DRUG
Main cohort (Cohort A): Ponsegromab low dose
Ponsegromab low dose subcutaneous injection
A Study of Ponsegromab in People With Heart Failure
Status
Terminated
Phase
Phase 2
Enrollment
455
Locations
122
Results
Posted
Publications
0
Study summary
What the protocol is testing.
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.
Full 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.
Interventions
Treatment arms and agents.
DRUG
Main cohort (Cohort A): Ponsegromab medium dose
Ponsegromab medium dose subcutaneous injection
DRUG
Main cohort (Cohort A): ponsegromab high dose
Ponsegromab high dose subcutaneous injection
OTHER
Main cohort (Cohort A): Matched placebo
Matched placebo subcutaneous injection
DRUG
Open-label, PK Cohort (Cohort B): ponsegromab low dose
ponsegromab low dose subcutaneous injection
DRUG
Open-label, PK Cohort (Cohort B): ponsegromab medium dose
Ponsegromab medium dose subcutaneous injection
DRUG
Open-label, PK Cohort (Cohort B): ponsegromab high dose
Ponsegromab high dose subcutaneous injection
DRUG
Optional Cohort C: Ponsegromab low dose
Ponsegromab low dose subcutaneous injection
OTHER
Optional Cohort C: Matched placebo
Matched placebo subcutaneous injection
DRUG
Optional Cohort D: Ponsegromab high dose
Ponsegromab high dose subcutaneous injection
OTHER
Optional Cohort D: Matched placebo
Matched placebo subcutaneous injection
Timeline
From registration to results.
First posted
Aug 8, 2022
Study start
Sep 26, 2022
Primary completion
Mar 5, 2025
Study completion
Mar 5, 2025
Results posted
Mar 18, 2026
Registry updated
Mar 18, 2026
Outcomes
What the study measures.
Primary outcomes
Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ)-23 - Clinical Summary Score (CSS) at Week 22: Cohort A, Ponsegromab 300 mg Versus Placebo
Time frame · Baseline [the last measurement on study Day 1], Week 22
KCCQ is a self-reported 23-item questionnaire that assessed health related quality of life (HRQL) in participants with heart failure (HF) over the past 2 weeks. KCCQ quantifies 7 domains: physical limitations (6 items), symptom stability (1 item), symptom frequency (4 items), symptom burden (3 items), self-efficacy (2 items), quality of life (3 items) and social limitations (4 items). Scores were generated for each domain and scaled from 0 (worst status) to 100 (best possible status). KCCQ total symptom score (TSS): mean of domains- symptom frequency and symptom burden; and was transformed to a single score which ranged from 0 (worst) to 100 (best possible status). KCCQ-23-CSS: mean of the TSS and physical limitation domain score; and was transformed to a single score which ranged from 0 (worst) to 100 (best possible status), where higher KCCQ-23-CSS signified better health status.
Secondary outcomes
Change From Baseline in KCCQ-23 CSS at Week 22: Cohort A
Time frame · Baseline [the last measurement on study Day 1], Week 22
KCCQ is a self-reported 23-item questionnaire that assessed HRQL in participants with HF over the past 2 weeks. KCCQ quantifies 7 domains: physical limitations (6 items), symptom stability (1 item), symptom frequency (4 items), symptom burden (3 items), self-efficacy (2 items), quality of life (3 items) and social limitations (4 items). Scores were generated for each domain and scaled from 0 (worst status) to 100 (best possible status). KCCQ TSS: mean of domains- symptom frequency and symptom burden; and was transformed to a single score which ranged from 0 (worst) to 100 (best possible status). KCCQ-23-CSS: mean of the TSS and physical limitation domain score; and was transformed to a single score which ranged from 0 (worst) to 100 (best possible status), where higher KCCQ-23-CSS signified better health status.
Change From Baseline in KCCQ-23-Overall Summary Score (OSS) at Week 22: Cohort A, Ponsegromab 300 mg Versus Placebo
Time frame · Baseline [the last measurement on study Day 1], Week 22
KCCQ is a self-reported 23-item questionnaire that assessed HRQL in participants with HF over the past 2 weeks. KCCQ quantifies 7 domains: physical limitations (6 items), symptom stability (1 item), symptom frequency (4 items), symptom burden (3 items), self-efficacy (2 items), quality of life (3 items) and social limitations (4 items). Scores were generated for each domain and scaled from 0 (worst status) to 100 (best possible status). KCCQ-23-OSS: mean of domain scores- physical limitation, quality of life, social limitation and TSS (mean of symptom frequency and symptom burden); and was transformed to a single score which ranged from 0 (worst) to 100 (best possible status), where higher KCCQ-23-OSS signified better health status.
