Heart FailurePhase 2GARDEN TIMI 74NCT05492500
A Study of Ponsegromab in People With Heart Failure
A Phase 2 study testing Main cohort (Cohort A): Ponsegromab low dose, Main cohort (Cohort A): Ponsegromab medium dose and Main cohort (Cohort A): ponsegromab high dose in people with Heart Failure, run by Pfizer at 122 sites in 11 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Failure
- What is being tested?
- Main cohort (Cohort A): Ponsegromab low dose, Main cohort (Cohort A): Ponsegromab medium dose and Main cohort (Cohort A): ponsegromab high dose
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 455 participants
- Where
- 122 sitesin 11 countries
- Study dates
- 26 Sep 2022to 5 Mar 2025
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male and female participants aged 18 years or older
- -. Clinical evidence of HF with each of the following criteria:
- 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).
- NYHA class II-IV at screening.
- 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.
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- 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]):
- 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 based on the KCCQ-23 administered at screening; or
- A score of <60 on the Physical Limitations Domain of the KCCQ 23 administered at screening.
Who cannot join
- 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.
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- 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).
Trial locations and contacts
122 sites in 11 countries.
122 sites in 11 countries
United States22 sites
Emory University School of Medicine-Grady Campus
Atlanta, Georgia, 30303
Brigham and Women's Hospital
Boston, Massachusetts, 02115
University of North Carolina Medical Center
Chapel Hill, North Carolina, 27514
Clinical and Translational Research Center
Chapel Hill, North Carolina, 27599
Texas Health Heart & Vascular Specialist (THHVS) #18760
Dallas, Texas, 75231
Henry Ford Hospital
Detroit, Michigan, 48202
Eastern shore Research Institute LLC
Fairhope, Alabama, 36532
Chicago Medical Research
Hazel Crest, Illinois, 60429
Saint Luke's Hospital of Kansas City
Kansas City, Missouri, 64111
Keck Medical Center of USC
Los Angeles, California, 90033
M Health Fairview Clinics and Surgery Center
Minneapolis, Minnesota, 55455
M Health Fairview University of Minnesota Investigational Drug Services
Minneapolis, Minnesota, 55455
M Health Fairview University of Minnesota Medical Center-East Bank
Minneapolis, Minnesota, 55455
University of Minnesota/Lillehei Clinical Research Unit
Minneapolis, Minnesota, 55455
South Oklahoma Heart Research, LLC
Oklahoma City, Oklahoma, 73135
Reid Physician Associates
Richmond, Indiana, 47374
Washington University in St. Louis Center for Outpatient Health (COH)
St Louis, Missouri, 63108
Washington University in St. Louis Center for Advanced Medicine (CAM)
St Louis, Missouri, 63110
Washington University School of Medicine
St Louis, Missouri, 63110
Holy Name Medical Center
Teaneck, New Jersey, 07666
Traverse Heart & Vascular
Traverse City, Michigan, 49684
MedStar Washington Hospital Center
Washington D.C., District of Columbia, 20010
Canada17 sites
Saul Vizel Professional Medicine Corporation dba Vizel Cardiac Research
Cambridge, Ontario, N1R 7R1
QEII Health Sciences Centre - Victoria General Site
Halifax, Nova Scotia, B3H 3A7
University Hospital - London Health Sciences Centre
London, Ontario, N6A 5A5
Institut de Cardiologie de Montreal
Montreal, Quebec, H1T 1C8
Centre Hospitalier de l'Université de Montréal
Montreal, Quebec, H2X 3E4
Fraser Clinical Trials Inc
New Westminster, British Columbia, V3L 3W4
North York Diagnostic and Cardiac Centre
North York, Ontario, M6B 3H7
Private Practice - Dr. James Cha
Oshawa, Ontario, L1J 2K1
Kawartha Cardiology Clinical Trials
Peterborough, Ontario, K9J 0B2
Centre intégré de santé et de services sociaux du Bas Saint-Laurent- Hôpital régional de Rimouski
Rimouski, Quebec, G5L 5T1
CardioVasc HR Inc
Saint-Jean-sur-Richelieu, Quebec, J3A 1J2
Centre intégré de santé et de services sociaux de Lanaudière - Hopital Pierre-Le Gardeur.
