Ponsegromab for Heart Failure

(GARDEN TIMI 74 Trial)

No longer recruiting at 155 trial locations

Overseen By Pfizer CT.gov Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Pfizer

Disqualifiers: Heart transplant, Renal dialysis, Cirrhosis, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 22 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called Ponsegromab to determine its effectiveness in alleviating heart failure symptoms. Participants receive injections under the skin every four weeks, with some receiving a placebo (a look-alike injection with no active medicine) for comparison. Another group will receive only Ponsegromab. Individuals with heart failure who experience significant fatigue or unintentional weight loss may be suitable for this study. Participants must visit the study clinic once a month for about 7 to 9 months. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

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.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that ponsegromab has been tested in people for other conditions, such as cancer-related weight loss. In these studies, ponsegromab improved body weight and muscle mass, suggesting it was generally well-tolerated. However, detailed safety information for heart failure remains limited.

As this treatment is in the middle phase of clinical trials, it has demonstrated some safety in humans, but further study is needed to ensure its safety for people with heart failure. Trial participants will help gather more specific information about any side effects or adverse events related to ponsegromab. ^{1 2 3 4 5}

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

Ponsegromab is unique because it targets heart failure by potentially modifying the disease process rather than just managing symptoms. Most treatments for heart failure, like ACE inhibitors or beta-blockers, work by managing symptoms and supporting heart function. Ponsegromab, however, may offer a novel approach by directly interacting with specific biological pathways involved in the disease. Researchers are excited because this could lead to more effective management of heart failure and improve patient outcomes beyond what current treatments offer.

What evidence suggests that Ponsegromab might be an effective treatment for heart failure?

Research has shown that ponsegromab may alleviate heart failure symptoms. In earlier studies, participants who took ponsegromab experienced improvements in body weight, muscle mass, and overall quality of life. These improvements suggest enhanced mobility and function, crucial for heart failure patients. In this trial, participants will receive varying doses of ponsegromab or a placebo. Ponsegromab targets a protein called GDF-15, often elevated in individuals with heart issues. By reducing the effects of this protein, ponsegromab might improve the condition of heart failure patients. ^{1 2 5 6 7}

Who Is on the Research Team?

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Are You a Good Fit for This Trial?

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 experience fatigue at least 3 times a week and it significantly bothers me.

I have experienced significant weight loss, fatigue, or physical limitations recently.

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.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive subcutaneous administration of ponsegromab or placebo every four weeks

22 weeks

Monthly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension (optional)

Participants in the PK cohort receive open-label ponsegromab for further assessment

7 months

Monthly visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Ponsegromab

Trial Overview The 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.

How Is the Trial Designed?

Group I: Optional Cohort D: ponsegromab high dose Experimental Treatment 1 Intervention

Participants will receive a high dose Q4W SC

Group II: Optional Cohort C: ponsegromab low dose Experimental Treatment 1 Intervention

Participants will receive a low dose Q4W SC

Group III: Open-label, PK Cohort (Cohort B): ponsegromab medium dose Experimental Treatment 1 Intervention

Participants will receive a medium dose Q4W SC

Group IV: Open-label, PK Cohort (Cohort B): ponsegromab low dose Experimental Treatment 1 Intervention

Participants will receive a low dose Q4W SC

Group V: Open-label, PK Cohort (Cohort B): ponsegromab high dose Experimental Treatment 1 Intervention

Participants will receive a high dose Q4W SC

Group VI: Main cohort (Cohort A): ponsegromab medium dose Experimental Treatment 1 Intervention

Participants will receive a medium dose Q4W SC

Group VII: Main cohort (Cohort A): ponsegromab low dose Experimental Treatment 1 Intervention

Participants will receive a low dose Q4W SC

Group VIII: Main cohort (Cohort A): ponsegromab high dose Experimental Treatment 1 Intervention

Participants will receive a high dose Q4W SC

Group IX: Main cohort (Cohort A): placebo Placebo Group 1 Intervention

matched placebo

Group X: Optional Cohort C: placebo Placebo Group 1 Intervention

matched placebo

Group XI: Optional Cohort D: placebo Placebo Group 1 Intervention

matched placebo

Who Is Running the Clinical Trial?