Change From Baseline in KCCQ-23 OSS at Week 22: Cohort A
Time frame · Baseline [the last measurement on study Day 1], Week 22
KCCQ is a self-reported 23-item questionnaire that assessed HRQL in participants with HF over the past 2 weeks. KCCQ quantifies 7 domains: physical limitations (6 items), symptom stability (1 item), symptom frequency (4 items), symptom burden (3 items), self-efficacy (2 items), quality of life (3 items) and social limitations (4 items). Scores were generated for each domain and scaled from 0 (worst status) to 100 (best possible status). KCCQ-23-OSS: mean of domain scores- physical limitation, quality of life, social limitation and TSS (mean of symptom frequency and symptom burden); and was transformed to a single score which ranged from 0 (worst) to 100 (best possible status), where higher KCCQ-23-OSS signified better health status.
Change From Baseline in KCCQ-23-TSS at Week 22: Cohort A, Ponsegromab 300 mg Versus Placebo
Time frame · Baseline [the last measurement on study Day 1], Week 22
KCCQ is a self-reported 23-item questionnaire that assessed HRQL in participants with HF over the past 2 weeks. KCCQ quantifies 7 domains: physical limitations (6 items), symptom stability (1 item), symptom frequency (4 items), symptom burden (3 items), self-efficacy (2 items), quality of life (3 items) and social limitations (4 items). Scores were generated for each domain and scaled from 0 (worst status) to 100 (best possible status). KCCQ-23-TSS: mean of domains- symptom frequency and symptom burden; and was transformed to a single score which ranged from 0 (worst) to 100 (best possible status), where higher KCCQ-23-TSS signified better health status.
Change From Baseline in KCCQ-23 TSS at Week 22: Cohort A
Time frame · Baseline [the last measurement on study Day 1], Week 22
KCCQ is a self-reported 23-item questionnaire that assessed HRQL in participants with HF over the past 2 weeks. KCCQ quantifies 7 domains: physical limitations (6 items), symptom stability (1 item), symptom frequency (4 items), symptom burden (3 items), self-efficacy (2 items), quality of life (3 items) and social limitations (4 items). Scores were generated for each domain and scaled from 0 (worst status) to 100 (best possible status). KCCQ-23-TSS: mean of domains- symptom frequency and symptom burden; and was transformed to a single score which ranged from 0 (worst) to 100 (best possible status), where higher KCCQ-23-TSS signified better health status.
Change From Baseline in KCCQ-23 Physical Limitation Score at Week 22: Cohort A, Ponsegromab 300 mg Versus Placebo
Time frame · Baseline [the last measurement on study Day 1], Week 22
KCCQ is a self-reported 23-item questionnaire that assessed HRQL in participants with HF over the past 2 weeks. KCCQ quantifies 7 domains: physical limitations (6 items), symptom stability (1 item), symptom frequency (4 items), symptom burden (3 items), self-efficacy (2 items), quality of life (3 items) and social limitations (4 items). Scores were generated for each domain and scaled from 0 (worst status) to 100 (best possible status). KCCQ-23 physical limitation score scaled from 0 (worst status) to 100 (best possible status), where higher scores signified better health status.
Change From Baseline in KCCQ-23 Physical Limitation Score at Week 22: Cohort A
Time frame · Baseline [the last measurement on study Day 1], Week 22
KCCQ is a self-reported 23-item questionnaire that assessed HRQL in participants with HF over the past 2 weeks. KCCQ quantifies 7 domains: physical limitations (6 items), symptom stability (1 item), symptom frequency (4 items), symptom burden (3 items), self-efficacy (2 items), quality of life (3 items) and social limitations (4 items). Scores were generated for each domain and scaled from 0 (worst status) to 100 (best possible status). KCCQ-23 physical limitation score scaled from 0 (worst status) to 100 (best possible status), where higher scores signified better health status.