Terrebonne, Quebec, J6V 2H2
Corcare
Toronto, Ontario, M1B 5N1
Unity Health Toronto, St. Michael's Hospital
Toronto, Ontario, M5B 1W8
Diex Recherche Trois-Rivieres
Trois-Rivières, Quebec, G9A 4P3
Community Care Building
Winchester, Ontario, K0C 2K0
Winchester District Memorial Hospital
Winchester, Ontario, K0C 2K0
Spain17 sites
CHUAC-Complejo Hospitalario Universitario A Coruña
A Coruña, A Coruña [LA Coruña], 15006
Parc de Salut Mar - Hospital del Mar
Barcelona, Barcelona [barcelona], 08003
Hospital Universitari Vall d'Hebron
Barcelona, Barcelona [barcelona], 08035
Hospital de la Santa Creu i Sant Pau
Barcelona, Catalunya [cataluña], 08041
Hospital Clínico Universitario Virgen de la Arrixaca
El Palmar, Murcia, Región de, 30120
Hospital Universitario Virgen Nieves
Granada, 18012
Hospital Universitari de Bellvitge
L'Hospitalet de Llobregat, Barcelona, 08907
Hospital Universitario Ramón y Cajal
Madrid, Madrid, Comunidad de, 28034
Hospital Universitario La Paz
Madrid, 28046
Hospital Universitario Puerta de Hierro Majadahonda
Majadahonda, Madrid, Comunidad de, 28222
Hospital Universitario Virgen de la Victoria
Málaga, 29010
Hospital Universitario Central de Asturias
Oviedo, 33011
CHUS - Hospital Clinico Universitario
Santiago de Compostela, A Coruña [LA Coruña], 15706
Hospital Universitario Virgen Del Rocio
Seville, 41013
Hospital Clinico de Valencia
Valencia, Valenciana, Comunitat, 46010
Hospital General Universitario de Valencia
Valencia, 46014
Hospital Universitari i Politecnic La Fe
Valencia, 46026
United Kingdom12 sites
Barnet Hospital
Barnet, EN5 3DJ
Royal Papworth Hospital NHS Foundation Trust
Cambridge, CB2 0AY
Golden Jubilee National Hospital
Clydebank, G81 4DY
Ninewells Hospital and Medical School
Dundee, Dundee CITY, DD1 9SY
Glasgow Royal Infirmary
Glasgow, Scotland, G31 2ER
Northwick Park Hospital
Harrow, London, CITY of, HA1 3UJ
Wycombe General Hospital
High Wycombe, Buckinghamshire, HP11 2TT
Lincoln County Hospital
Lincoln, LN2 5QY
Liverpool University Hospitals NHS Foundation Trust
Liverpool, L9 7AL
St. George's Hospital
London, England and Wales, SW17 0QT
Northern General Hospital
Sheffield, S5 7AU
University Hospital of North Tees
Stockton-on-Tees, TS19 8PE
China11 sites
Peking University First Hospital
Beijing, 100034
China-Japan Union Hospital
Changchun, Jilin, 130033
The Second Xiangya Hospital of Central South University
Changsha, Hunan, 410011
Guangdong Provincial People's Hospital
Guangzhou, Guangdong, 510080
The First Affiliated Hospital, Sun Yat-sen University
Guangzhou, Guangdong, 510080
The First Affiliated Hospital of University of South China
Hengyang, Hunan, 421001
Qilu Hospital of Shandong University
Jinan, Shandong, 250014
Zhongshan Hospital,Fudan University
Shanghai, Shanghai Municipality, 200032
Tianjin People' s Hospital
Tianjin, Tianjin Municipality, 300120
The First Affiliated Hospital of Xi'an Jiaotong University
Xi'an, Shaanxi, 710061
Yuncheng Central Hospital
Yuncheng, Shanxi, 044000
Japan10 sites
Hyogo Prefectural Amagasaki General Medical Center
Amagasaki, Hyōgo, 660-8550
Hyogo Prefectural Harima-Himeji General Medical Center
Himeji, Hyōgo, 670-8560
Kishiwada Tokushukai Hospital
Kishiwada, Osaka, 596-0042
Iwate Prefectural Central Hospital
Morioka, Iwate, 020-0066
Osaka General Medical Center
Osaka, 558-8558
National Hospital Organization Sendai Medical Center
Sendai, Miyagi, 983-8520
Keio University Hospital
Shinjuku-ku, Tokyo, 160-8582
National Cerebral and Cardiovascular Center
Suita, Osaka, 564-8565
Higashi Takarazuka Satoh Hospital
Takarazuka, Hyōgo, 665-0873
National Hospital Organization Saitama Hospital
Wako, Saitama, 351-0102
Hungary8 sites
Private Practice - Dr. Lakatos Ferenc
Békéscsaba, Bekes County, 5600
Dél-Pesti Centrumkórház Orszagos Hematologiai es Infektologiai Intezet
Budapest, 1097
Semmelweis Egyetem
Budapest, 1122
Somogy Vármegyei Kaposi Mór Oktató Kórház
Kaposvár, Somogy County, 7400
TaNa Med
Mosonmagyaróvár, Győr-Moson-Sopron, 9200
Kanizsai Dorottya Korhaz
Nagykanizsa, 8800
Medifarma 98 Kft
Nyíregyháza, Nyíregyháza, 4400
Pécsi Tudományegyetem Klinikai Központ
Pécs, Baranya, 7624
Poland8 sites
Uniwersytecki Szpital Kliniczny w Białymstoku
