What is the mechanism of action of this treatment?

Common treatments for heart failure, such as beta-blockers, ACE inhibitors, ARBs, and diuretics, work by reducing the heart's workload, improving cardiac output, and managing symptoms like fluid retention. These treatments help to alleviate the strain on the heart and improve overall cardiac function. Ponsegromab (PF-06946860), currently under study, may target specific pathways to enhance cardiac function, potentially by modulating inflammatory or metabolic processes. This is important for heart failure patients as it could offer a new mechanism to improve heart function and manage symptoms more effectively.

What side effects are associated with this type of intervention?

Common treatments for heart failure, such as endothelin antagonists (e.g., bosentan and macitentan) and PDE-5 inhibitors (e.g., sildenafil), have shown various side effects. Endothelin antagonists can cause fluid retention, peripheral edema, and weight gain, leading to increased hospitalization risk. PDE-5 inhibitors may improve exercise capacity and hemodynamic variables but have not consistently shown clinical benefits in larger trials. Additionally, treatments like intravenous prostacyclin (epoprostenol) have been associated with decreased survival in some studies. These side effects highlight the importance of closely monitoring patients undergoing heart failure treatments.

What prior FDA approvals exist?

Several drugs have been approved by the FDA for the treatment of heart failure, focusing on improving cardiac function and related pathways. These include beta-blockers like carvedilol and metoprolol, which reduce heart rate and blood pressure, and ACE inhibitors such as enalapril and lisinopril, which help relax blood vessels. Additionally, angiotensin II receptor blockers (ARBs) like losartan and valsartan are used to lower blood pressure and reduce strain on the heart. More recently, neprilysin inhibitors combined with ARBs, such as sacubitril/valsartan, have been approved to enhance natriuretic peptides' effects, improving heart function and outcomes in heart failure patients.

What other types of research exist?

One promising alternative to Ponsegromab for heart failure patients is the REG2 anticoagulation system, which includes pegnivacogin, a factor IXa inhibitor. This system has been studied for its safety, tolerability, and pharmacokinetic and pharmacodynamic responses. Another potential option is PB2452, a monoclonal antibody fragment developed as a ticagrelor reversal agent, which has shown efficacy in reversing the antiplatelet effects of ticagrelor and could be beneficial in managing heart failure patients with concurrent antiplatelet therapy needs.

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Monoclonal Antibodies

Ponsegromab for Heart Failure (GARDEN TIMI 74 Trial)

Phase 2

Recruiting

Research Sponsored by Pfizer

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Evidence of cachexia or fatigue or functional impairment, as demonstrated by at least one of the following: Non-edematous unintentional weight loss ≥5% in the last 6 months or current BMI <20 kg/m2, associated with subjective fatigue or anorexia; or Fatigue at least 3 times per week AND at least moderately bothersome fatigue in the past 2 weeks; or A score of <60 on the Physical Limitations Domain of the KCCQ 23 administered at screening.

Fatigue at least 3 times per week AND at least moderately bothersome fatigue in the past 2 weeks

Must not have

Implantation of a cardiac resynchronization therapy device or valve repair or replacement within 3 months prior to randomization or intent to do so during the trial

Cirrhosis with evidence of portal hypertension not due to HF or specific LFT abnormalities at the time of screening

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 32 weeks

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

While specific side effects for Ponsegromab aren't listed here, common side effects from medications like this can include reactions at the injection site, nausea, headaches, and potential allergic responses. The exact side effects will be monitored throughout the trial.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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

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

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I have moderate to severe heart condition symptoms.

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I've lost more than 5% of my weight without trying in the last 6 months or my BMI is below 20, and I feel tired or have little appetite.

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I am experiencing significant weight loss, fatigue, or difficulty performing daily tasks.

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I have been diagnosed with heart failure.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have had or plan to have heart device surgery or valve repair/replacement recently.

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I have cirrhosis with signs of increased blood pressure in the liver not caused by heart failure.

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I have had or plan to have a procedure to improve blood flow to my heart soon.

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I am on dialysis for kidney disease.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 32 weeks

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~32 weeks

This trial's timeline: 3 weeks for screening, Varies for treatment, and 32 weeks for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Main cohort (Cohort A): Change from baseline in Kansas City Cardiomyopathy Questionnaire 23 Clinical Summary Score

Secondary study objectives

Main cohort (Cohort A)/Cohort C/Cohort D: Incidence of abnormal laboratory results

Main cohort (Cohort A)/Cohort C/Cohort D: Incidence of abnormal vital signs

Main cohort (Cohort A)/Cohort C/Cohort D: Incidence of treatment-emergent adverse events

+14 more

Trial Design

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

0 / 10Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for heart failure, such as beta-blockers, ACE inhibitors, ARBs, and diuretics, work by reducing the heart's workload, improving cardiac output, and managing symptoms like fluid retention. These treatments help to alleviate the strain on the heart and improve overall cardiac function. Ponsegromab (PF-06946860), currently under study, may target specific pathways to enhance cardiac function, potentially by modulating inflammatory or metabolic processes. This is important for heart failure patients as it could offer a new mechanism to improve heart function and manage symptoms more effectively.

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