Ponsegromab for Heart Failure
(GARDEN TIMI 74 Trial)
Recruiting in Palo Alto (17 mi)
+139 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Waitlist Available
Sponsor: Pfizer
Prior Safety Data
Trial Summary
What is the purpose of this trial?
This trial is testing Ponsegromab, a new medicine, to see if it can help people with heart failure who have high levels of GDF-15. The medicine is given as an injection under the skin and aims to reduce heart failure symptoms by targeting the GDF-15 protein.
Do I have to stop taking my current medications for this trial?
The trial protocol does not specify if you need to stop taking your current medications. However, it does exclude participants who have used investigational products recently. It's best to discuss your specific medications with the trial team.
What data supports the idea that Ponsegromab for Heart Failure is an effective treatment?
The available research does not provide specific data on Ponsegromab for Heart Failure. Instead, it focuses on another drug called Vericiguat, which has shown effectiveness in reducing hospitalizations related to heart failure. Without specific data on Ponsegromab, we cannot compare its effectiveness to Vericiguat or other treatments for heart failure.12345
What safety data is available for Ponsegromab (PF-06946860) in heart failure treatment?
Eligibility Criteria
This trial is for adults with heart failure who experience symptoms like unintentional weight loss, fatigue, or physical limitations. They must have a left ventricular ejection fraction (LVEF) of less than 50% and elevated levels of certain heart-related biomarkers. People with recent major cardiac procedures, acute coronary syndrome, untreated rhythm disorders, severe liver disease not caused by heart failure, or those on dialysis cannot participate.Inclusion Criteria
I experience significant weight loss, fatigue, or difficulty performing daily tasks.
I am 18 years old or older.
I have experienced significant weight loss, fatigue, or physical limitations recently.
See 9 more
Exclusion Criteria
I have cirrhosis with signs of increased blood pressure in the liver not caused by heart failure.
You have had a heart transplant, are waiting for a heart transplant, are using or planning to use a mechanical heart pump, or are using or planning to use strong heart medications given through a vein.
I have had a heart attack or other heart issue in the last month.
See 7 more
Treatment Details
Interventions
- Ponsegromab (Monoclonal Antibodies)
Trial OverviewThe study tests different doses of Ponsegromab against a placebo in people with heart failure to see if it improves their symptoms. Participants are randomly assigned to receive either the drug or placebo via injections every four weeks without knowing which one they get. There's also an open-label part where everyone gets Ponsegromab without any placebos involved.
Participant Groups
11Treatment groups
Experimental Treatment
Placebo Group
Group I: Optional Cohort D: ponsegromab high doseExperimental Treatment1 Intervention
Participants will receive a high dose Q4W SC
Group II: Optional Cohort C: ponsegromab low doseExperimental Treatment1 Intervention
Participants will receive a low dose Q4W SC
Group III: Open-label, PK Cohort (Cohort B): ponsegromab medium doseExperimental Treatment1 Intervention
Participants will receive a medium dose Q4W SC
Group IV: Open-label, PK Cohort (Cohort B): ponsegromab low doseExperimental Treatment1 Intervention
Participants will receive a low dose Q4W SC
Group V: Open-label, PK Cohort (Cohort B): ponsegromab high doseExperimental Treatment1 Intervention
Participants will receive a high dose Q4W SC
Group VI: Main cohort (Cohort A): ponsegromab medium doseExperimental Treatment1 Intervention
Participants will receive a medium dose Q4W SC
Group VII: Main cohort (Cohort A): ponsegromab low doseExperimental Treatment1 Intervention
Participants will receive a low dose Q4W SC
Group VIII: Main cohort (Cohort A): ponsegromab high doseExperimental Treatment1 Intervention
Participants will receive a high dose Q4W SC
Group IX: Main cohort (Cohort A): placeboPlacebo Group1 Intervention
matched placebo
Group X: Optional Cohort C: placeboPlacebo Group1 Intervention
matched placebo
Group XI: Optional Cohort D: placeboPlacebo Group1 Intervention
matched placebo
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
South Oklahoma Heart Research, LLCOklahoma City, OK
Centre intégré de santé et de services sociaux du Bas Saint-Laurent- Hôpital régional de RimouskiRimouski, Canada
Centre Hospitalier de l'Université de MontréalMontréal, Canada
Institut de Cardiologie de MontrealMontreal, Canada
More Trial Locations
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Who Is Running the Clinical Trial?
