A Study of Ponsegromab in People With Heart Failure
- Conditions
- Heart Failure
- Registration Number
- NCT05492500
- Lead Sponsor
- Pfizer
- 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.
- 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 456
-
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.
- Acute decompensated HF within 1 month prior to Screening Visit 1 or during the screening period.
- Implantation of a cardiac resynchronization therapy device or valve repair or replacement within 3 months prior to randomization or intent to do so during the trial.
For the open-label, PK cohort (Cohort B) only: implantation of a cardiac resynchronization therapy device more than 1 month prior to randomization is permitted.
- History of heart transplantation, currently listed for heart transplant, current/planned mechanical circulatory support, or current/planned use of intravenous inotropes (eg, dobutamine, milrinone).
- Acute coronary syndrome within 1 month prior to randomization.
- Coronary revascularization (percutaneous coronary intervention or coronary artery bypass grafting) within 3 months prior to randomization or intent to undergo coronary revascularization during the trial.
For the open-label, PK cohort (Cohort B) only: coronary revascularization more than 1 month prior to randomization is permitted.
- Untreated indication for an implantable cardiac defibrillator or pacemaker to treat a cardiac rhythm abnormality (ie, tachyarrhythmia or bradyarrhythmia).
- Previous administration with an investigational product (drug or vaccine) within 30 days (or as determined by the local requirement) or 5 half lives (whichever is longer) preceding the first dose of study intervention used in this study. Treatment with an investigational biologic agent within 6 months or 5 half-lives (whichever is longer) of Day 1.
- Previous exposure to ponsegromab in a prior clinical study.
- Renal disease requiring ongoing dialysis.
- Cirrhosis with evidence of portal hypertension not due to HF, or the following LFT abnormalities at the time of screening, confirmed by a repeat test if deemed necessary: AST or ALT level ≥ 3 x ULN, or total bilirubin level ≥ 2 x ULN (unless history of Gilbert's syndrome).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Primary Outcome Measures
Name Time Method Main cohort (Cohort A): Change from baseline in Kansas City Cardiomyopathy Questionnaire 23 Clinical Summary Score baseline, 22 weeks To compare the effect of high dose ponsegromab versus placebo, on heart failure disease-specific health status in participants with HF and elevated serum GDF-15 concentrations
- Secondary Outcome Measures
Name Time Method Main cohort (Cohort A): Responses as defined by a ≥5 point increase from baseline in Kansas City Cardiomyopathy Questionnaire 23 Clinical Summary Score baseline, 22 weeks To compare the effect of ponsegromab versus placebo on HF disease-specific health status in participants with HF and elevated serum GDF-15 concentrations
Main cohort (Cohort A): Change from baseline in Kansas City Cardiomyopathy Questionnaire 23 Overall Summary Score baseline, 22 weeks To compare the effect of ponsegromab versus placebo on HF disease-specific overall health status in participants with HF and elevated serum GDF-15 concentrations
Main cohort (Cohort A): Change from baseline in Kansas City Cardiomyopathy Questionnaire 23 Total Symptom Score baseline, 22 weeks To compare the effect of ponsegromab versus placebo on HF disease-specific overall health status in participants with HF and elevated serum GDF-15 concentrations
Main cohort (Cohort A): Change from baseline in Kansas City Cardiomyopathy Questionnaire 23 physical limitations domain baseline, 22 weeks To compare the effect of ponsegromab versus placebo on HF disease-specific overall health status in participants with HF and elevated serum GDF-15 concentrations
