Study Stopped
Following a prespecified interim analysis, and in consultation with the independent Data Monitoring Committee, the Sponsor terminated the study
A Study of Ponsegromab in People With Heart Failure
GARDEN TIMI 74
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
2 other identifiers
interventional
455
11 countries
122
Brief Summary
The primary purpose of this clinical trial is to compare the effects of study medicine (Ponsegromab/PF-06946860) with a placebo (an injection that looks like the study medicine but does not contain the active medicine) to find out if the study medicine is better than the placebo (an injection that looks like the study medicine but does not contain the active medicine) for treatment of symptoms related to heart failure. Participants will not know which treatment group they are assigned to. Most participants in this study will receive the study medicine or placebo by shots under the skin every four weeks. People may be able to participate in this study if they have heart failure. Participants will take part in this study for about 9 months. During this time participants will visit the study clinic once a month. A separate PK cohort within this clinical trial will receive open-label study medicine (Ponsegromab/PF-06946860) only. Participants in this open-label, PK cohort will not receive placebo. These participants will receive the study medicine by shots under the skin every four weeks. People may be able to participate in this study cohort if they also have heart failure. Participants will take part in the open-label, PK cohort for about 7 months.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2 heart-failure
Started Sep 2022
Typical duration for phase_2 heart-failure
122 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 25, 2022
CompletedFirst Posted
Study publicly available on registry
August 8, 2022
CompletedStudy Start
First participant enrolled
September 26, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 5, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
March 5, 2025
CompletedResults Posted
Study results publicly available
March 18, 2026
CompletedMarch 18, 2026
February 1, 2026
2.4 years
July 25, 2022
February 25, 2026
February 25, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
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.
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
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
Baseline [the last measurement on study Day 1], Week 22
Change From Baseline in KCCQ-23 OSS at Week 22: Cohort A
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
Baseline [the last measurement on study Day 1], Week 22
Change From Baseline in KCCQ-23 TSS at Week 22: Cohort A
Baseline [the last measurement on study Day 1], Week 22
- +20 more secondary outcomes
Study Arms (11)
Main cohort (Cohort A): ponsegromab low dose
EXPERIMENTALParticipants will receive a low dose Q4W SC
Main cohort (Cohort A): ponsegromab medium dose
EXPERIMENTALParticipants will receive a medium dose Q4W SC
Main cohort (Cohort A): ponsegromab high dose
EXPERIMENTALParticipants will receive a high dose Q4W SC
Main cohort (Cohort A): placebo
PLACEBO COMPARATORmatched placebo
Open-label, PK Cohort (Cohort B): ponsegromab low dose
EXPERIMENTALParticipants will receive a low dose Q4W SC
Open-label, PK Cohort (Cohort B): ponsegromab medium dose
EXPERIMENTALParticipants will receive a medium dose Q4W SC
Open-label, PK Cohort (Cohort B): ponsegromab high dose
EXPERIMENTALParticipants will receive a high dose Q4W SC
Optional Cohort C: ponsegromab low dose
EXPERIMENTALParticipants will receive a low dose Q4W SC
Optional Cohort C: placebo
PLACEBO COMPARATORmatched placebo
Optional Cohort D: ponsegromab high dose
EXPERIMENTALParticipants will receive a high dose Q4W SC
Optional Cohort D: placebo
PLACEBO COMPARATORmatched placebo
Interventions
Ponsegromab low dose subcutaneous injection
Ponsegromab medium dose subcutaneous injection
Ponsegromab high dose subcutaneous injection
Matched placebo subcutaneous injection
ponsegromab low dose subcutaneous injection
Ponsegromab medium dose subcutaneous injection
Ponsegromab high dose subcutaneous injection
Ponsegromab low dose subcutaneous injection
Matched placebo subcutaneous injection
Ponsegromab high dose subcutaneous injection
Matched placebo subcutaneous injection
Eligibility Criteria
You may qualify if:
- 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.
- 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.
You may not qualify if:
- 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).