PfizerLead Sponsor
The TIMI Study GroupCollaborator
Thrombolysis In Myocardial Infarction (TIMI)Collaborator
References
Population Pharmacokinetics and Pharmacodynamics of Vericiguat in Patients with Heart Failure and Reduced Ejection Fraction. [2022]Vericiguat, a stimulator of soluble guanylate cyclase, has been developed as a first-in-class therapy for worsening chronic heart failure in adults with left ventricular ejection fraction
Reappraisal on pharmacological and mechanical treatments of heart failure. [2020]Heart failure (HF) is a highly frequent disorder with considerable morbidity, hospitalization, and mortality; thus, it invariably places pressure on clinical and public health systems in the modern world. There have been notable advances in the definition, diagnosis, and treatment of HF, and newly developed agents and devices have been widely adopted in clinical practice. Here, this review first summarizes the current emerging therapeutic agents, including pharmacotherapy, device-based therapy, and the treatment of some common comorbidities, to improve the prognosis of HF patients. Then, we discuss and point out the commonalities and areas for improvement in current clinical studies of HF. Finally, we highlight the gaps in HF research. We are looking forward to a bright future with reduced morbidity and mortality from HF.
Vericiguat: The Fifth Harmony of Heart Failure with Reduced Ejection Fraction. [2023]Heart failure with reduced ejection fraction is a chronic and progressive syndrome that continues to be a substantial financial burden for health systems in Western countries. Despite remarkable advances in pharmacologic and device-based therapy over the last few years, patients with heart failure with reduced ejection fraction have a high residual risk of adverse outcomes, even when treated with optimal guideline-directed medical therapy and in a clinically stable state. Worsening heart failure episodes represent a critical event in the heart failure trajectory, carrying high residual risk at discharge and dismal short- or long-term prognosis. Recently, vericiguat, a soluble guanylate cyclase stimulator, has been proposed as a novel drug whose use is already associated with a reduction in heart failure-related hospitalizations in patients in guideline-directed medical therapy. In this review, we summarized the pathophysiology of the nitric oxide-soluble guanylate cyclase-cyclic guanosine monophosphate cascade in patients with heart failure with reduced ejection fraction, the pharmacology of vericiguat as well as the evidence regarding their use in patients with HFrEF. Finally, tips and tricks for its use in standard clinical practice are provided.
Emerging Pharmacologic Therapies for Heart Failure With Reduced Ejection Fraction. [2022]The global burden of heart failure has reached epidemic proportions with tremendous health and economic consequences. Sodium glucose cotransporter 2 inhibitors, vericiguat, and omecamtiv mecarbil are novel agents that promise to blunt the high residual risk of heart failure with reduced ejection fraction. We review the vast knowledge base that has rapidly materialized for these agents and is poised to shape the current and future trends and recommendations in heart failure pharmacotherapy.
Efficacy and safety of vericiguat in heart failure: a meta-analysis. [2023]This study aimed to investigate the safety and efficacy of vericiguat in patients with heart failure (HF).
Vericiguat in Patients with Heart Failure and Reduced Ejection Fraction. [2021]The effect of vericiguat, a novel oral soluble guanylate cyclase stimulator, in patients with heart failure and reduced ejection fraction who had recently been hospitalized or had received intravenous diuretic therapy is unclear.
The efficacy and safety of soluble guanylate cyclase stimulators in patients with heart failure: A systematic review and meta-analysis. [2022]Several randomized controlled trials (RCTs) have been investigated the benefits of soluble guanylate cyclase (sGC) stimulators in the treatment of heart failure, but a comprehensive evaluation is lacking. We performed a meta-analysis to evaluate the efficacy and safety of oral sGC stimulators (vericiguat and riociguat) in patients with heart failure.
