Clinical trial NCT05492500: A Study of Ponsegromab in People With Heart Failure
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
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
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
Collaborators: name: The TIMI Study Group
First posted: 2022-08-08
Enrollment: 455
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: SUPPORTIVE_CARE

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.

Eligibility criteria: Inclusion Criteria:

* Male and female participants aged 18 years or older

  -. Clinical evidence of HF with each of the following criteria:
  1. LVEF \<50% on most recent measurement, within 12 months of screening. Note: An assessment of LVEF in the prior 12 months is not required in situations where LVEF has been persistently \<50% on prior assessments obtained at least 3 months apart (including the most recent measurement).
  2. NYHA class II-IV at screening.
  3. NT-proBNP ≥400 pg/mL at screening (Note: Does not apply to open-label, PK Cohort \[Cohort B\]).
* Serum GDF-15 concentration ≥2000 pg/mL at screening.
* Cohort D only: Serum GDF-15 concentration \<2000 pg/mL at screening.
* KCCQ-23 CSS \<75 at screening (Note: Does not apply to open-label, PK Cohort \[Cohort B\]).
* Evidence of cachexia or fatigue or functional impairment, as demonstrated by at least one of the following at screening (Note: Does not apply to open-label, PK Cohort \[Cohort B\]):

  1. Non-edematous unintentional weight loss ≥5% in the last 6 months or current BMI \<20 kg/m2, associated with subjective fatigue or anorexia; or
  2. Fatigue at least 3 times per week AND at least moderately bothersome fatigue in the past 2 weeks based on the KCCQ-23 administered at screening; or
  3. A score of \<60 on the Physical Limitations Domain of the KCCQ 23 administered at screening.

Exclusion Criteria:

* Acute decompensated HF within 1 month prior to Screening Visit 1 or during the screening period.
* Implantation of a cardiac resynchronization therapy device or valve repair or replacement within 3 months prior to randomization or intent to do so during the trial.

For the open-label, PK cohort (Cohort B) only: implantation of a cardiac resynchronization therapy device more than 1 month prior to randomization is permitted.

* History of heart transplantation, currently listed for heart transplant, current/planned mechanical circulatory support, or current/planned use of intravenous inotropes (eg, dobutamine, milrinone).
* Acute coronary syndrome within 1 month prior to randomization.
* Coronary revascularization (percutaneous coronary intervention or coronary artery bypass grafting) within 3 months prior to randomization or intent to undergo coronary revascularization during the trial.

For the open-label, PK cohort (Cohort B) only: coronary revascularization more than 1 month prior to randomization is permitted.

* Untreated indication for an implantable cardiac defibrillator or pacemaker to treat a cardiac rhythm abnormality (ie, tachyarrhythmia or bradyarrhythmia).
* Previous administration with an investigational product (drug or vaccine) within 30 days (or as determined by the local requirement) or 5 half lives (whichever is longer) preceding the first dose of study intervention used in this study. Treatment with an investigational biologic agent within 6 months or 5 half-lives (whichever is longer) of Day 1.
* Previous exposure to ponsegromab in a prior clinical study.
* Renal disease requiring ongoing dialysis.
* Cirrhosis with evidence of portal hypertension not due to HF, or the following LFT abnormalities at the time of screening, confirmed by a repeat test if deemed necessary: AST or ALT level ≥ 3 x ULN, or total bilirubin level ≥ 2 x ULN (unless history of Gilbert's syndrome).