Bialystok, Podlaskie Voivodeship, 15-276
Kardio Brynow
Katowice, Silesian Voivodeship, 40-555
SPZOZ Centralny Szpital Kliniczny Uniwersytetu Medycznego w Lodzi
Lodz, 92-213
Miejski Szpital Zespolony w Olsztynie
Olsztyn, Warmian-Masurian Voivodeship, 10-045
Uniwersytecki Szpital Kliniczny w Poznaniu
Poznan, Greater Poland Voivodeship, 61-848
Polsko Amerykanskie Kliniki Serca
Tychy, 43-100
Uniwersyteckie Centrum Kliniczne Warszawskiego Uniwersytetu Medycznego Centralny Szpital Kliniczny
Warsaw, 02-097
Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wrocławiu
Wroclaw, Lower Silesian Voivodeship, 50-556
Czechia6 sites
Fakultni Nemocnice u sv. Anny v Brne
Brno, South Moravian, 602 00
EDUMED - Jaroměř
Jaroměř, Náchod, 551 01
Institut Klinicke a Experimentalni Mediciny
Prague, Praha 4, 140 21
Fakultni nemocnice Kralovske Vinohrady
Prague, 100 34
Vseobecna fakultni nemocnice v Praze
Prague, 12808
Ustredni vojenska nemocnice
Prague, 16902
Germany6 sites
Herz - und Diabeteszentrum Nordrhein - Westfalen, Bad Oeynhausen
Bad Oeynhausen, North Rhine-Westphalia, 32545
Hausärztlich-Kardiologisches MVZ am Felsenkeller GmbH/Zentrum für klinische Studien
Dresden, Saxony, 01277
Universitätsklinikum Frankfurt Goethe-Universität
Frankfurt am Main, Hesse, 60590
Universitätsmedizin Göttingen - Georg-August-Universität
Göttingen, Lower Saxony, 37075
Universitätsklinikum Jena
Jena, Thuringia, 07747
Universitätsklinikum Jena
Jena, Thuringia, 7743
Australia5 sites
Core Research Group
Brisbane, Queensland, 4064
The Prince Charles Hospital
Chermside, Queensland, 4032
Concord Repatriation General Hospital
Concord, New South Wales, 2139
Lyell McEwin Hospital
Elizabeth Vale, South Australia, 5112
The Alfred Hospital
Melbourne, Victoria, 3004
About this study
Official title: A PHASE 2, DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED, 4-ARM STUDY TO INVESTIGATE SYMPTOMS, FUNCTION, HEALTH-RELATED QUALITY OF LIFE AND SAFETY WITH REPEATED SUBCUTANEOUS ADMINISTRATION OF PONSEGROMAB VERSUS PLACEBO IN ADULT PARTICIPANTS 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 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.
Read the 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.
- Conditions
- Heart Failure
- Being tested
- Main cohort (Cohort A): Ponsegromab low dose, Main cohort (Cohort A): Ponsegromab medium dose, Main cohort (Cohort A): ponsegromab high dose, Main cohort (Cohort A): Matched placebo, Open-label, PK Cohort (Cohort B): ponsegromab low dose
- Keywords
- Heart Failure, N-terminal pro-B type natriuretic peptide, Kansas City Cardiomyopathy Questionnaire, Patient's Global Impression of Severity, Patient's Global Impression of Change, Patient Reported Outcome Measurement Information System, Growth differentiation factor 15, New York Heart Association
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Main cohort (Cohort A): Ponsegromab low doseDrug
Also called PF-06946860 low dose
Ponsegromab low dose subcutaneous injection
Main cohort (Cohort A): Ponsegromab medium doseDrug
Also called PF-06946860 medium dose
Ponsegromab medium dose subcutaneous injection
Main cohort (Cohort A): ponsegromab high doseDrug
Also called PF-06946860 high dose
Ponsegromab high dose subcutaneous injection
Main cohort (Cohort A): Matched placeboOther
Also called Placebo
Matched placebo subcutaneous injection
Open-label, PK Cohort (Cohort B): ponsegromab low doseDrug
Also called PF-06946860 low dose
ponsegromab low dose subcutaneous injection
Open-label, PK Cohort (Cohort B): ponsegromab medium doseDrug
Also called PF-06946860 medium dose
Ponsegromab medium dose subcutaneous injection
Open-label, PK Cohort (Cohort B): ponsegromab high doseDrug
Also called PF-06946860 high dose
Ponsegromab high dose subcutaneous injection
Optional Cohort C: Ponsegromab low doseDrug
Also called PF-06946860 low dose
Ponsegromab low dose subcutaneous injection
Optional Cohort C: Matched placeboOther
Also called Placebo
Matched placebo subcutaneous injection
Optional Cohort D: Ponsegromab high doseDrug
Also called PF-06946860 high dose
Ponsegromab high dose subcutaneous injection
Optional Cohort D: Matched placeboOther
Also called Placebo
