A Study of Ponsegromab in People With Heart Failure

Phase 2

Terminated

• Conditions: Heart Failure

• Registration Number: NCT05492500
• Lead Sponsor: Pfizer

Brief Summary

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 like the study medicine but does not contain the active medicine) to find out if the study medicine is better than the placebo (an injection that looks like the study medicine but does not contain the active medicine) for treatment of symptoms related to heart failure. Participants will not know which treatment group they are assigned to. Most participants in this study will receive the study medicine or placebo by shots under the skin every four weeks. People may be able to participate in this study if they have heart failure. Participants will take part in this study for about 9 months. During this time participants will visit the study clinic once a month.

A separate PK cohort within this clinical trial will receive open-label study medicine (Ponsegromab/PF-06946860) only. Participants in this open-label, PK cohort will not receive placebo. These participants will receive the study medicine by shots under the skin every four weeks. People may be able to participate in this study cohort if they also have heart failure. Participants will take part in the open-label, PK cohort for about 7 months.

Detailed Description

The primary purpose of this study is to assess the effect of repeated subcutaneous administration of ponsegromab (PF-06946860) compared to placebo on frequency, severity, and burden of symptoms as well as physical limitations in participants with heart failure and different ranges of circulating GDF-15 concentrations. The study will also assess the safety, tolerability, PK, PD, and immunogenicity of ponsegromab.

A separate, open-label, PK cohort, with more frequent PK and GDF-15 collection after single and multiple subcutaneous administration of ponsegromab (PF-06946860), will be enrolled at certain sites to facilitate a more comprehensive assessment of PK characteristics and PK/PD relationship for GDF-15 in participants with heart failure and elevated circulating GDF-15 concentrations.

Study Timeline

• Study First Submitted: 2022-07-25
• Study First Submitted QC: 2022-08-05
• Study First Posted: 2022-08-08
• Study Start: 2022-09-26
• Primary Completion: 2025-03-05
• Study Completion: 2025-03-05
• Status Verified: 2025-06
• Last Update Submitted: 2025-06-11
• Last Update Posted: 2025-06-13

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 455

Inclusion Criteria

• Male and female participants aged 18 years or older

  -. Clinical evidence of HF with each of the following criteria:

  1. LVEF <50% on most recent measurement, within 12 months of screening. Note: An assessment of LVEF in the prior 12 months is not required in situations where LVEF has been persistently <50% on prior assessments obtained at least 3 months apart (including the most recent measurement).
  2. NYHA class II-IV at screening.
  3. NT-proBNP ≥400 pg/mL at screening (Note: Does not apply to open-label, PK Cohort [Cohort B]).

• Serum GDF-15 concentration ≥2000 pg/mL at screening.

• Cohort D only: Serum GDF-15 concentration <2000 pg/mL at screening.

• KCCQ-23 CSS <75 at screening (Note: Does not apply to open-label, PK Cohort [Cohort B]).

• Evidence of cachexia or fatigue or functional impairment, as demonstrated by at least one of the following at screening (Note: Does not apply to open-label, PK Cohort [Cohort B]):

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

Exclusion Criteria

• Acute decompensated HF within 1 month prior to Screening Visit 1 or during the screening period.
• 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.

For the open-label, PK cohort (Cohort B) only: implantation of a cardiac resynchronization therapy device more than 1 month prior to randomization is permitted.

• History of heart transplantation, currently listed for heart transplant, current/planned mechanical circulatory support, or current/planned use of intravenous inotropes (eg, dobutamine, milrinone).
• Acute coronary syndrome within 1 month prior to randomization.
• Coronary revascularization (percutaneous coronary intervention or coronary artery bypass grafting) within 3 months prior to randomization or intent to undergo coronary revascularization during the trial.

For the open-label, PK cohort (Cohort B) only: coronary revascularization more than 1 month prior to randomization is permitted.

• Untreated indication for an implantable cardiac defibrillator or pacemaker to treat a cardiac rhythm abnormality (ie, tachyarrhythmia or bradyarrhythmia).
• Previous administration with an investigational product (drug or vaccine) within 30 days (or as determined by the local requirement) or 5 half lives (whichever is longer) preceding the first dose of study intervention used in this study. Treatment with an investigational biologic agent within 6 months or 5 half-lives (whichever is longer) of Day 1.
• Previous exposure to ponsegromab in a prior clinical study.
• Renal disease requiring ongoing dialysis.
• Cirrhosis with evidence of portal hypertension not due to HF, or the following LFT abnormalities at the time of screening, confirmed by a repeat test if deemed necessary: AST or ALT level ≥ 3 x ULN, or total bilirubin level ≥ 2 x ULN (unless history of Gilbert's syndrome).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Main cohort (Cohort A): Change from baseline in Kansas City Cardiomyopathy Questionnaire 23 Clinical Summary Score	baseline, 22 weeks	To compare the effect of high dose ponsegromab versus placebo, on heart failure disease-specific health status in participants with HF and elevated serum GDF-15 concentrations