Main cohort (Cohort A): Responses as defined by a ≥5 point increase from baseline in Overall Summary Score baseline, 22 weeks To compare the effect of ponsegromab versus placebo on HF disease-specific health status in participants with HF and elevated serum GDF-15 concentrations
Main cohort (Cohort A): Responses as defined by a ≥5 point increase from baseline in Total Symptom Score baseline, 22 weeks To compare the effect of ponsegromab versus placebo on HF disease-specific health status in participants with HF and elevated serum GDF-15 concentrations
Main cohort (Cohort A): Responses as defined by a ≥5 point increase from baseline in physical limitation baseline, 22 weeks To compare the effect of ponsegromab versus placebo on HF disease-specific health status in participants with HF and elevated serum GDF-15 concentrations
Main cohort (Cohort A): Change from baseline in 6-Minute Walk Distance baseline, 22 weeks To compare the effect of ponsegromab versus placebo on the physical function of participants with HF and elevated serum GDF-15 concentrations
Main cohort (Cohort A): Change from baseline in PROMIS-Fatigue 7a which will be completed by study participants on an electronic device, so as to compare the effect of ponsegromab versus placebo on fatigue as reported by participants with HF baseline, 22 weeks To compare the effect of ponsegromab versus placebo on fatigue reported by participants with HF and elevated serum GDF-15 concentrations
Main cohort (Cohort A)/Cohort C/Cohort D: Incidence of treatment-emergent adverse events 32 weeks To describe the safety and tolerability of ponsegromab in participants with HF
Main cohort (Cohort A)/Cohort C/Cohort D: Incidence of treatment-emergent serious adverse events 32 weeks To describe the safety and tolerability of ponsegromab in participants with HF
Main cohort (Cohort A)/Cohort C/Cohort D: Incidence of abnormal laboratory results 32 weeks To describe the safety and tolerability of ponsegromab in participants with HF
Main cohort (Cohort A)/Cohort C/Cohort D: Incidence of abnormal vital signs 32 weeks To describe the safety and tolerability of ponsegromab in participants with HF
Open-Label, PK Cohort (Cohort B): Incidence of treatment-emergent adverse events 22 weeks To describe the safety and tolerability of ponsegromab in participants with HF
Open-Label, PK Cohort (Cohort B): Incidence of treatment-emergent serious adverse events 22 weeks To describe the safety and tolerability of ponsegromab in participants with HF
Open-Label, PK Cohort (Cohort B): Incidence of abnormal laboratory results 22 weeks To describe the safety and tolerability of ponsegromab in participants with HF
Open-Label, PK Cohort (Cohort B): Incidence of abnormal vital signs 22 weeks To describe the safety and tolerability of ponsegromab in participants with HF
Trial Locations
- Locations (121)
Vseobecna fakultni nemocnice v Praze
🇨🇿Praha 2, Czechia
Ustredni vojenska nemocnice
🇨🇿Praha 6, Czechia
Universitätsklinikum Frankfurt Goethe-Universität
🇩🇪Frankfurt, Hessen, Germany
SPZOZ Centralny Szpital Kliniczny Uniwersytetu Medycznego w Lodzi
🇵🇱Lodz, Poland
Polsko Amerykanskie Kliniki Serca
🇵🇱Tychy, Poland
Hospital Universitario Virgen de la Victoria
🇪🇸Málaga, Spain
Lincoln County Hospital
🇬🇧Lincoln, United Kingdom
CardioVasc HR Inc
🇨🇦Saint-Jean-sur-Richelieu, Quebec, Canada
Kawartha Cardiology Clinical Trials
🇨🇦Peterborough, Ontario, Canada
Corcare
🇨🇦Toronto, Ontario, Canada
Unity Health Toronto, St. Michael's Hospital
🇨🇦Toronto, Ontario, Canada
Community Care Building
🇨🇦Winchester, Ontario, Canada
Winchester District Memorial Hospital
🇨🇦Winchester, Ontario, Canada
Pécsi Tudományegyetem Klinikai Központ