Efficacy and Safety of Vericiguat for Treatment of Heart Failure: A Systematic Review. [2023]Heart failure is a growing global health concern with high mortality and morbidity. Beta-blockers, mineralocorticoid receptor antagonists, and angiotensin-converting-enzyme inhibitors are the treatments of choice for worsening clinical symptoms. In early 2021, the FDA approved a new oral soluble guanylate cyclase stimulator, Vericiguat, for the treatment of chronic heart failure. To evaluate the efficacy and safety of this approved drug, we conducted a systematic review of the available randomized controlled trials (RCTs). A literature search was conducted using PubMed, The Cochrane Library, and Clinicaltrials.gov from inception to June 6, 2022, without any language restriction. The systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The quality of the included studies was checked using the Cochrane Risk-of-Bias tool. After a thorough literature search, 7 studies met our pre-defined criteria and were therefore included in this review. Our review suggests that vericiguat was better in preventing all causes of death, cardiovascular death, and hospitalizations due to heart failure irrespective of the atrial fibrillation status of the patients and was even beneficial for patients with NT-proBNP levels up to 8000 pg/ml. The safety of the vericiguat, according to our review, is not up to the standards, especially with a higher dosage of vericiguat. Despite all of this, vericiguat can be a breakthrough in the treatment of heart failure as it has great potential to improve the disease severity.
Vericiguat in patients with heart failure and reduced ejection fraction. [2022]The effect of vericiguat, a novel oral soluble guanylate cyclase stimulator, in patients with heart failure and reduced ejection fraction who had recently been hospitalized or had received intravenous diuretic therapy is unclear.
Effect of vericiguat on left ventricular structure and function in patients with heart failure with reduced ejection fraction: The VICTORIA echocardiographic substudy. [2023]Vericiguat significantly reduced the primary composite outcome of heart failure (HF) hospitalization or cardiovascular death in the VICTORIA trial. It is unknown if these outcome benefits are related to reverse left ventricular (LV) remodelling with vericiguat in patients with HF with reduced ejection fraction (HFrEF). The aim of this study was to compare the effects of vericiguat versus placebo on LV structure and function after 8 months of therapy in patients with HFrEF.
Vericiguat: A Review in Chronic Heart Failure with Reduced Ejection Fraction. [2022]Vericiguat (Verquvo®) is the first oral soluble guanylate cyclase (sGC) stimulator to be approved for the treatment of adults with symptomatic, chronic heart failure with reduced ejection fraction (HFrEF). In the phase III VICTORIA trial, vericiguat added to standard of care (SOC) was associated with a significantly lower risk of the primary composite endpoint of death from cardiovascular (CV) causes or first hospitalization from heart failure (HHF) than placebo added to SOC in adults with chronic HFrEF. The risk of all-cause mortality or first HHF (secondary composite endpoint) and the total number of HHF were also statistically significantly reduced by vericiguat therapy. Vericiguat showed no benefit with respect to the primary endpoint in a subgroup of patients with grossly elevated N-terminal pro-brain natriuretic peptide levels. Vericiguat was generally well tolerated; the most common treatment-related adverse event (AE) was hypotension. AEs of special interest included symptomatic hypotension and syncope, which occurred with low incidences that were similar between treatment groups. Thus, vericiguat is an effective and generally well-tolerated treatment option in patients with symptomatic, chronic HFrEF who have experienced a recent worsening event, expanding the options currently available for chronic HFrEF management.
Vericiguat reduced a composite of CV death or HF hospitalization in patients with HF and reduced LVEF. [2020]Label="SOURCE CITATION">Armstrong PW, Pieske B, Anstrom KJ, et al. Vericiguat in patients with heart failure and reduced ejection fraction. N Engl J Med. 2020;382:1883-93. 32222134.