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A Study of Ponsegromab in People With Heart Failure

PHASE2RECRUITING

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.

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Study details:

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.

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Eligibility criteria

Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.

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).

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Eligibility

Age eligible for study : 18 and older

Healthy volunteers accepted : No

Gender eligible for study: All

Things to know

Study dates

Study start: 2022-09-26

Primary completion: 2026-03-02

Study completion finish: 2026-03-02

Study type

SUPPORTIVE_CARE

Phase

PHASE2

Trial ID

NCT05492500

Intervention or treatment

DRUG: Main cohort (Cohort A): Ponsegromab low dose

DRUG: Main cohort (Cohort A): Ponsegromab medium dose

DRUG: Main cohort (Cohort A): ponsegromab high dose

OTHER: Main cohort (Cohort A): Matched placebo

DRUG: Open-label, PK Cohort (Cohort B): ponsegromab low dose

DRUG: Open-label, PK Cohort (Cohort B): ponsegromab medium dose

DRUG: Open-label, PK Cohort (Cohort B): ponsegromab high dose

DRUG: Optional Cohort C: Ponsegromab low dose

OTHER: Optional Cohort C: Matched placebo

DRUG: Optional Cohort D: Ponsegromab high dose

OTHER: Optional Cohort D: Matched placebo

Conditions

• Heart Failure

Condition: Heart Failure
DRUG: Main cohort (Cohort A): Ponsegromab low dose and other drugs
Concord, New South Wales, Australia and more
Sponsor: Pfizer

You may be eligible to participate in this trial based on your search. Check eligibility by answering some questions.

Are you running this trial? If you're a clinic or sponsor, you can claim this study. Claim or learn more.

Find a site

Closest Location:

Concord Repatriation General Hospital

Research sites nearby

Select from list below to view details:

Concord Repatriation General Hospital
Concord, New South Wales, Australia
The Prince Charles Hospital
Chermside, Queensland, Australia
Gold Coast University Hospital
Southport, Queensland, Australia
Lyell McEwin Hospital
Elizabeth Vale, South Australia, Australia

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Main cohort (Cohort A): ponsegromab low dose Participants will receive a low dose Q4W SC	DRUG: Main cohort (Cohort A): Ponsegromab low dose Ponsegromab low dose subcutaneous injection
EXPERIMENTAL: Main cohort (Cohort A): ponsegromab medium dose Participants will receive a medium dose Q4W SC	DRUG: Main cohort (Cohort A): Ponsegromab medium dose Ponsegromab medium dose subcutaneous injection
EXPERIMENTAL: Main cohort (Cohort A): ponsegromab high dose Participants will receive a high dose Q4W SC	DRUG: Main cohort (Cohort A): ponsegromab high dose Ponsegromab high dose subcutaneous injection
PLACEBO_COMPARATOR: Main cohort (Cohort A): placebo matched placebo	OTHER: Main cohort (Cohort A): Matched placebo Matched placebo subcutaneous injection
EXPERIMENTAL: Open-label, PK Cohort (Cohort B): ponsegromab low dose Participants will receive a low dose Q4W SC	DRUG: Open-label, PK Cohort (Cohort B): ponsegromab low dose ponsegromab low dose subcutaneous injection
EXPERIMENTAL: Open-label, PK Cohort (Cohort B): ponsegromab medium dose Participants will receive a medium dose Q4W SC	DRUG: Open-label, PK Cohort (Cohort B): ponsegromab medium dose Ponsegromab medium dose subcutaneous injection
EXPERIMENTAL: Open-label, PK Cohort (Cohort B): ponsegromab high dose Participants will receive a high dose Q4W SC	DRUG: Open-label, PK Cohort (Cohort B): ponsegromab high dose Ponsegromab high dose subcutaneous injection
EXPERIMENTAL: Optional Cohort C: ponsegromab low dose Participants will receive a low dose Q4W SC	DRUG: Optional Cohort C: Ponsegromab low dose Ponsegromab low dose subcutaneous injection
PLACEBO_COMPARATOR: Optional Cohort C: placebo matched placebo	OTHER: Optional Cohort C: Matched placebo Matched placebo subcutaneous injection
EXPERIMENTAL: Optional Cohort D: ponsegromab high dose Participants will receive a high dose Q4W SC	DRUG: Optional Cohort D: Ponsegromab high dose Ponsegromab high dose subcutaneous injection
PLACEBO_COMPARATOR: Optional Cohort D: placebo matched placebo	OTHER: Optional Cohort D: Matched placebo Matched placebo subcutaneous injection

What is the study measuring?

Primary outcome

Primary Outcome Measure	Primary Outcome Description	Primary Outcome Time Frame
Main cohort (Cohort A): Change from baseline in Kansas City Cardiomyopathy Questionnaire 23 Clinical Summary Score	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	baseline, 22 weeks

Secondary outcome

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

Frequently Asked Questions

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References

Clinical Trials Gov: A Study of Ponsegromab in People With Heart Failure