Primary outcomes:
measure: Main cohort (Cohort A): Change from baseline in Kansas City Cardiomyopathy Questionnaire 23 Clinical Summary Score
timeFrame: baseline, 22 weeks
Secondary outcomes:
measure: Main cohort (Cohort A): Change from baseline in Kansas City Cardiomyopathy Questionnaire 23 Overall Summary Score
timeFrame: baseline, 22 weeks
measure: Main cohort (Cohort A): Change from baseline in Kansas City Cardiomyopathy Questionnaire 23 Total Symptom Score
timeFrame: baseline, 22 weeks
measure: Main cohort (Cohort A): Change from baseline in Kansas City Cardiomyopathy Questionnaire 23 physical limitations domain
timeFrame: baseline, 22 weeks
measure: Main cohort (Cohort A): Responses as defined by a ≥5 point increase from baseline in Kansas City Cardiomyopathy Questionnaire 23 Clinical Summary Score
timeFrame: baseline, 22 weeks
measure: Main cohort (Cohort A): Responses as defined by a ≥5 point increase from baseline in Overall Summary Score
timeFrame: baseline, 22 weeks
measure: Main cohort (Cohort A): Responses as defined by a ≥5 point increase from baseline in Total Symptom Score
timeFrame: baseline, 22 weeks
measure: Main cohort (Cohort A): Responses as defined by a ≥5 point increase from baseline in physical limitation
timeFrame: baseline, 22 weeks
measure: Main cohort (Cohort A): Change from baseline in 6-Minute Walk Distance
timeFrame: baseline, 22 weeks
measure: 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
timeFrame: baseline, 22 weeks
measure: Main cohort (Cohort A)/Cohort C/Cohort D: Incidence of treatment-emergent adverse events
timeFrame: 32 weeks
measure: Main cohort (Cohort A)/Cohort C/Cohort D: Incidence of treatment-emergent serious adverse events
timeFrame: 32 weeks
measure: Main cohort (Cohort A)/Cohort C/Cohort D: Incidence of abnormal laboratory results
timeFrame: 32 weeks
measure: Main cohort (Cohort A)/Cohort C/Cohort D: Incidence of abnormal vital signs
timeFrame: 32 weeks
measure: Open-Label, PK Cohort (Cohort B): Incidence of treatment-emergent adverse events
timeFrame: 22 weeks
measure: Open-Label, PK Cohort (Cohort B): Incidence of treatment-emergent serious adverse events
timeFrame: 22 weeks
measure: Open-Label, PK Cohort (Cohort B): Incidence of abnormal laboratory results
timeFrame: 22 weeks
measure: Open-Label, PK Cohort (Cohort B): Incidence of abnormal vital signs
timeFrame: 22 weeks
Other outcomes:
Locations:
city: Fairhope
country: United States
facility: Eastern shore Research Institute LLC
state: Alabama
city: Los Angeles
country: United States
facility: Keck Medical Center of USC
state: California
city: Washington
country: United States
facility: MedStar Washington Hospital Center
state: District of Columbia
city: Atlanta
country: United States
facility: Emory University School of Medicine-Grady Campus
state: Georgia
city: Hazel Crest
country: United States
facility: Chicago Medical Research
state: Illinois
city: Richmond
country: United States
facility: Reid Physician Associates
state: Indiana
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Traverse City
country: United States
facility: Traverse Heart & Vascular
state: Michigan
city: Minneapolis
country: United States
facility: M Health Fairview Clinics and Surgery Center
state: Minnesota
city: Minneapolis
country: United States
facility: M Health Fairview University of Minnesota Investigational Drug Services
state: Minnesota
city: Minneapolis
country: United States
facility: M Health Fairview University of Minnesota Medical Center-East Bank
state: Minnesota
city: Minneapolis
country: United States
facility: University of Minnesota/Lillehei Clinical Research Unit
state: Minnesota
city: Kansas City
country: United States
facility: Saint Luke's Hospital of Kansas City
state: Missouri
city: Saint Louis
country: United States
facility: Washington University in St. Louis Center for Outpatient Health (COH)
state: Missouri
city: Saint Louis
country: United States
facility: Washington University in St. Louis Center for Advanced Medicine (CAM)
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Teaneck
country: United States
facility: Holy Name Medical Center
state: New Jersey
city: Chapel Hill
country: United States
facility: University of North Carolina Medical Center
state: North Carolina
city: Chapel Hill
country: United States
facility: Clinical and Translational Research Center
state: North Carolina
city: Oklahoma City