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Pfizerlead
- The TIMI Study Groupcollaborator
Study Sites (122)
Eastern shore Research Institute LLC
Fairhope, Alabama, 36532, United States
Keck Medical Center of USC
Los Angeles, California, 90033, United States
MedStar Washington Hospital Center
Washington D.C., District of Columbia, 20010, United States
Emory University School of Medicine-Grady Campus
Atlanta, Georgia, 30303, United States
Chicago Medical Research
Hazel Crest, Illinois, 60429, United States
Reid Physician Associates
Richmond, Indiana, 47374, United States
Brigham and Women's Hospital
Boston, Massachusetts, 02115, United States
Henry Ford Hospital
Detroit, Michigan, 48202, United States
Traverse Heart & Vascular
Traverse City, Michigan, 49684, United States
M Health Fairview Clinics and Surgery Center
Minneapolis, Minnesota, 55455, United States
M Health Fairview University of Minnesota Investigational Drug Services
Minneapolis, Minnesota, 55455, United States
M Health Fairview University of Minnesota Medical Center-East Bank
Minneapolis, Minnesota, 55455, United States
University of Minnesota/Lillehei Clinical Research Unit
Minneapolis, Minnesota, 55455, United States
Saint Luke's Hospital of Kansas City
Kansas City, Missouri, 64111, United States
Washington University in St. Louis Center for Outpatient Health (COH)
St Louis, Missouri, 63108, United States
Washington University in St. Louis Center for Advanced Medicine (CAM)
St Louis, Missouri, 63110, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Holy Name Medical Center
Teaneck, New Jersey, 07666, United States
University of North Carolina Medical Center
Chapel Hill, North Carolina, 27514, United States
Clinical and Translational Research Center
Chapel Hill, North Carolina, 27599, United States
South Oklahoma Heart Research, LLC
Oklahoma City, Oklahoma, 73135, United States
Texas Health Heart & Vascular Specialist (THHVS) #18760
Dallas, Texas, 75231, United States
Concord Repatriation General Hospital
Concord, New South Wales, 2139, Australia
Core Research Group
Brisbane, Queensland, 4064, Australia
The Prince Charles Hospital
Chermside, Queensland, 4032, Australia
Lyell McEwin Hospital
Elizabeth Vale, South Australia, 5112, Australia
The Alfred Hospital
Melbourne, Victoria, 3004, Australia
Fraser Clinical Trials Inc
New Westminster, British Columbia, V3L 3W4, Canada
QEII Health Sciences Centre - Victoria General Site
Halifax, Nova Scotia, B3H 3A7, Canada
Saul Vizel Professional Medicine Corporation dba Vizel Cardiac Research
Cambridge, Ontario, N1R 7R1, Canada
University Hospital - London Health Sciences Centre
London, Ontario, N6A 5A5, Canada
North York Diagnostic and Cardiac Centre
North York, Ontario, M6B 3H7, Canada
Private Practice - Dr. James Cha
Oshawa, Ontario, L1J 2K1, Canada
Kawartha Cardiology Clinical Trials
Peterborough, Ontario, K9J 0B2, Canada
Corcare
Toronto, Ontario, M1B 5N1, Canada
Unity Health Toronto, St. Michael's Hospital
Toronto, Ontario, M5B 1W8, Canada
Community Care Building
Winchester, Ontario, K0C 2K0, Canada
Winchester District Memorial Hospital
Winchester, Ontario, K0C 2K0, Canada
Institut de Cardiologie de Montreal
Montreal, Quebec, H1T 1C8, Canada
Centre Hospitalier de l'Université de Montréal
Montreal, Quebec, H2X 3E4, Canada
Centre intégré de santé et de services sociaux du Bas Saint-Laurent- Hôpital régional de Rimouski
Rimouski, Quebec, G5L 5T1, Canada
CardioVasc HR Inc
Saint-Jean-sur-Richelieu, Quebec, J3A 1J2, Canada
Centre intégré de santé et de services sociaux de Lanaudière - Hopital Pierre-Le Gardeur.