Matched placebo subcutaneous injection
| Study group | Role | What they receive |
|---|---|---|
| Main cohort (Cohort A): ponsegromab low dose | Experimental | Participants will receive a low dose Q4W SC Receives: Drug: Main cohort (Cohort A): Ponsegromab low dose |
| Main cohort (Cohort A): ponsegromab medium dose | Experimental | Participants will receive a medium dose Q4W SC Receives: Drug: Main cohort (Cohort A): Ponsegromab medium dose |
| Main cohort (Cohort A): ponsegromab high dose | Experimental | Participants will receive a high dose Q4W SC Receives: Drug: Main cohort (Cohort A): ponsegromab high dose |
| Main cohort (Cohort A): placebo | Placebo comparator | matched placebo Receives: Other: Main cohort (Cohort A): Matched placebo |
| Open-label, PK Cohort (Cohort B): ponsegromab low dose | Experimental | Participants will receive a low dose Q4W SC Receives: Drug: Open-label, PK Cohort (Cohort B): ponsegromab low dose |
| Open-label, PK Cohort (Cohort B): ponsegromab medium dose | Experimental | Participants will receive a medium dose Q4W SC Receives: Drug: Open-label, PK Cohort (Cohort B): ponsegromab medium dose |
| Open-label, PK Cohort (Cohort B): ponsegromab high dose | Experimental | Participants will receive a high dose Q4W SC Receives: Drug: Open-label, PK Cohort (Cohort B): ponsegromab high dose |
| Optional Cohort C: ponsegromab low dose | Experimental | Participants will receive a low dose Q4W SC Receives: Drug: Optional Cohort C: Ponsegromab low dose |
| Optional Cohort C: placebo | Placebo comparator | matched placebo Receives: Other: Optional Cohort C: Matched placebo |
| Optional Cohort D: ponsegromab high dose | Experimental | Participants will receive a high dose Q4W SC Receives: Drug: Optional Cohort D: Ponsegromab high dose |
| Optional Cohort D: placebo | Placebo comparator | matched placebo Receives: Other: Optional Cohort D: Matched placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ)-23 - Clinical Summary Score (CSS) at Week 22: Cohort A, Ponsegromab 300 mg Versus Placebo
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.
Measured: Baseline [the last measurement on study Day 1], Week 22
Secondary outcomes (25)
Change From Baseline in KCCQ-23 CSS at Week 22: Cohort A
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.
Measured: Baseline [the last measurement on study Day 1], Week 22
Change From Baseline in KCCQ-23-Overall Summary Score (OSS) at Week 22: Cohort A, Ponsegromab 300 mg Versus Placebo
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.
Measured: Baseline [the last measurement on study Day 1], Week 22
Change From Baseline in KCCQ-23 OSS at Week 22: Cohort A
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.
Measured: Baseline [the last measurement on study Day 1], Week 22
Change From Baseline in KCCQ-23-TSS at Week 22: Cohort A, Ponsegromab 300 mg Versus Placebo
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.
Measured: Baseline [the last measurement on study Day 1], Week 22
Change From Baseline in KCCQ-23 TSS at Week 22: Cohort A
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.
Measured: Baseline [the last measurement on study Day 1], Week 22
Change From Baseline in KCCQ-23 Physical Limitation Score at Week 22: Cohort A, Ponsegromab 300 mg Versus Placebo
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.
Measured: Baseline [the last measurement on study Day 1], Week 22
Change From Baseline in KCCQ-23 Physical Limitation Score at Week 22: Cohort A
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.
Measured: Baseline [the last measurement on study Day 1], Week 22
Percentage of Participants With >= 5-Point Increase From Baseline in KCCQ-23-CSS at Week 22: Cohort A, Ponsegromab 300 mg Versus Placebo
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.
Measured: Week 22
Percentage of Participants With >= 5-Point Increase From Baseline in KCCQ-23 CSS Score at Week 22: Cohort A
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.
Measured: Week 22
Percentage of Participants With >= 5-Point Increase From Baseline in KCCQ-23 OSS Score at Week 22: Cohort A, Ponsegromab 300 mg Versus Placebo
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.