country: United States
facility: South Oklahoma Heart Research, LLC
state: Oklahoma
city: Dallas
country: United States
facility: Texas Health Heart & Vascular Specialist (THHVS) #18760
state: Texas
city: Concord
country: Australia
facility: Concord Repatriation General Hospital
state: New South Wales
city: Brisbane
country: Australia
facility: Core Research Group
state: Queensland
city: Chermside
country: Australia
facility: The Prince Charles Hospital
state: Queensland
city: Elizabeth Vale
country: Australia
facility: Lyell McEwin Hospital
state: South Australia
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
city: New Westminster
country: Canada
facility: Fraser Clinical Trials Inc
state: British Columbia
city: Halifax
country: Canada
facility: QEII Health Sciences Centre - Victoria General Site
state: Nova Scotia
city: Cambridge
country: Canada
facility: Saul Vizel Professional Medicine Corporation dba Vizel Cardiac Research
state: Ontario
city: London
country: Canada
facility: University Hospital - London Health Sciences Centre
state: Ontario
city: North York
country: Canada
facility: North York Diagnostic and Cardiac Centre
state: Ontario
city: Oshawa
country: Canada
facility: Private Practice - Dr. James Cha
state: Ontario
city: Peterborough
country: Canada
facility: Kawartha Cardiology Clinical Trials
state: Ontario
city: Toronto
country: Canada
facility: Corcare
state: Ontario
city: Toronto
country: Canada
facility: Unity Health Toronto, St. Michael's Hospital
state: Ontario
city: Winchester
country: Canada
facility: Community Care Building
state: Ontario
city: Winchester
country: Canada
facility: Winchester District Memorial Hospital
state: Ontario
city: Montreal
country: Canada
facility: Institut de Cardiologie de Montreal
state: Quebec
city: Montréal
country: Canada
facility: Centre Hospitalier de l'Université de Montréal
state: Quebec
city: Rimouski
country: Canada
facility: Centre intégré de santé et de services sociaux du Bas Saint-Laurent- Hôpital régional de Rimouski
state: Quebec
city: Saint-Jean-sur-Richelieu
country: Canada
facility: CardioVasc HR Inc
state: Quebec
city: Terrebonne
country: Canada
facility: Centre intégré de santé et de services sociaux de Lanaudière - Hopital Pierre-Le Gardeur.
state: Quebec
city: Trois-Rivieres
country: Canada
facility: Diex Recherche Trois-Rivieres
state: Quebec
city: Guangzhou
country: China
facility: Guangdong Provincial People's Hospital
state: Guangdong
city: Guangzhou
country: China
facility: The First Affiliated Hospital, Sun Yat-sen University
state: Guangdong
city: Changsha
country: China
facility: The Second Xiangya Hospital of Central South University
state: Hunan
city: Hengyang
country: China
facility: The First Affiliated Hospital of University of South China
state: Hunan
city: Changchun
country: China
facility: China-Japan Union Hospital
state: Jilin
city: Xi'an
country: China
facility: The First Affiliated Hospital of Xi'an Jiaotong University
state: Shaanxi
city: Jinan
country: China
facility: Qilu Hospital of Shandong University
state: Shandong
city: Shanghai
country: China
facility: Zhongshan Hospital,Fudan University
state: Shanghai
city: Yuncheng
country: China
facility: Yuncheng Central Hospital
state: Shanxi
city: Tianjin
country: China
facility: Tianjin People' s Hospital
state: Tianjin
city: Beijing
country: China
facility: Peking University First Hospital
city: Brno
country: Czechia
facility: Fakultni Nemocnice u sv. Anny v Brne
state: Jihomoravský KRAJ
city: Jaroměř
country: Czechia
facility: EDUMED - Jaroměř
state: Náchod
city: Prague
country: Czechia
facility: Institut Klinicke a Experimentalni Mediciny
state: Praha 4
city: Praha 10
country: Czechia
facility: Fakultni nemocnice Kralovske Vinohrady
city: Praha 2
country: Czechia
facility: Vseobecna fakultni nemocnice v Praze
city: Praha 6
country: Czechia
facility: Ustredni vojenska nemocnice
city: Frankfurt
country: Germany
facility: Universitätsklinikum Frankfurt Goethe-Universität
state: Hessen
city: Göttingen
country: Germany
facility: Universitätsmedizin Göttingen - Georg-August-Universität
state: Niedersachsen
city: Bad Oeynhausen
country: Germany
facility: Herz - und Diabeteszentrum Nordrhein - Westfalen, Bad Oeynhausen
state: Nordrhein-westfalen
city: Dresden
country: Germany
facility: Hausärztlich-Kardiologisches MVZ am Felsenkeller GmbH/Zentrum für klinische Studien
state: Sachsen