Terrebonne, Quebec, J6V 2H2, Canada
Diex Recherche Trois-Rivieres
Trois-Rivières, Quebec, G9A 4P3, Canada
Guangdong Provincial People's Hospital
Guangzhou, Guangdong, 510080, China
The First Affiliated Hospital, Sun Yat-sen University
Guangzhou, Guangdong, 510080, China
The Second Xiangya Hospital of Central South University
Changsha, Hunan, 410011, China
The First Affiliated Hospital of University of South China
Hengyang, Hunan, 421001, China
China-Japan Union Hospital
Changchun, Jilin, 130033, China
The First Affiliated Hospital of Xi'an Jiaotong University
Xi'an, Shaanxi, 710061, China
Qilu Hospital of Shandong University
Jinan, Shandong, 250014, China
Zhongshan Hospital,Fudan University
Shanghai, Shanghai Municipality, 200032, China
Yuncheng Central Hospital
Yuncheng, Shanxi, 044000, China
Tianjin People' s Hospital
Tianjin, Tianjin Municipality, 300120, China
Peking University First Hospital
Beijing, 100034, China
EDUMED - Jaroměř
Jaroměř, Náchod, 551 01, Czechia
Institut Klinicke a Experimentalni Mediciny
Prague, Praha 4, 140 21, Czechia
Fakultni Nemocnice u sv. Anny v Brne
Brno, South Moravian, 602 00, Czechia
Fakultni nemocnice Kralovske Vinohrady
Prague, 100 34, Czechia
Vseobecna fakultni nemocnice v Praze
Prague, 12808, Czechia
Ustredni vojenska nemocnice
Prague, 16902, Czechia
Universitätsklinikum Frankfurt Goethe-Universität
Frankfurt am Main, Hesse, 60590, Germany
Universitätsmedizin Göttingen - Georg-August-Universität
Göttingen, Lower Saxony, 37075, Germany
Herz - und Diabeteszentrum Nordrhein - Westfalen, Bad Oeynhausen
Bad Oeynhausen, North Rhine-Westphalia, 32545, Germany
Hausärztlich-Kardiologisches MVZ am Felsenkeller GmbH/Zentrum für klinische Studien
Dresden, Saxony, 01277, Germany
Universitätsklinikum Jena
Jena, Thuringia, 07747, Germany
Universitätsklinikum Jena
Jena, Thuringia, 7743, Germany
Pécsi Tudományegyetem Klinikai Központ
Pécs, Baranya, 7624, Hungary
Private Practice - Dr. Lakatos Ferenc
Békéscsaba, Bekes County, 5600, Hungary
TaNa Med
Mosonmagyaróvár, Győr-Moson-Sopron, 9200, Hungary
Medifarma 98 Kft
Nyíregyháza, Nyíregyháza, 4400, Hungary
Somogy Vármegyei Kaposi Mór Oktató Kórház
Kaposvár, Somogy County, 7400, Hungary
Dél-Pesti Centrumkórház Orszagos Hematologiai es Infektologiai Intezet
Budapest, 1097, Hungary
Semmelweis Egyetem
Budapest, 1122, Hungary
Kanizsai Dorottya Korhaz
Nagykanizsa, 8800, Hungary
Hyogo Prefectural Amagasaki General Medical Center
Amagasaki, Hyōgo, 660-8550, Japan
Hyogo Prefectural Harima-Himeji General Medical Center
Himeji, Hyōgo, 670-8560, Japan
Higashi Takarazuka Satoh Hospital
Takarazuka, Hyōgo, 665-0873, Japan
Iwate Prefectural Central Hospital
Morioka, Iwate, 020-0066, Japan
National Hospital Organization Sendai Medical Center
Sendai, Miyagi, 983-8520, Japan
Kishiwada Tokushukai Hospital
Kishiwada, Osaka, 596-0042, Japan
National Cerebral and Cardiovascular Center
Suita, Osaka, 564-8565, Japan
National Hospital Organization Saitama Hospital
Wako, Saitama, 351-0102, Japan
Keio University Hospital
Shinjuku-ku, Tokyo, 160-8582, Japan
Osaka General Medical Center
Osaka, 558-8558, Japan
Uniwersytecki Szpital Kliniczny w Poznaniu
Poznan, Greater Poland Voivodeship, 61-848, Poland
Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wrocławiu
Wroclaw, Lower Silesian Voivodeship, 50-556, Poland
Uniwersytecki Szpital Kliniczny w Białymstoku
Bialystok, Podlaskie Voivodeship, 15-276, Poland
Kardio Brynow
Katowice, Silesian Voivodeship, 40-555, Poland
Miejski Szpital Zespolony w Olsztynie
Olsztyn, Warmian-Masurian Voivodeship, 10-045, Poland
SPZOZ Centralny Szpital Kliniczny Uniwersytetu Medycznego w Lodzi