Measured: Week 22
Percentage of Participants With >= 5-Point Increase From Baseline in KCCQ-23 OSS Score at Week 22: Cohort A
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.
Measured: Week 22
Percentage of Participants With >= 5-Point Increase From Baseline in KCCQ-23 TSS Score at Week 22: Cohort A, Ponsegromab 300 mg Versus Placebo
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.
Measured: Week 22
Percentage of Participants With >= 5-Point Increase From Baseline in KCCQ-23 TSS Score at Week 22: Cohort A
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.
Measured: Week 22
Percentage of Participants With >= 5-Point Increase From Baseline in KCCQ-23 PL Score at Week 22: Cohort A, Ponsegromab 300 mg Versus Placebo
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.
Measured: Week 22
Percentage of Participants With >= 5-Point Increase From Baseline in KCCQ-23 PL Score at Week 22: Cohort A
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.
Measured: Week 22
Change From Baseline in 6-Minute Walk Distance (6MWD) at Week 22: Cohort A, Ponsegromab 300 mg Versus Placebo
The 6-minute walk test (6MWT) is a submaximal exercise test that entails measurement of distance walked over a span of 6 minutes. The 6MWD (distance travelled in meters) provides a measure for integrated global response of multiple cardiopulmonary and musculoskeletal systems involved in exercise.
Measured: Baseline [the last measurement on study Day 1], Week 22
Change From Baseline in 6MWD at Week 22: Cohort A
The 6MWT is a submaximal exercise test that entails measurement of distance walked over a span of 6 minutes. The 6MWD (distance travelled in meters) provides a measure for integrated global response of multiple cardiopulmonary and musculoskeletal systems involved in exercise.
Measured: Baseline [the last measurement on study Day 1], Week 22
Change From Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue (Version 7a) at Week 22: Cohort A, Ponsegromab 300 mg Versus Placebo
The PROMIS Fatigue 7a is a self-reported measure that assessed a range of symptoms in the past 7 days from mild subjective feelings of tiredness to an overwhelming, debilitating, and sustained sense of exhaustion that likely decreases one's ability to execute daily activities and function normally in family or social roles. The short form (SF) 7A consisted of 7 items that study participants rated from 1: "Never" to 5: "Always". A global raw score ranged from 7 to 35 was calculated and translated into a T-score with minimum of 29.4 and maximum of 83.2 (mean = 50, a standard deviation [SD] = 10) using the applicable score conversion provided in the PROMIS user's manual. Higher scores indicated more fatigue.
Measured: Baseline [the last measurement on study Day 1], Week 22
Change From Baseline in PROMIS Fatigue (Version 7a) at Week 22: Cohort A
The PROMIS Fatigue 7a is a self-reported measure that assessed a range of symptoms in the past 7 days from mild subjective feelings of tiredness to an overwhelming, debilitating, and sustained sense of exhaustion that likely decreases one's ability to execute daily activities and function normally in family or social roles. The short form (SF) 7A consisted of 7 items that study participants rated from 1: "Never" to 5: "Always". A global raw score ranged from 7 to 35 was calculated and translated into a T-score (mean = 50, a standard deviation [SD] = 10) using the applicable score conversion provided in the PROMIS user's manual. Higher scores indicated more fatigue.
Measured: Baseline [the last measurement on study Day 1], Week 22
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs): Cohort A
An adverse event (AE) was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE was considered a TEAE if the event started during the effective duration of treatment. TESAE was a TEAE which met the definition of serious adverse event (SAE) viz. any untoward medical occurrence at any dose that resulted in death; was life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect or was considered an important medical event. AEs included SAEs and all other AEs (non-SAEs).
Measured: From first dose of study treatment (Day 1) maximum up to 10 weeks post Week 22 (maximum up to approximately 32 weeks)
Number of Participants With Any Abnormalities in Laboratory Test Parameters: Cohort A
Laboratory parameters included were: hematology (hemoglobin, hematocrit, red blood cells [RBC] count, platelet count, white blood cells [WBC] count) and chemistry (urea and creatinine, estimated glomerular filtration rate [eGFR], cystatin C [at baseline only], sodium, potassium, aspartate aminotransferase [AST], alanine aminotransferase [ALT], total bilirubin, alkaline phosphatase [ALP], total protein, glucose [non-fasting] and lipid panel, total cholesterol, high-density lipoprotein [HDL] cholesterol, Non HDL cholesterol, calculated low-density lipoprotein [LDL] cholesterol and triglycerides. Number of participants with any abnormalities in laboratory test parameters as judged by investigator were reported.