🇭🇺Pécs, Baranya, Hungary
Private Practice - Dr. Lakatos Ferenc
🇭🇺Békéscsaba, Békés, Hungary
Eastern shore Research Institute LLC
🇺🇸Fairhope, Alabama, United States
Keck Medical Center of USC
🇺🇸Los Angeles, California, United States
MedStar Washington Hospital Center
🇺🇸Washington, District of Columbia, United States
Emory University School of Medicine-Grady Campus
🇺🇸Atlanta, Georgia, United States
Chicago Medical Research
🇺🇸Hazel Crest, Illinois, United States
Reid Physician Associates
🇺🇸Richmond, Indiana, United States
Brigham and Women's Hospital
🇺🇸Boston, Massachusetts, United States
Henry Ford Hospital
🇺🇸Detroit, Michigan, United States
Traverse Heart & Vascular
🇺🇸Traverse City, Michigan, United States
M Health Fairview Clinics and Surgery Center
🇺🇸Minneapolis, Minnesota, United States
M Health Fairview University of Minnesota Investigational Drug Services
🇺🇸Minneapolis, Minnesota, United States
M Health Fairview University of Minnesota Medical Center-East Bank
🇺🇸Minneapolis, Minnesota, United States
University of Minnesota/Lillehei Clinical Research Unit
🇺🇸Minneapolis, Minnesota, United States
Saint Luke's Hospital of Kansas City
🇺🇸Kansas City, Missouri, United States
Washington University in St. Louis Center for Outpatient Health (COH)
🇺🇸Saint Louis, Missouri, United States
Washington University in St. Louis Center for Advanced Medicine (CAM)
🇺🇸Saint Louis, Missouri, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Holy Name Medical Center
🇺🇸Teaneck, New Jersey, United States
University of North Carolina Medical Center
🇺🇸Chapel Hill, North Carolina, United States
Clinical and Translational Research Center
🇺🇸Chapel Hill, North Carolina, United States
South Oklahoma Heart Research, LLC
🇺🇸Oklahoma City, Oklahoma, United States
Texas Health Physicians Group
🇺🇸Dallas, Texas, United States
Concord Repatriation General Hospital
🇦🇺Concord, New South Wales, Australia
Core Research Group
🇦🇺Brisbane, Queensland, Australia
The Prince Charles Hospital
🇦🇺Chermside, Queensland, Australia
Lyell McEwin Hospital
🇦🇺Elizabeth Vale, South Australia, Australia
The Alfred Hospital
🇦🇺Melbourne, Victoria, Australia
Fraser Clinical Trials Inc
🇨🇦New Westminster, British Columbia, Canada
QEII Health Sciences Centre - Victoria General Site
🇨🇦Halifax, Nova Scotia, Canada
Saul Vizel Professional Medicine Corporation dba Vizel Cardiac Research
🇨🇦Cambridge, Ontario, Canada
University Hospital - London Health Sciences Centre
🇨🇦London, Ontario, Canada
North York Diagnostic and Cardiac Centre
🇨🇦North York, Ontario, Canada
Private Practice - Dr. James Cha
🇨🇦Oshawa, Ontario, Canada
Institut de Cardiologie de Montreal
🇨🇦Montreal, Quebec, Canada
Centre Hospitalier de l'Université de Montréal
🇨🇦Montréal, Quebec, Canada
Centre intégré de santé et de services sociaux du Bas Saint-Laurent- Hôpital régional de Rimouski
🇨🇦Rimouski, Quebec, Canada
Centre intégré de santé et de services sociaux de Lanaudière - Hopital Pierre-Le Gardeur.
🇨🇦Terrebonne, Quebec, Canada
Diex Recherche Trois-Rivieres
🇨🇦Trois-Rivieres, Quebec, Canada
Guangdong Provincial People's Hospital
🇨🇳Guangzhou, Guangdong, China
The First Affiliated Hospital, Sun Yat-sen University
🇨🇳Guangzhou, Guangdong, China
The Second Xiangya Hospital of Central South University
🇨🇳Changsha, Hunan, China
The First Affiliated Hospital of University of South China
🇨🇳Hengyang, Hunan, China
China-Japan Union Hospital
🇨🇳Changchun, Jilin, China
The First Affiliated Hospital of Xi'an Jiaotong University
🇨🇳Xi'an, Shaanxi, China
Qilu Hospital of Shandong University
🇨🇳Jinan, Shandong, China
Zhongshan Hospital,Fudan University
🇨🇳Shanghai, Shanghai, China
Yuncheng Central Hospital
🇨🇳Yuncheng, Shanxi, China
Tianjin People' s Hospital
🇨🇳Tianjin, Tianjin, China
Peking University First Hospital
🇨🇳Beijing, China
