, and I've been on specific heart medications for over 3 months.
I am 18 years old or older.
I can walk more than 50 meters in 6 minutes.
Exclusion Criteria
I have a severe type of heart rhythm problem.
I am HIV positive or have AIDS with low immunity.
I am allergic to dyes used in certain heart and blood vessel imaging tests.
I have advanced kidney disease and need dialysis or my kidney function is very low.
I do not have a bleeding disorder or low platelet count.
I have heart muscle damage due to blocked heart arteries.
I have a low white blood cell count.
I have a diagnosed liver condition.
I have not had heart surgery or a heart procedure in the last 30 days.
I have had heart surgery or a device implanted for heart support.
Treatment Details
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.
3Treatment groups
Experimental Treatment
Placebo Group
Group I: Treatment Group 2 AB-1002Experimental Treatment1 Intervention
Randomized in 1:1:1 into one of three groups.
Group 2: 6.5E13vg (n=30-50)
Group II: AB-1002Experimental Treatment1 Intervention
Randomized in 1:1:1 into one of three groups.
Group 1: 3.25E13vg (n=30-50)
Group III: Treatment Group 3Placebo Group1 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
Find a clinic near you
Research locations nearbySelect from list below to view details:
University of California San DiegoLa Jolla, CA
University of MiamiCoral Gables, FL
Augusta UniversityAugusta, GA
University of Kansas Medical Center (KUMC)Kansas City, KS
More Trial Locations
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Who is running the clinical trial?
Asklepios Biopharmaceutical, Inc.Lead Sponsor
References
Treatment of heart failure guided by plasma aminoterminal brain natriuretic peptide (N-BNP) concentrations. [2022]There is currently no objective practical guide to intensity of drug treatment for individuals with heart failure. We hypothesised that pharmacotherapy guided by plasma concentrations of the cardiac peptide aminoterminal brain natriuretic peptide (N-BNP) would produce a superior outcome to empirical trial-based therapy dictated by clinical acumen.
Multicenter prospective investigation on efficacy and safety of carperitide for acute heart failure in the 'real world' of therapy. [2019]Efficacy and safety assessments for carperitide (alpha-human atrial natriuretic peptide) in previous clinical trials have not mentioned its limitations in practice as therapy for acute heart failure.
Brain natriuretic peptide in heart failure and beyond. [2008]Hospital admissions with heart failure (HF) are increasing worldwide. It is the main reason for hospitalization of elderly patients. Heart failure affects nearly 15% of patients aged >75 years. Prognosis after diagnosis of HF is comparable to that of cancers with 50% survival after 4 years of mild HF and 50% after one year in more severe cases. Current data increasingly suggest that measurement of brain natriuretic peptide (BNP) is very useful in diagnosis, treatment, prognosis and risk stratification of patients with HF and beyond. This paper reviews the available literature concerning the BNP and N-terminal pro brain-type natriuretic peptide to assess their role in current medical practice.
Immunoreactivity and guanosine 3',5'-cyclic monophosphate activating actions of various molecular forms of human B-type natriuretic peptide. [2016]Recent studies support the speculation that different molecular forms of the cardiac hormone BNP with differential biological activity may circulate in heart failure and be detected by conventional assays. In the current study we determined the ability of 3 widely used conventional assays to detect these different forms thought to circulate in heart failure. We also evaluated the ability of pro-BNP (1-108), N-terminal peptide (NT)-pro-BNP (1-76), and BNP 3-32, the latter a cleavage product of BNP 1-32 by dipeptidyl peptidase IV, on an equimolar basis to activate cGMP in cultured cardiac fibroblasts and cardiomyocytes compared with the biologically active mature BNP 1-32. Specifically, we observed that the Roche NT-pro-BNP assay detected both NT-pro-BNP 1-76 and pro-BNP 1-108 and that Biosite Triage and Shionogi detected both mature BNP 1-32 and the shortened BNP 3-32. Moreover, in cultured cardiac fibroblasts and cardiomyocytes, BNP 1-32 (10(-6) mol/L) activated cGMP. BNP 3-32 demonstrated a similar cGMP activating property in both cardiac cell types. In contrast, the cGMP response to pro-BNP 1-108 and NT-pro-BNP 1-76 was not significantly greater than no treatment alone. We conclude that widely used commercial assays for NT-pro-BNP 1-76 and BNP 1-32 cannot differentiate among pro-, processed, or degraded forms and, thus, may not thoroughly identify circulating BNP forms in heart failure patients. These findings also demonstrate differential cGMP activating properties of BNP forms and, importantly, that pro-BNP 1-108 and NT-pro-BNP 1-76 have reduced cGMP activity in vitro that may have biological relevance to human heart failure.
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.
Current and future uses of nesiritide. [2009]Nesiritide, recombinant human B-type natriuretic peptide, is an intravenous vasodilator that is used to treat acutely decompensated heart failure. In addition to its modest diuretic and natriuretic properties, nesiritide reduces intracardiac filling pressures, increases cardiac index and improves symptoms. Long-term safety data are accruing, and a number of ongoing clinical trials will explore the potential benefit of nesiritide in a variety of clinical situations: peri-operative cardiac surgery, serial out-patient infusions, continuous out-patient or pretransplant infusions, and infusions in patients with pulmonary hypertension, bronchospasm, renal insufficiency, and acute coronary syndromes. Alternative delivery methods also are under development.