Pfizer

Lead Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

The TIMI Study Group

Collaborator

Trials

22

Recruited

129,000+

Thrombolysis In Myocardial Infarction (TIMI)

Collaborator

Trials

1

Recruited

780+

Published Research Related to This Trial

In a phase 3 trial involving 5050 patients with heart failure and reduced ejection fraction, vericiguat significantly reduced the risk of death from cardiovascular causes or hospitalization for heart failure compared to placebo, with a hazard ratio of 0.90.

The safety profile of vericiguat was comparable to placebo, with similar rates of symptomatic hypotension and syncope, indicating that it is a safe option for high-risk heart failure patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vericiguat in Patients with Heart Failure and Reduced Ejection Fraction. Armstrong, PW., Pieske, B., Anstrom, KJ., et al.[2021]

Vericiguat was found to be ineffective in reducing cardiovascular deaths or hospitalizations related to heart failure, based on a meta-analysis of four studies involving 6705 patients.

The study showed no significant difference in adverse effects between patients taking vericiguat and those on placebo, suggesting that it may be safe but not effective for heart failure treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of vericiguat in heart failure: a meta-analysis. Ma, J., Guo, S., Jiang, H., et al.[2023]

Vericiguat, a newly approved oral medication for chronic heart failure, has shown efficacy in reducing all-cause mortality, cardiovascular deaths, and hospitalizations related to heart failure across various patient profiles, including those with high NT-proBNP levels.

While vericiguat demonstrates significant benefits in managing heart failure, concerns about its safety profile, particularly at higher dosages, suggest that careful monitoring is necessary during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Vericiguat for Treatment of Heart Failure: A Systematic Review. Shaikh, TG., Jawed, S., Rahmat, ZS., et al.[2023]

In the VICTORIA trial, vericiguat showed a significant reduction in heart failure hospitalizations or cardiovascular death, but the study found that both vericiguat and placebo led to similar improvements in left ventricular (LV) structure and function after 8 months, indicating that the benefits of vericiguat may not be solely due to reverse LV remodeling.

The study included 419 patients with heart failure with reduced ejection fraction (HFrEF) and demonstrated a trend towards a lower rate of the primary composite endpoint in the vericiguat group compared to placebo, suggesting potential clinical benefits that warrant further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of vericiguat on left ventricular structure and function in patients with heart failure with reduced ejection fraction: The VICTORIA echocardiographic substudy. Pieske, B., Pieske-Kraigher, E., Lam, CSP., et al.[2023]

Vericiguat, a new drug that stimulates soluble guanylate cyclase, has been shown to reduce hospitalizations related to heart failure in patients already receiving guideline-directed medical therapy, indicating its efficacy in managing heart failure with reduced ejection fraction (HFrEF).

Despite advancements in treatment, patients with HFrEF still face a high risk of adverse outcomes, especially after worsening heart failure episodes, highlighting the need for additional therapeutic options like vericiguat to improve patient prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vericiguat: The Fifth Harmony of Heart Failure with Reduced Ejection Fraction. Falco, L., Brescia, B., Catapano, D., et al.[2023]

Sodium glucose cotransporter 2 inhibitors, vericiguat, and omecamtiv mecarbil are promising new treatments for heart failure with reduced ejection fraction, addressing the significant health risks associated with this condition.

These novel agents are expected to significantly impact heart failure management and treatment guidelines, as they target the high residual risk that remains despite current therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emerging Pharmacologic Therapies for Heart Failure With Reduced Ejection Fraction. Chaudhary, AG., Alreefi, FM., Aziz, MA.[2022]

Oral soluble guanylate cyclase (sGC) stimulators, specifically riociguat and vericiguat, showed no significant impact on mortality in heart failure patients but improved quality of life as measured by the EQ-5D index.

Riociguat was effective in significantly reducing NT-proBNP levels, indicating a potential benefit in heart failure management, while both sGC stimulators demonstrated good safety profiles with no notable increase in serious adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy and safety of soluble guanylate cyclase stimulators in patients with heart failure: A systematic review and meta-analysis. Zheng, X., Zheng, W., Xiong, B., et al.[2022]

In a phase 3 trial involving 5,050 patients with heart failure and reduced ejection fraction, vericiguat significantly reduced the risk of death from cardiovascular causes or hospitalization for heart failure compared to placebo, with a primary outcome event occurring in 35.5% of the vericiguat group versus 38.5% in the placebo group.