Fakultni Nemocnice u sv. Anny v Brne
🇨🇿Brno, Jihomoravský KRAJ, Czechia
EDUMED - Jaroměř
🇨🇿Jaroměř, Náchod, Czechia
Institut Klinicke a Experimentalni Mediciny
🇨🇿Prague, Praha 4, Czechia
Fakultni nemocnice Kralovske Vinohrady
🇨🇿Praha 10, Czechia
Universitätsmedizin Göttingen - Georg-August-Universität
🇩🇪Göttingen, Niedersachsen, 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 Jena
🇩🇪Jena, Thüringen, Germany
TaNa Med
🇭🇺Mosonmagyaróvár, Győr-moson-sopron, Hungary
Medifarma 98 Kft
🇭🇺Nyiregyhaza, Nyíregyháza, Hungary
Somogy Vármegyei Kaposi Mór Oktató Kórház
🇭🇺Kaposvár, Somogy, Hungary
Dél-Pesti Centrumkórház Orszagos Hematologiai es Infektologiai Intezet
🇭🇺Budapest, Hungary
Semmelweis Egyetem
🇭🇺Budapest, Hungary
Kanizsai Dorottya Korhaz
🇭🇺Nagykanizsa, Hungary
Hyogo Prefectural Amagasaki General Medical Center
🇯🇵Amagasaki, Hyogo, Japan
Hyogo Prefectural Harima-Himeji General Medical Center
🇯🇵Himeji, Hyogo, Japan
Higashi Takarazuka Satoh Hospital
🇯🇵Takarazuka, Hyogo, Japan
Iwate Prefectural Central Hospital
🇯🇵Morioka, Iwate, Japan
National Hospital Organization Sendai Medical Center
🇯🇵Sendai, Miyagi, Japan
Kishiwada Tokushukai Hospital
🇯🇵Kishiwada, Osaka, Japan
National Cerebral and Cardiovascular Center
🇯🇵Suita, Osaka, Japan
National Hospital Organization Saitama Hospital
🇯🇵Wako, Saitama, Japan
Keio University Hospital
🇯🇵Shinjuku-ku, Tokyo, Japan
Osaka General Medical Center
🇯🇵Osaka, Japan
Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wrocławiu
🇵🇱Wrocław, Dolnośląskie, Poland
Uniwersytecki Szpital Kliniczny w Białymstoku
🇵🇱Białystok, Podlaskie, Poland
Miejski Szpital Zespolony w Olsztynie
🇵🇱Olsztyn, Warmińsko-mazurskie, Poland
Uniwersytecki Szpital Kliniczny w Poznaniu
🇵🇱Poznan, Wielkopolskie, Poland
Uniwersyteckie Centrum Kliniczne Warszawskiego Uniwersytetu Medycznego Centralny Szpital Kliniczny
🇵🇱Warsaw, Poland
Kardio Brynow
🇵🇱Katowice, Śląskie, Poland
CHUAC-Complejo Hospitalario Universitario A Coruña
🇪🇸A Coruña, A Coruña [LA Coruña], Spain
CHUS - Hospital Clinico Universitario
🇪🇸Santiago de Compostela, A Coruña [LA Coruña], Spain
Parc de Salut Mar - Hospital del Mar
🇪🇸Barcelona, Barcelona [barcelona], Spain
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Barcelona [barcelona], Spain
Hospital Universitari de Bellvitge
🇪🇸L'Hospitalet de Llobregat, Barcelona, Spain
Hospital de la Santa Creu i Sant Pau
🇪🇸Barcelona, Catalunya [cataluña], Spain
Hospital Universitario Ramón y Cajal
🇪🇸Madrid, Madrid, Comunidad DE, Spain
Hospital Universitario Puerta de Hierro Majadahonda
🇪🇸Majadahonda, Madrid, Comunidad DE, Spain
Hospital Clínico Universitario Virgen de la Arrixaca
🇪🇸El Palmar, Murcia, Región DE, Spain
Hospital Clinico de Valencia
🇪🇸Valencia, Valenciana, Comunitat, Spain
Hospital Universitario Virgen Nieves
🇪🇸Granada, Spain
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Hospital Universitario Central de Asturias
🇪🇸Oviedo, Spain
Hospital Universitario Virgen Del Rocio
🇪🇸Sevilla, Spain
Hospital General Universitario de Valencia
🇪🇸Valencia, Spain
Hospital Universitari i Politecnic La Fe
🇪🇸Valencia, Spain
Wycombe General Hospital
🇬🇧High Wycombe, Buckinghamshire, United Kingdom
Ninewells Hospital and Medical School
🇬🇧Dundee, Dundee CITY, United Kingdom
St. George's Hospital
🇬🇧London, England AND Wales, United Kingdom
Northwick Park Hospital
🇬🇧Harrow, London, CITY OF, United Kingdom
Glasgow Royal Infirmary
🇬🇧Glasgow, Scotland, United Kingdom
Barnet Hospital
🇬🇧Barnet, United Kingdom
Royal Papworth Hospital NHS Foundation Trust
🇬🇧Cambridge, United Kingdom
Golden Jubilee National Hospital
🇬🇧Clydebank, United Kingdom
Liverpool University Hospitals NHS Foundation Trust
🇬🇧Liverpool, United Kingdom
Northern General Hospital
🇬🇧Sheffield, United Kingdom
University Hospital of North Tees
🇬🇧Stockton-On-Tees, United Kingdom