Lodz, 92-213, Poland
Polsko Amerykanskie Kliniki Serca
Tychy, 43-100, Poland
Uniwersyteckie Centrum Kliniczne Warszawskiego Uniwersytetu Medycznego Centralny Szpital Kliniczny
Warsaw, 02-097, Poland
CHUAC-Complejo Hospitalario Universitario A Coruña
A Coruña, A Coruña [LA Coruña], 15006, Spain
CHUS - Hospital Clinico Universitario
Santiago de Compostela, A Coruña [LA Coruña], 15706, Spain
Parc de Salut Mar - Hospital del Mar
Barcelona, Barcelona [barcelona], 08003, Spain
Hospital Universitari Vall d'Hebron
Barcelona, Barcelona [barcelona], 08035, Spain
Hospital Universitari de Bellvitge
L'Hospitalet de Llobregat, Barcelona, 08907, Spain
Hospital de la Santa Creu i Sant Pau
Barcelona, Catalunya [cataluña], 08041, Spain
Hospital Universitario Ramón y Cajal
Madrid, Madrid, Comunidad de, 28034, Spain
Hospital Universitario Puerta de Hierro Majadahonda
Majadahonda, Madrid, Comunidad de, 28222, Spain
Hospital Clínico Universitario Virgen de la Arrixaca
El Palmar, Murcia, Región de, 30120, Spain
Hospital Clinico de Valencia
Valencia, Valenciana, Comunitat, 46010, Spain
Hospital Universitario Virgen Nieves
Granada, 18012, Spain
Hospital Universitario La Paz
Madrid, 28046, Spain
Hospital Universitario Virgen de la Victoria
Málaga, 29010, Spain
Hospital Universitario Central de Asturias
Oviedo, 33011, Spain
Hospital Universitario Virgen Del Rocio
Seville, 41013, Spain
Hospital General Universitario de Valencia
Valencia, 46014, Spain
Hospital Universitari i Politecnic La Fe
Valencia, 46026, Spain
Wycombe General Hospital
High Wycombe, Buckinghamshire, HP11 2TT, United Kingdom
Ninewells Hospital and Medical School
Dundee, Dundee CITY, DD1 9SY, United Kingdom
St. George's Hospital
London, England and Wales, SW17 0QT, United Kingdom
Northwick Park Hospital
Harrow, London, CITY of, HA1 3UJ, United Kingdom
Glasgow Royal Infirmary
Glasgow, Scotland, G31 2ER, United Kingdom
Barnet Hospital
Barnet, EN5 3DJ, United Kingdom
Royal Papworth Hospital NHS Foundation Trust
Cambridge, CB2 0AY, United Kingdom
Golden Jubilee National Hospital
Clydebank, G81 4DY, United Kingdom
Lincoln County Hospital
Lincoln, LN2 5QY, United Kingdom
Liverpool University Hospitals NHS Foundation Trust
Liverpool, L9 7AL, United Kingdom
Northern General Hospital
Sheffield, S5 7AU, United Kingdom
University Hospital of North Tees
Stockton-on-Tees, TS19 8PE, United Kingdom
Related Links
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Pfizer ClinicalTrials.gov Call Center
- Organization
- Pfizer Inc.
Study Officials
- STUDY DIRECTOR
Pfizer CT.gov Call Center
Pfizer
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Masking Details
- In the main cohort (Cohort A), Cohort C and Cohort D, investigators, sponsor, participants and other site staff will be blinded to participants' assigned study intervention, including the site staff assigned to prepare and administer the study intervention. Pharmacists and site personnel will be blinded to study intervention versus placebo within each study arm. The separate PK cohort (Cohort B) will be open-label and study treatment will be prepared and administered as per treatment assignment by qualified personnel. There is no blinding in the open-label, PK cohort (Cohort B).
- Purpose
- SUPPORTIVE CARE
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 25, 2022
First Posted
August 8, 2022
Study Start
September 26, 2022
Primary Completion
March 5, 2025
Study Completion
March 5, 2025
Last Updated
March 18, 2026
Results First Posted
March 18, 2026
Record last verified: 2026-02
Data Sharing
- IPD Sharing
- Will share
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.