A Study of Ponsegromab in People With Heart Failure

Heart Failure Clinical Trial

— GARDEN TIMI 74  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05492500
• Other study ID #: C3651011
• Secondary ID: 2022-001809-5020
• Status: Recruiting
• Phase: Phase 2
• Start date: September 26, 2022
• Est. completion date: June 7, 2025

Study information

• Verified date: May 2024
• Source: Pfizer
• Contact: Pfizer CT.gov Call Center
• Phone: 1-800-718-1021
• Email: ClinicalTrials.gov_Inquiries[@]pfizer.com
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 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.

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 elevated 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 in the United States and Canada to facilitate a more comprehensive assessment of PK characteristics and PK/PD relationship for GDF-15 in participants with heart failure.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 416
• Est. completion date: June 7, 2025
• Est. primary completion date: March 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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. Main cohort only: NT-proBNP =400 pg/mL at screening.

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

• Main cohort only: KCCQ-23 CSS <75 at screening.

• Main cohort only: Evidence of cachexia or fatigue or functional impairment, as demonstrated by at least one of the following at screening:

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 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 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).

Related Conditions & MeSH terms

• Heart Failure

Intervention

Drug:
• Main cohort: Ponsegromab low dose
Ponsegromab low dose subcutaneous injection
• Main cohort: Ponsegromab medium dose
Ponsegromab medium dose subcutaneous injection
• Main cohort: ponsegromab high dose
Ponsegromab high dose subcutaneous injection

Other:
• Main cohort: Matched placebo
Matched placebo subcutaneous injection

Drug:
• Open-label, PK Cohort: ponsegromab low dose
ponsegromab low dose subcutaneous injection
• Open-label, PK Cohort: ponsegromab medium dose
Ponsegromab medium dose subcutaneous injection
• Open-label, PK Cohort: ponsegromab high dose
Ponsegromab high dose subcutaneous injection