The study also found that while symptomatic hypotension and syncope were slightly more common in the vericiguat group, the overall safety profile was acceptable, indicating that vericiguat is an effective treatment option for high-risk heart failure patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vericiguat in patients with heart failure and reduced ejection fraction. Špinar, J., Špinarová, L., Vítovec, J.[2022]

Vericiguat was tested in a study involving patients with heart failure and reduced ejection fraction, showing significant efficacy in improving clinical outcomes compared to placebo.

The results suggest that vericiguat can be a beneficial treatment option for patients with this type of heart failure, potentially enhancing their quality of life and reducing hospitalizations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vericiguat reduced a composite of CV death or HF hospitalization in patients with HF and reduced LVEF. Averbuch, T., Van Spall, HGC.[2020]

Vericiguat, a new treatment for worsening chronic heart failure, has predictable pharmacokinetics and does not cause long-term changes in blood pressure, making it a safe option for patients with left ventricular ejection fraction < 45%.

The drug effectively reduces levels of NT-proBNP, a marker of heart failure severity, in an exposure-dependent manner, indicating its potential efficacy when combined with standard medical therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Population Pharmacokinetics and Pharmacodynamics of Vericiguat in Patients with Heart Failure and Reduced Ejection Fraction. Ruehs, H., Klein, D., Frei, M., et al.[2022]

In the phase III VICTORIA trial, vericiguat significantly reduced the risk of death from cardiovascular causes or first hospitalization for heart failure compared to placebo in adults with chronic heart failure with reduced ejection fraction (HFrEF).

Vericiguat was generally well tolerated, with hypotension being the most common treatment-related adverse event, indicating it is a safe and effective option for managing chronic HFrEF, especially after recent worsening events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vericiguat: A Review in Chronic Heart Failure with Reduced Ejection Fraction. Kang, C., Lamb, YN.[2022]

Recent advances in heart failure (HF) treatment include new medications and devices that have been integrated into clinical practice, aiming to improve patient outcomes and reduce hospitalizations.

The review identifies common issues in current HF clinical studies and emphasizes the need for further research to address existing gaps, ultimately striving for better management of HF and decreased morbidity and mortality.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reappraisal on pharmacological and mechanical treatments of heart failure. Liang, B., Zhao, YX., Zhang, XX., et al.[2020]

Citations

1. pfizer.com pfizer.com/news/press-release/press-release-detail/pfizer-presents-positive-data-phase-2-study-ponsegromab

Pfizer Presents Positive Data from Phase 2 Study of ... This study showed us those who received ponsegromab had improvement in body weight, muscle mass, quality of life, and physical function.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05492500

A Study of Ponsegromab in People With Heart Failure The primary purpose of this clinical trial is to compare the effects of study medicine (Ponsegromab/PF-06946860) with a placebo (an injection that looks ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10831332/

A Phase Ib First-In-Patient Study Assessing the Safety ... This first-in-patient (phase Ib), 24-week study assessed use of ponsegromab, a mAb against GDF-15, in adults with advanced cancer, cachexia, and elevated GDF- ...

4. assaygenie.com assaygenie.com/blog/ponsegromab-a-breakthrough-in-heart-failure-and-cachexia-research/?srsltid=AfmBOoq7lDz6whxxFTgS8oe3lYbThGvuSXOGN9CKYYvPjpq_gwtNZ9b0

A Breakthrough in Heart Failure and Cachexia Research By mitigating the effects of cachexia, Ponsegromab has the potential to improve quality of life and survival outcomes in patients with chronic ...

5. withpower.com withpower.com/trial/phase-2-heart-failure-8-2022-e3096

Ponsegromab for Heart Failure (GARDEN TIMI 74 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.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11154777/

Phase 2 study of the efficacy and safety of ponsegromab in ... The primary objective of this phase 2 study is to assess the effect of ponsegromab on body weight in patients with cancer, cachexia and elevated GDF‐15 ...

7. ctv.veeva.com ctv.veeva.com/study/a-study-of-ponsegromab-in-people-with-heart-failure

A Study of Ponsegromab in People With Heart Failure The primary purpose of this clinical trial is to compare the effects of study medicine (Ponsegromab/PF-06946860) with a placebo.