Measured: From first dose of study treatment (Day 1) up to Week 22
Number of Participants With Abnormalities in Vital Signs: Cohort A
Vital signs abnormalities criteria included: supine systolic blood pressure (SBP) <90 millimeters of mercury (mmHg), increase and decrease in change of >= 30mmHg; supine diastolic blood pressure (DBP) <50 mmHg, increase and decrease in change of >=20mmHg; and pulse rate (PR) <40 beats per minute (bpm) and >120 bpm.
Measured: From first dose of study treatment (Day 1) maximum up to 10 weeks post Week 22 (maximum up to approximately 32 weeks)
Number of Participants With TEAEs and TEASAEs: Cohort B
An AE was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE was considered a TEAE if the event started during the effective duration of treatment. TESAE was a TEAE which met the definition of SAE viz. any untoward medical occurrence at any dose that resulted in death; was life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect or was considered an important medical event. AEs included SAEs and all other AEs (non-SAEs).
Measured: From first dose of study treatment (Day 1) maximum up to 10 weeks post Week 12 (maximum up to approximately 22 weeks)
Number of Participants With Any Abnormalities in Laboratory Test Parameters: Cohort B
Laboratory parameters included were: hematology (hemoglobin, hematocrit, RBC count, platelet count, WBC count) and chemistry (urea and creatinine, eGFR, cystatin C [at baseline only], sodium, potassium, AST, ALT, total bilirubin, ALP, total protein, glucose [non-fasting] and lipid panel, total cholesterol, HDL cholesterol, Non HDL cholesterol, calculated LDL cholesterol and triglycerides. Number of participants with any abnormalities in laboratory test parameters as judged by investigator were reported.
Measured: From first dose of study treatment (Day 1) maximum up to 4 weeks post Week 12 (maximum up to approximately 16 weeks)
Number of Participants With Abnormalities in Vital Signs: Cohort B
Vital signs criteria included: supine SBP <90 mmHg, increase and decrease in change of >= 30mmHg; supine DBP <50 mmHg, increase and decrease in change of >=20mmHg; and PR <40 bpm to >120 bpm.
Measured: From start of study drug on Day 1 maximum up to 4weeks post last dose on Week 12 (maximum up to approximately Week 16)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Aug 2022
- Study start26 Sep 2022
- Primary completion5 Mar 2025
- Study completion5 Mar 2025
Why it stopped: Following a prespecified interim analysis, and in consultation with the independent Data Monitoring Committee, the Sponsor terminated the study
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Heart FailureStudies of the same condition, open and under way.
- More trials run by PfizerThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- In the main cohort (Cohort A), ponsegromab will be administered at low, medium and high doses every 4 weeks by subcutaneous injections for a total of 6 doses. Participants will be randomized to 1 of the 3 doses of ponsegromab or placebo. In optional Cohort C, ponsegromab will be administered at low doses every 4 weeks by subcutaneous injections for a total of 6 doses. Participants will be randomized to the low dose of ponsegromab or placebo. In optional Cohort D, ponsegromab will be administered at high doses every 4 weeks by subcutaneous injections for a total of 6 doses. Participants will be randomized to the high dose of ponsegromab or placebo. In a separate open-label, PK cohort (Cohort B), ponsegromab will be administered at low, medium and high doses every 4 weeks by subcutaneous injections for a total of 4 doses. Participants will be randomized to 1 of the 3 doses of ponsegromab. There is no placebo in the open-label, PK cohort.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 455 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pfizer
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- The TIMI Study Group
- Responsible party
- Sponsor
- Investigators
- Pfizer CT.gov Call Center, Study director, Pfizer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05492500
- Sponsor's protocol ID
- C3651011
- Other IDs
- 2023-509747-27-00, 2023
- Acronym
- GARDEN TIMI 74
- Status last verified
- Feb 2026
- First submitted
- 25 Jul 2022
- Last updated
- 18 Mar 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\_trials/trial\_data\_and\_results/data\_requests.