Locations

Country	Name	City	State
Australia	Core Research Group	Brisbane	Queensland
Australia	The Prince Charles Hospital	Chermside	Queensland
Australia	Concord Repatriation General Hospital	Concord	New South Wales
Australia	Lyell McEwin Hospital	Elizabeth Vale	South Australia
Australia	The Alfred Hospital	Melbourne	Victoria
Australia	Gold Coast University Hospital	Southport	Queensland
Canada	Saul Vizel Professional Medicine Corporation dba Vizel Cardiac Research	Cambridge	Ontario
Canada	QEII Health Sciences Centre - Victoria General Site	Halifax	Nova Scotia
Canada	University Hospital - London Health Sciences Centre	London	Ontario
Canada	Institut de Cardiologie de Montreal	Montreal	Quebec
Canada	Centre Hospitalier de l'Université de Montréal	Montréal	Quebec
Canada	Fraser Clinical Trials Inc	New Westminster	British Columbia
Canada	North York Diagnostic and Cardiac Centre	North York	Ontario
Canada	Private Practice - Dr. James Cha	Oshawa	Ontario
Canada	Kawartha Cardiology Clinical Trials	Peterborough	Ontario
Canada	Centre intégré de santé et de services sociaux du Bas Saint-Laurent- Hôpital régional de Rimousk	Rimouski	Quebec
Canada	CardioVasc HR Inc	Saint-Jean-sur-Richelieu	Quebec
Canada	Centre intégré de santé et de services sociaux de Lanaudière - Hopital Pierre-Le Gardeur.	Terrebonne	Quebec
Canada	Corcare	Toronto	Ontario
Canada	Unity Health Toronto, St. Michael's Hospital	Toronto	Ontario
Canada	Diex Recherche Trois-Rivieres	Trois-Rivieres	Quebec
Canada	Winchester District Memorial Hospital	Winchester	Ontario
China	Peking University First Hospital	Beijing	Beijing
China	Peking University First Hospital	Beijing
China	China-Japan Union Hospital	Changchun	Jilin
China	The Second Xiangya Hospital of Central South University	Changsha	Hunan
China	The Second Xiangya Hospital of Central South University	Changsha	Hunan
China	Guangdong Provincial People's Hospital	Guangzhou	Guangdong
China	Guangdong Provincial People's Hospital	Guangzhou	Guangdong
China	The First Affiliated Hospital, Sun Yat-sen University	Guangzhou	Guangdong
China	The First Affiliated Hospital of University of South China	Hengyang	Hunan
China	Qilu Hospital of Shandong University	Jinan	Shandong
China	Zhongshan Hospital,Fudan University	Shanghai	Shanghai
China	Tianjin People' s Hospital	Tianjin	Tianjin
China	Tianjin People' s Hospital	Tianjin	Tianjin
China	The First Affiliated Hospital of Xi'an Jiaotong University	Xi'an	Shaanxi
China	Yuncheng Central Hospital	Yuncheng	Shanxi
Czechia	Fakultni Nemocnice u sv. Anny v Brne	Brno	Jihomoravský KRAJ
Czechia	EDUMED - Jaromer	Jaromer	Náchod
Czechia	Institut Klinicke a Experimentalni Mediciny	Prague	Praha 4
Czechia	Fakultni nemocnice Kralovske Vinohrady	Praha 10
Czechia	Vseobecna fakultni nemocnice v Praze	Praha 2
Czechia	Ustredni vojenska nemocnice	Praha 6
Germany	Herz - und Diabeteszentrum Nordrhein - Westfalen, Bad Oeynhausen	Bad Oeynhausen	Nordrhein-westfalen
Germany	Hausärztlich-Kardiologisches MVZ am Felsenkeller GmbH/Zentrum für klinische Studien	Dresden	Sachsen
Germany	Universitätsklinikum Frankfurt Goethe-Universität	Frankfurt	Hessen
Germany	Universitätsklinikum Frankfurt Goethe-Universität	Frankfurt	Hessen
Germany	Universitätsmedizin Göttingen - Georg-August-Universität	Göttingen	Niedersachsen
Germany	Universitätsklinikum Jena	Jena	Thuringia
Germany	Universitätsklinikum Jena	Jena	Thüringen
Hungary	Private Practice - Dr. Lakatos Ferenc	Békéscsaba	Békés
Hungary	Budai Irgalmasrendi Korhaz	Budapest
Hungary	Dél-Pesti Centrumkórház Orszagos Hematologiai es Infektologiai Intezet	Budapest
Hungary	Semmelweis Egyetem	Budapest
Hungary	Somogy Vármegyei Kaposi Mór Oktató Kórház	Kaposvár	Somogy
Hungary	Bacs-Kiskun Varmegyei Oktatokorhaz	Kecskemét	Bács-kiskun
Hungary	TaNa Med	Mosonmagyaróvár	Gyor-moson-sopron
Hungary	Kanizsai Dorottya Korhaz	Nagykanizsa
Hungary	Medifarma 98 Kft	Nyiregyhaza	Nyíregyháza
Hungary	Pécsi Tudományegyetem Klinikai Központ	Pécs	Baranya
Japan	Hyogo Prefectural Amagasaki General Medical Center	Amagasaki	Hyogo
Japan	Hyogo Prefectural Harima-Himeji General Medical Center	Himeji	Hyogo
Japan	Kishiwada Tokushukai Hospital	Kishiwada	Osaka
Japan	Saiseikai Kumamoto Hospital	Kumamoto
Japan	Iwate Prefectural Central Hospital	Morioka	Iwate
Japan	Osaka General Medical Center	Osaka
Japan	Sakurabashi Watanabe Hospital	Osaka-shi	Osaka
Japan	National Hospital Organization Sendai Medical Center	Sendai	Miyagi
Japan	Keio University Hospital	Shinjuku-ku	Tokyo
Japan	National Cerebral and Cardiovascular Center	Suita	Osaka
Japan	National Cerebral and Cardiovascular Center	Suita	Osaka