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).
Cardiac I-1c overexpression with reengineered AAV improves cardiac function in swine ischemic heart failure. [2021]Cardiac gene therapy has emerged as a promising option to treat advanced heart failure (HF). Advances in molecular biology and gene targeting approaches are offering further novel options for genetic manipulation of the cardiovascular system. The aim of this study was to improve cardiac function in chronic HF by overexpressing constitutively active inhibitor-1 (I-1c) using a novel cardiotropic vector generated by capsid reengineering of adeno-associated virus (BNP116). One month after a large anterior myocardial infarction, 20 Yorkshire pigs randomly received intracoronary injection of either high-dose BNP116.I-1c (1.0 × 10(13) vector genomes (vg), n = 7), low-dose BNP116.I-1c (3.0 × 10(12) vg, n = 7), or saline (n = 6). Compared to baseline, mean left ventricular ejection fraction increased by 5.7% in the high-dose group, and by 5.2% in the low-dose group, whereas it decreased by 7% in the saline group. Additionally, preload-recruitable stroke work obtained from pressure-volume analysis demonstrated significantly higher cardiac performance in the high-dose group. Likewise, other hemodynamic parameters, including stroke volume and contractility index indicated improved cardiac function after the I-1c gene transfer. Furthermore, BNP116 showed a favorable gene expression pattern for targeting the heart. In summary, I-1c overexpression using BNP116 improves cardiac function in a clinically relevant model of ischemic HF.
Natriuretic peptides for the treatment of acute heart failure: a focus on nesiritide in recent clinical trials. [2015]Nesiritide, a recombinant form of B-type natriuretic peptide, is a vasodilator and currently recommended as an additive therapy for patients with acute decompensated heart failure (ADHF) who have been optimized on loop diuretics. With hospitalizations for ADHF rising, appropriate selection of therapy becomes even more important to optimize efficacy and reduce adverse events. Nesiritide has many properties that antagonize the pathophysiologic processes of heart failure and has demonstrated a comparative benefit in previous reports; however, controversy still remains with respect to its efficacy and safety. Based on results from recent clinical trials, nesiritide has been shown to be safe at currently approved doses and strongly considered for the treatment of ADHF in patients who remain symptomatic despite optimal doses of intravenous loop divertics.
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.
Comparison of BNP and NT-proBNP in Patients With Heart Failure and Reduced Ejection Fraction. [2020]Both BNP (B-type natriuretic peptide) and NT-proBNP (N-terminal pro B-type natriuretic peptide) are widely used to aid diagnosis, assess the effect of therapy, and predict outcomes in heart failure and reduced ejection fraction. However, little is known about how these 2 peptides compare in heart failure and reduced ejection fraction, especially with contemporary assays. Both peptides were measured at screening in the PARADIGM-HF trial (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure).
Angiotensin Receptor-Neprilysin Inhibitors and the Natriuretic Peptide Axis. [2021]The purpose of this review is to describe the effects of angiotensin receptor neprilysin inhibitor (ARNI) therapy on the natriuretic peptide axis (NPA), with a particular focus on B-type natriuretic peptide (BNP), atrial natriuretic peptide (ANP), and C-type natriuretic peptide (CNP) to better understand the biology behind the improved outcomes in patients with heart failure with reduced ejection fraction (HFrEF).
The Heart Failure Knights. [2023]The 2021 European Society of Cardiology guidelines for the diagnosis and treatment of acute and chronic heart failure (HF) have abandoned the sequential approach for optimal drug therapy and proposed four drug classes, the so-called 4 "pillars" (angiotensin-converting enzyme inhibitors; angiotensin receptor-neprilysin inhibitors; beta-blockers; mineralocorticoid receptor antagonists and sodium-glucose co-transporter 2 inhibitors) to be initiated and titrated in all patients with reduced ejection fraction HF (HFrEF). In addition, new molecules have been considered, derived from recently reported advances from trials in HFrEF. In this review, Authors examine in particular these new molecules, as further "knights" for HF. In particular, vericiguat, a novel oral soluble guanylate cyclase stimulator, has proved effective in patients with HFrEF who had recently been hospitalized or had received intravenous diuretic therapy. The selective cardiac myosin activator omecamtiv mecarbil and the cardiac myosin inhibitors aficamten and mavacamten are under investigation. Cardiac myosin stimulator, omecamtiv mecarbil, has shown efficacy in HFrEF, lowering HF related events or cardiovascular death, while the 2 inhibitors, mavacamten and aficamten have been shown to reduce hypercontractility and left ventricular outflow obstruction improving functional capacity in randomized trials targeting hypertrophic cardiomyopathy. These agents are the prototypes of active pipelines promising to deliver an array of molecules against HF in the near future.