Percentage of Participants With >= 5-Point Increase From Baseline in KCCQ-23-CSS at Week 22: Cohort A, Ponsegromab 300 mg Versus Placebo
Time frame · Week 22
KCCQ is a self-reported 23-item questionnaire that assessed HRQL in participants with HF over the past 2 weeks. KCCQ quantifies 7 domains: physical limitations (6 items), symptom stability (1 item), symptom frequency (4 items), symptom burden (3 items), self-efficacy (2 items), quality of life (3 items) and social limitations (4 items). Scores were generated for each domain and scaled from 0 (worst status) to 100 (best possible status). KCCQ TSS: mean of domains- symptom frequency and symptom burden; and was transformed to a single score which ranged from 0 (worst) to 100 (best possible status). KCCQ-23-CSS: mean of the TSS and physical limitation domain score; and was transformed to a single score which ranged from 0 (worst) to 100 (best possible status), where higher KCCQ-23-CSS signified better health status.
Percentage of Participants With >= 5-Point Increase From Baseline in KCCQ-23 CSS Score at Week 22: Cohort A
Time frame · Week 22
KCCQ is a self-reported 23-item questionnaire that assessed HRQL in participants with HF over the past 2 weeks. KCCQ quantifies 7 domains: physical limitations (6 items), symptom stability (1 item), symptom frequency (4 items), symptom burden (3 items), self-efficacy (2 items), quality of life (3 items) and social limitations (4 items). Scores were generated for each domain and scaled from 0 (worst status) to 100 (best possible status). KCCQ TSS: mean of domains- symptom frequency and symptom burden; and was transformed to a single score which ranged from 0 (worst) to 100 (best possible status). KCCQ-23-CSS: mean of the TSS and physical limitation domain score; and was transformed to a single score which ranged from 0 (worst) to 100 (best possible status), where higher KCCQ-23-CSS signified better health status.
Percentage of Participants With >= 5-Point Increase From Baseline in KCCQ-23 OSS Score at Week 22: Cohort A, Ponsegromab 300 mg Versus Placebo
Time frame · Week 22
KCCQ is a self-reported 23-item questionnaire that assessed HRQL in participants with HF over the past 2 weeks. KCCQ quantifies 7 domains: physical limitations (6 items), symptom stability (1 item), symptom frequency (4 items), symptom burden (3 items), self-efficacy (2 items), quality of life (3 items) and social limitations (4 items). Scores were generated for each domain and scaled from 0 (worst status) to 100 (best possible status). KCCQ-23-OSS: mean of domain scores- physical limitation, quality of life, social limitation and TSS (mean of symptom frequency and symptom burden); and was transformed to a single score which ranged from 0 (worst) to 100 (best possible status), where higher KCCQ-23-OSS signified better health status.
Eligibility
Who can take part.
- Minimum age
- 18 Years
- Maximum age
- Not reported
- Sex
- ALL
- Healthy volunteers
- No
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 locations
122 registered sites.
Australia · Canada · China · Czechia · Germany · Hungary · Japan · Poland · Spain · United Kingdom · United States. Showing up to 24 locations stored in the fast local snapshot.
Eastern shore Research Institute LLC
Fairhope, Alabama, United States
Keck Medical Center of USC
Los Angeles, California, United States
MedStar Washington Hospital Center
Washington D.C., 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
M Health Fairview University of Minnesota Investigational Drug Services
Minneapolis, Minnesota, United States
M Health Fairview University of Minnesota Medical Center-East Bank
Minneapolis, Minnesota, United States
University of Minnesota/Lillehei Clinical Research Unit
Minneapolis, Minnesota, United States
Saint Luke's Hospital of Kansas City
Kansas City, Missouri, United States
Washington University in St. Louis Center for Outpatient Health (COH)
St Louis, Missouri, United States
Washington University in St. Louis Center for Advanced Medicine (CAM)
St Louis, Missouri, United States
Washington University School of Medicine
St Louis, Missouri, United States
Holy Name Medical Center
Teaneck, New Jersey, United States
University of North Carolina Medical Center
Chapel Hill, North Carolina, United States
Clinical and Translational Research Center
Chapel Hill, North Carolina, United States
South Oklahoma Heart Research, LLC
Oklahoma City, Oklahoma, United States
Texas Health Heart & Vascular Specialist (THHVS) #18760
Dallas, Texas, United States
Concord Repatriation General Hospital
Concord, New South Wales, Australia
Core Research Group
Brisbane, Queensland, Australia
Publications
Results and literature.
No PMID-linked publications were present in this registry snapshot.
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