Japan	Osaka General Medical Center	Sumiyoshi Ward	Osaka
Japan	Higashi Takarazuka Satoh Hospital	Takarazuka	Hyogo
Japan	National Hospital Organization Saitama Hospital	Wako	Saitama
Poland	Uniwersytecki Szpital Kliniczny w Bialymstoku	Bialystok	Podlaskie
Poland	Gabinet Kardiologiczno Internistyczny	Gdynia	Pomorskie
Poland	Kardio Brynow	Katowice	Slaskie
Poland	SPZOZ Centralny Szpital Kliniczny Uniwersytetu Medycznego w Lodzi	Lodz
Poland	Miejski Szpital Zespolony w Olsztynie	Olsztyn	Warminsko-mazurskie
Poland	Uniwersytecki Szpital Kliniczny w Poznaniu	Poznan	Wielkopolskie
Poland	Polsko Amerykanskie Kliniki Serca	Tychy
Poland	Uniwersyteckie Centrum Kliniczne Warszawskiego Uniwersytetu Medycznego Centralny Szpital Kliniczny	Warsaw
Poland	Narodowy Instytut Kardiologii Stefana kardynala Wyszynskiego - Panstwowy Instytut Badawczy	Warszawa	Mazowieckie
Poland	Uniwersyteckie Centrum Kliniczne Warszawskiego Uniwersytetu Medycznego Centralny Szpital Kliniczny	Warszawa
Poland	Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wroclawiu	Wroclaw	Dolnoslaskie
Spain	CHUAC-Complejo Hospitalario Universitario A Coruña	A Coruña	A Coruña [LA Coruña]
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona	Catalunya [cataluña]
Spain	Hospital Universitari Vall d'Hebron	Barcelona	Barcelona [barcelona]
Spain	Parc de Salut Mar - Hospital del Mar	Barcelona	Barcelona [barcelona]
Spain	Hospital Clínico Universitario Virgen de la Arrixaca	El Palmar, Murcia	Murcia, Región DE
Spain	Hospital Universitario Virgen Nieves	Granada
Spain	Hospital Universitari de Bellvitge	L'Hospitalet de Llobregat	Barcelona
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitario Ramón y Cajal	Madrid	Madrid, Comunidad DE
Spain	Hospital Universitario Puerta de Hierro Majadahonda	Majadahonda	Madrid, Comunidad DE
Spain	Hospital Universitario Virgen de la Victoria	Málaga
Spain	Hospital Universitario Central de Asturias	Oviedo
Spain	CHUS - Hospital Clinico Universitario	Santiago de Compostela	A Coruña [LA Coruña]
Spain	Hospital Universitario Virgen Del Rocio	Sevilla
Spain	Hospital Clinico de Valencia	Valencia	Valenciana, Comunitat
Spain	Hospital General Universitario de Valencia	Valencia
Spain	Hospital Universitari i Politecnic La Fe	Valencia
United Kingdom	Barnet Hospital	Barnet
United Kingdom	Royal Papworth Hospital NHS Foundation Trust	Cambridge
United Kingdom	Golden Jubilee National Hospital	Clydebank
United Kingdom	Ninewells Hospital and Medical School	Dundee	Dundee CITY
United Kingdom	Glasgow Royal Infirmary	Glasgow	Scotland
United Kingdom	Northwick Park Hospital	Harrow	London, CITY OF
United Kingdom	Wycombe General Hospital	High Wycombe	Buckinghamshire
United Kingdom	Lincoln County Hospital	Lincoln
United Kingdom	Liverpool University Hospitals NHS Foundation Trust	Liverpool
United Kingdom	St. George's Hospital	London	England AND Wales
United Kingdom	Northern General Hospital	Sheffield
United Kingdom	University Hospital of North Tees	Stockton-On-Tees
United States	Emory University School of Medicine-Grady Campus	Atlanta	Georgia
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Clinical and Translational Research Center	Chapel Hill	North Carolina
United States	University of North Carolina Medical Center	Chapel Hill	North Carolina
United States	Texas Health Physicians Group	Dallas	Texas
United States	Henry Ford Hospital	Detroit	Michigan
United States	Eastern shore Research Institute LLC	Fairhope	Alabama
United States	Cardiology Associates of Fort Lauderdale	Fort Lauderdale	Florida
United States	Holy Cross Hospital	Fort Lauderdale	Florida
United States	Holy Cross Hospital/Jim Moran Heart & Vascular Research Institute	Fort Lauderdale	Florida
United States	Chicago Medical Research	Hazel Crest	Illinois
United States	Saint Luke's Hospital of Kansas City	Kansas City	Missouri
United States	Keck Medical Center of USC	Los Angeles	California
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	South Oklahoma Heart Research, LLC	Oklahoma City	Oklahoma
United States	Reid Physician Associates	Richmond	Indiana
United States	Washington University in St. Louis Center for Advanced Medicine (CAM)	Saint Louis	Missouri
United States	Washington University in St. Louis Center for Outpatient Health (COH)	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Holy Name Medical Center	Teaneck	New Jersey
United States	Traverse Heart & Vascular	Traverse City	Michigan
United States	MedStar Washington Hospital Center	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
Pfizer	Thrombolysis In Myocardial Infarction (TIMI)