Study at a glance
From the registry record, last updated by the sponsor on 18 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A PHASE 2, DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED, 4-ARM STUDY TO INVESTIGATE SYMPTOMS, FUNCTION, HEALTH-RELATED QUALITY OF LIFE AND SAFETY WITH REPEATED SUBCUTANEOUS ADMINISTRATION OF PONSEGROMAB VERSUS PLACEBO IN ADULT PARTICIPANTS WITH HEART FAILURE
- ClinicalTrials.gov ID
- NCT05492500
- Acronym / sponsor ID
- GARDEN TIMI 74 / C3651011
- Conditions
- Heart Failure
- Keywords
- Heart Failure, N-terminal pro-B type natriuretic peptide, Kansas City Cardiomyopathy Questionnaire, Patient's Global Impression of Severity, Patient's Global Impression of Change, Patient Reported Outcome Measurement Information System, Growth differentiation factor 15, New York Heart Association
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Following a prespecified interim analysis, and in consultation with the independent Data Monitoring Committee, the Sponsor terminated the study
- Enrolment
- 455 participants (actual)
- Lead sponsor
- PfizerIndustry (pharma, biotech, devices)
- Collaborators
- The TIMI Study Group
- Study start
- 26 Sep 2022 (actual)
- Primary completion
- 5 Mar 2025 (actual)
- Study completion
- 5 Mar 2025 (actual)
- First posted
- 8 Aug 2022 (actual)
- Results
- Posted 18 Mar 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 11
- Model description
- In the main cohort (Cohort A), ponsegromab will be administered at low, medium and high doses every 4 weeks by subcutaneous injections for a total of 6 doses. Participants will be randomized to 1 of the 3 doses of ponsegromab or placebo. In optional Cohort C, ponsegromab will be administered at low doses every 4 weeks by subcutaneous injections for a total of 6 doses. Participants will be randomized to the low dose of ponsegromab or placebo. In optional Cohort D, ponsegromab will be administered at high doses every 4 weeks by subcutaneous injections for a total of 6 doses. Participants will be randomized to the high dose of ponsegromab or placebo. In a separate open-label, PK cohort (Cohort B), ponsegromab will be administered at low, medium and high doses every 4 weeks by subcutaneous injections for a total of 4 doses. Participants will be randomized to 1 of the 3 doses of ponsegromab. There is no placebo in the open-label, PK cohort.
| Arm | Type | Receives |
|---|---|---|
| Main cohort (Cohort A): ponsegromab low dose | Experimental | Drug: Main cohort (Cohort A): Ponsegromab low doseParticipants will receive a low dose Q4W SC |
| Main cohort (Cohort A): ponsegromab medium dose | Experimental | Drug: Main cohort (Cohort A): Ponsegromab medium doseParticipants will receive a medium dose Q4W SC |
| Main cohort (Cohort A): ponsegromab high dose | Experimental | Drug: Main cohort (Cohort A): ponsegromab high doseParticipants will receive a high dose Q4W SC |
| Main cohort (Cohort A): placebo | Placebo comparator | Other: Main cohort (Cohort A): Matched placebomatched placebo |
| Open-label, PK Cohort (Cohort B): ponsegromab low dose | Experimental | Drug: Open-label, PK Cohort (Cohort B): ponsegromab low doseParticipants will receive a low dose Q4W SC |
| Open-label, PK Cohort (Cohort B): ponsegromab medium dose | Experimental | Drug: Open-label, PK Cohort (Cohort B): ponsegromab medium doseParticipants will receive a medium dose Q4W SC |
| Open-label, PK Cohort (Cohort B): ponsegromab high dose | Experimental | Drug: Open-label, PK Cohort (Cohort B): ponsegromab high doseParticipants will receive a high dose Q4W SC |
| Optional Cohort C: ponsegromab low dose | Experimental | Drug: Optional Cohort C: Ponsegromab low doseParticipants will receive a low dose Q4W SC |
| Optional Cohort C: placebo | Placebo comparator | Other: Optional Cohort C: Matched placebomatched placebo |
| Optional Cohort D: ponsegromab high dose | Experimental | Drug: Optional Cohort D: Ponsegromab high doseParticipants will receive a high dose Q4W SC |
| Optional Cohort D: placebo | Placebo comparator | Other: Optional Cohort D: Matched placebomatched placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Male and female participants aged 18 years or older
- 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]):
Key exclusion criteria (12 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Main cohort (Cohort A): Ponsegromab low doseAlso: PF-06946860 low dosePonsegromab low dose subcutaneous injection | Drug | Main cohort (Cohort A): ponsegromab low dose |
| Main cohort (Cohort A): Ponsegromab medium doseAlso: PF-06946860 medium dosePonsegromab medium dose subcutaneous injection | Drug | Main cohort (Cohort A): ponsegromab medium dose |
| Main cohort (Cohort A): ponsegromab high doseAlso: PF-06946860 high dosePonsegromab high dose subcutaneous injection | Drug | Main cohort (Cohort A): ponsegromab high dose |
| Main cohort (Cohort A): Matched placeboAlso: PlaceboMatched placebo subcutaneous injection | Other | Main cohort (Cohort A): placebo |
| Open-label, PK Cohort (Cohort B): ponsegromab low doseAlso: PF-06946860 low doseponsegromab low dose subcutaneous injection | Drug | Open-label, PK Cohort (Cohort B): ponsegromab low dose |
| Open-label, PK Cohort (Cohort B): ponsegromab medium doseAlso: PF-06946860 medium dosePonsegromab medium dose subcutaneous injection | Drug | Open-label, PK Cohort (Cohort B): ponsegromab medium dose |
| Open-label, PK Cohort (Cohort B): ponsegromab high doseAlso: PF-06946860 high dosePonsegromab high dose subcutaneous injection | Drug | Open-label, PK Cohort (Cohort B): ponsegromab high dose |
| Optional Cohort C: Ponsegromab low doseAlso: PF-06946860 low dosePonsegromab low dose subcutaneous injection | Drug | Optional Cohort C: ponsegromab low dose |
| Optional Cohort C: Matched placeboAlso: PlaceboMatched placebo subcutaneous injection | Other | Optional Cohort C: placebo |
| Optional Cohort D: Ponsegromab high doseAlso: PF-06946860 high dosePonsegromab high dose subcutaneous injection | Drug | Optional Cohort D: ponsegromab high dose |
| Optional Cohort D: Matched placeboAlso: PlaceboMatched placebo subcutaneous injection | Other | Optional Cohort D: placebo |
Primary outcome
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.