Secondary Outcome Measures

Name	Time	Method
Main cohort (Cohort A): Change from baseline in Kansas City Cardiomyopathy Questionnaire 23 Overall Summary Score	baseline, 22 weeks	To compare the effect of ponsegromab versus placebo on HF disease-specific overall health status in participants with HF and elevated serum GDF-15 concentrations
Main cohort (Cohort A): Change from baseline in Kansas City Cardiomyopathy Questionnaire 23 Total Symptom Score	baseline, 22 weeks	To compare the effect of ponsegromab versus placebo on HF disease-specific overall health status in participants with HF and elevated serum GDF-15 concentrations
Main cohort (Cohort A): Change from baseline in Kansas City Cardiomyopathy Questionnaire 23 physical limitations domain	baseline, 22 weeks	To compare the effect of ponsegromab versus placebo on HF disease-specific overall health status in participants with HF and elevated serum GDF-15 concentrations
Main cohort (Cohort A): Responses as defined by a ≥5 point increase from baseline in Kansas City Cardiomyopathy Questionnaire 23 Clinical Summary Score	baseline, 22 weeks	To compare the effect of ponsegromab versus placebo on HF disease-specific health status in participants with HF and elevated serum GDF-15 concentrations
Main cohort (Cohort A): Responses as defined by a ≥5 point increase from baseline in Overall Summary Score	baseline, 22 weeks	To compare the effect of ponsegromab versus placebo on HF disease-specific health status in participants with HF and elevated serum GDF-15 concentrations
Main cohort (Cohort A): Responses as defined by a ≥5 point increase from baseline in Total Symptom Score	baseline, 22 weeks	To compare the effect of ponsegromab versus placebo on HF disease-specific health status in participants with HF and elevated serum GDF-15 concentrations
Main cohort (Cohort A): Responses as defined by a ≥5 point increase from baseline in physical limitation	baseline, 22 weeks	To compare the effect of ponsegromab versus placebo on HF disease-specific health status in participants with HF and elevated serum GDF-15 concentrations
Main cohort (Cohort A): Change from baseline in 6-Minute Walk Distance	baseline, 22 weeks	To compare the effect of ponsegromab versus placebo on the physical function of participants with HF and elevated serum GDF-15 concentrations
Main cohort (Cohort A): Change from baseline in PROMIS-Fatigue 7a which will be completed by study participants on an electronic device, so as to compare the effect of ponsegromab versus placebo on fatigue as reported by participants with HF	baseline, 22 weeks	To compare the effect of ponsegromab versus placebo on fatigue reported by participants with HF and elevated serum GDF-15 concentrations
Main cohort (Cohort A)/Cohort C/Cohort D: Incidence of treatment-emergent adverse events	32 weeks	To describe the safety and tolerability of ponsegromab in participants with HF
Main cohort (Cohort A)/Cohort C/Cohort D: Incidence of treatment-emergent serious adverse events	32 weeks	To describe the safety and tolerability of ponsegromab in participants with HF
Main cohort (Cohort A)/Cohort C/Cohort D: Incidence of abnormal laboratory results	32 weeks	To describe the safety and tolerability of ponsegromab in participants with HF
Main cohort (Cohort A)/Cohort C/Cohort D: Incidence of abnormal vital signs	32 weeks	To describe the safety and tolerability of ponsegromab in participants with HF
Open-Label, PK Cohort (Cohort B): Incidence of treatment-emergent adverse events	22 weeks	To describe the safety and tolerability of ponsegromab in participants with HF
Open-Label, PK Cohort (Cohort B): Incidence of treatment-emergent serious adverse events	22 weeks	To describe the safety and tolerability of ponsegromab in participants with HF
Open-Label, PK Cohort (Cohort B): Incidence of abnormal laboratory results	22 weeks	To describe the safety and tolerability of ponsegromab in participants with HF
Open-Label, PK Cohort (Cohort B): Incidence of abnormal vital signs	22 weeks	To describe the safety and tolerability of ponsegromab in participants with HF

Trial Locations

Locations (121)

Eastern shore Research Institute LLC; 🇺🇸 Fairhope, Alabama, United States

Keck Medical Center of USC; 🇺🇸 Los Angeles, California, United States

MedStar Washington Hospital Center; 🇺🇸 Washington, District of Columbia, United States

Emory University School of Medicine-Grady Campus; 🇺🇸 Atlanta, Georgia, United States

Chicago Medical Research; 🇺🇸 Hazel Crest, Illinois, United States

Reid Physician Associates; 🇺🇸 Richmond, Indiana, United States

Brigham and Women's Hospital; 🇺🇸 Boston, Massachusetts, United States

Henry Ford Hospital; 🇺🇸 Detroit, Michigan, United States

Traverse Heart & Vascular; 🇺🇸 Traverse City, Michigan, United States

M Health Fairview Clinics and Surgery Center; 🇺🇸 Minneapolis, Minnesota, United States

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