Countries where clinical trial is conducted

United States,  Australia,  Canada,  China,  Czechia,  Germany,  Hungary,  Japan,  Poland,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Main cohort: Change from baseline in Kansas City Cardiomyopathy Questionnaire 23 Clinical Summary Score	To compare the effect of ponsegromab versus placebo, on heart failure disease-specific health status in participants with heart failure	baseline, 22 weeks
Secondary	Main cohort: Change from baseline in Kansas City Cardiomyopathy Questionnaire 23 Overall Summary Score	To compare the effect of ponsegromab versus placebo on HF disease-specific overall health status in participants with HF	baseline, 22 weeks
Secondary	Main cohort: Change from baseline in Kansas City Cardiomyopathy Questionnaire 23 Total Symptom Score	To compare the effect of ponsegromab versus placebo on HF disease-specific overall health status in participants with HF	baseline, 22 weeks
Secondary	Main cohort: Change from baseline in Kansas City Cardiomyopathy Questionnaire 23 physical limitations domain	To compare the effect of ponsegromab versus placebo on HF disease-specific overall health status in participants with HF	baseline, 22 weeks
Secondary	Main cohort: Responses as defined by a =5 point increase from baseline in Kansas City Cardiomyopathy Questionnaire 23 Clinical Summary Score	To compare the effect of ponsegromab versus placebo on HF disease-specific health status in participants with HF	baseline, 22 weeks
Secondary	Main cohort: Responses as defined by a =5 point increase from baseline in Overall Summary Score	To compare the effect of ponsegromab versus placebo on HF disease-specific health status in participants with HF	baseline, 22 weeks
Secondary	Main cohort: Responses as defined by a =5 point increase from baseline in Total Symptom Score	To compare the effect of ponsegromab versus placebo on HF disease-specific health status in participants with HF	baseline, 22 weeks
Secondary	Main cohort: Responses as defined by a =5 point increase from baseline in physical limitation	To compare the effect of ponsegromab versus placebo on HF disease-specific health status in participants with HF	baseline, 22 weeks
Secondary	Main cohort: Change from baseline in 6-Minute Walk Distance	To compare the effect of ponsegromab versus placebo on the physical function of participants with HF	baseline, 22 weeks
Secondary	Main cohort: Change from baseline in PROMIS-Fatigue 7a which will be completed by study participants on an electronic device, so as to compare the effect of ponsegromab versus placebo on fatigue as reported by participants with HF	To compare the effect of ponsegromab versus placebo on fatigue reported by participants with HF	baseline, 22 weeks
Secondary	Main cohort: Incidence of treatment-emergent adverse events	To describe the safety and tolerability of ponsegromab in participants with HF	32 weeks
Secondary	Main cohort: Incidence of treatment-emergent serious adverse events	To describe the safety and tolerability of ponsegromab in participants with HF	32 weeks
Secondary	Main cohort: Incidence of abnormal laboratory results	To describe the safety and tolerability of ponsegromab in participants with HF	32 weeks
Secondary	Main cohort: Incidence of abnormal vital signs	To describe the safety and tolerability of ponsegromab in participants with HF	32 weeks
Secondary	Open-Label, PK Cohort: Incidence of treatment-emergent adverse events	To describe the safety and tolerability of ponsegromab in participants with HF	22 weeks
Secondary	Open-Label, PK Cohort: Incidence of treatment-emergent serious adverse events	To describe the safety and tolerability of ponsegromab in participants with HF	22 weeks
Secondary	Open-Label, PK Cohort: Incidence of abnormal laboratory results	To describe the safety and tolerability of ponsegromab in participants with HF	22 weeks
Secondary	Open-Label, PK Cohort: Incidence of abnormal vital signs	To describe the safety and tolerability of ponsegromab in participants with HF	22 weeks

External Links

•   To obtain contact information for a study center near you, click here.