25 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
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
Change From Baseline in KCCQ-23 OSS at Week 22: Cohort A
Time frame: Baseline [the last measurement on study Day 1], Week 22
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
Change From Baseline in KCCQ-23 TSS at Week 22: Cohort A
Time frame: Baseline [the last measurement on study Day 1], Week 22
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
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
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
Percentage of Participants With >= 5-Point Increase From Baseline in KCCQ-23 CSS Score at Week 22: Cohort A
Time frame: Week 22
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
Percentage of Participants With >= 5-Point Increase From Baseline in KCCQ-23 OSS Score at Week 22: Cohort A
Time frame: Week 22
Percentage of Participants With >= 5-Point Increase From Baseline in KCCQ-23 TSS Score at Week 22: Cohort A, Ponsegromab 300 mg Versus Placebo
Time frame: Week 22
Percentage of Participants With >= 5-Point Increase From Baseline in KCCQ-23 TSS Score at Week 22: Cohort A
Time frame: Week 22
Percentage of Participants With >= 5-Point Increase From Baseline in KCCQ-23 PL Score at Week 22: Cohort A, Ponsegromab 300 mg Versus Placebo
Time frame: Week 22
Percentage of Participants With >= 5-Point Increase From Baseline in KCCQ-23 PL Score at Week 22: Cohort A
Time frame: Week 22
Change From Baseline in 6-Minute Walk Distance (6MWD) at Week 22: Cohort A, Ponsegromab 300 mg Versus Placebo
Time frame: Baseline [the last measurement on study Day 1], Week 22
Change From Baseline in 6MWD at Week 22: Cohort A
Time frame: Baseline [the last measurement on study Day 1], Week 22
Change From Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue (Version 7a) at Week 22: Cohort A, Ponsegromab 300 mg Versus Placebo
Time frame: Baseline [the last measurement on study Day 1], Week 22
Change From Baseline in PROMIS Fatigue (Version 7a) at Week 22: Cohort A
Time frame: Baseline [the last measurement on study Day 1], Week 22
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs): Cohort A
Time frame: From first dose of study treatment (Day 1) maximum up to 10 weeks post Week 22 (maximum up to approximately 32 weeks)
Number of Participants With Any Abnormalities in Laboratory Test Parameters: Cohort A
Time frame: From first dose of study treatment (Day 1) up to Week 22
Number of Participants With Abnormalities in Vital Signs: Cohort A
Time frame: From first dose of study treatment (Day 1) maximum up to 10 weeks post Week 22 (maximum up to approximately 32 weeks)
Number of Participants With TEAEs and TEASAEs: Cohort B
Time frame: From first dose of study treatment (Day 1) maximum up to 10 weeks post Week 12 (maximum up to approximately 22 weeks)
Number of Participants With Any Abnormalities in Laboratory Test Parameters: Cohort B
Time frame: From first dose of study treatment (Day 1) maximum up to 4 weeks post Week 12 (maximum up to approximately 16 weeks)
Number of Participants With Abnormalities in Vital Signs: Cohort B
Time frame: From start of study drug on Day 1 maximum up to 4weeks post last dose on Week 12 (maximum up to approximately Week 16)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Mar 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- To obtain contact information for a study center near you, click here.Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pfizer CT.gov Call Center study director
Pfizer
122 sites in 11 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Main cohort (Cohort A): Ponsegromab low dose, Main cohort (Cohort A): Ponsegromab medium dose and Main cohort (Cohort A): ponsegromab high dose in people with Heart Failure, run by Pfizer at 122 sites in 11 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 18 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 122 sites in United States, Canada, Spain, United Kingdom, China and 6 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Mar 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Mar 2026.