city: Jena
country: Germany
facility: Universitätsklinikum Jena
state: Thuringia
city: Jena
country: Germany
facility: Universitätsklinikum Jena
state: Thüringen
city: Pécs
country: Hungary
facility: Pécsi Tudományegyetem Klinikai Központ
state: Baranya
city: Békéscsaba
country: Hungary
facility: Private Practice - Dr. Lakatos Ferenc
state: Békés
city: Mosonmagyaróvár
country: Hungary
facility: TaNa Med
state: Győr-moson-sopron
city: Nyiregyhaza
country: Hungary
facility: Medifarma 98 Kft
state: Nyíregyháza
city: Kaposvár
country: Hungary
facility: Somogy Vármegyei Kaposi Mór Oktató Kórház
state: Somogy
city: Budapest
country: Hungary
facility: Dél-Pesti Centrumkórház Orszagos Hematologiai es Infektologiai Intezet
city: Budapest
country: Hungary
facility: Semmelweis Egyetem
city: Nagykanizsa
country: Hungary
facility: Kanizsai Dorottya Korhaz
city: Amagasaki
country: Japan
facility: Hyogo Prefectural Amagasaki General Medical Center
state: Hyogo
city: Himeji
country: Japan
facility: Hyogo Prefectural Harima-Himeji General Medical Center
state: Hyogo
city: Takarazuka
country: Japan
facility: Higashi Takarazuka Satoh Hospital
state: Hyogo
city: Morioka
country: Japan
facility: Iwate Prefectural Central Hospital
state: Iwate
city: Sendai
country: Japan
facility: National Hospital Organization Sendai Medical Center
state: Miyagi
city: Kishiwada
country: Japan
facility: Kishiwada Tokushukai Hospital
state: Osaka
city: Suita
country: Japan
facility: National Cerebral and Cardiovascular Center
state: Osaka
city: Wako
country: Japan
facility: National Hospital Organization Saitama Hospital
state: Saitama
city: Shinjuku-ku
country: Japan
facility: Keio University Hospital
state: Tokyo
city: Osaka
country: Japan
facility: Osaka General Medical Center
city: Wrocław
country: Poland
facility: Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wrocławiu
state: Dolnośląskie
city: Białystok
country: Poland
facility: Uniwersytecki Szpital Kliniczny w Białymstoku
state: Podlaskie
city: Olsztyn
country: Poland
facility: Miejski Szpital Zespolony w Olsztynie
state: Warmińsko-mazurskie
city: Poznan
country: Poland
facility: Uniwersytecki Szpital Kliniczny w Poznaniu
state: Wielkopolskie
city: Lodz
country: Poland
facility: SPZOZ Centralny Szpital Kliniczny Uniwersytetu Medycznego w Lodzi
city: Tychy
country: Poland
facility: Polsko Amerykanskie Kliniki Serca
city: Warsaw
country: Poland
facility: Uniwersyteckie Centrum Kliniczne Warszawskiego Uniwersytetu Medycznego Centralny Szpital Kliniczny
city: Katowice
country: Poland
facility: Kardio Brynow
state: Śląskie
city: A Coruña
country: Spain
facility: CHUAC-Complejo Hospitalario Universitario A Coruña
state: A Coruña [LA Coruña]
city: Santiago de Compostela
country: Spain
facility: CHUS - Hospital Clinico Universitario
state: A Coruña [LA Coruña]
city: Barcelona
country: Spain
facility: Parc de Salut Mar - Hospital del Mar
state: Barcelona [barcelona]
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
state: Barcelona [barcelona]
city: L'Hospitalet de Llobregat
country: Spain
facility: Hospital Universitari de Bellvitge
state: Barcelona
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
state: Catalunya [cataluña]
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
state: Madrid, Comunidad DE
city: Majadahonda
country: Spain
facility: Hospital Universitario Puerta de Hierro Majadahonda
state: Madrid, Comunidad DE
city: El Palmar
country: Spain
facility: Hospital Clínico Universitario Virgen de la Arrixaca
state: Murcia, Región DE
city: Valencia
country: Spain
facility: Hospital Clinico de Valencia
state: Valenciana, Comunitat
city: Granada
country: Spain
facility: Hospital Universitario Virgen Nieves
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Málaga
country: Spain
facility: Hospital Universitario Virgen de la Victoria
city: Oviedo
country: Spain
facility: Hospital Universitario Central de Asturias
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Del Rocio
city: Valencia
country: Spain
facility: Hospital General Universitario de Valencia
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe
city: High Wycombe
country: United Kingdom
facility: Wycombe General Hospital
state: Buckinghamshire
city: Dundee
country: United Kingdom
facility: Ninewells Hospital and Medical School
state: Dundee CITY
city: London
country: United Kingdom
facility: St. George's Hospital
state: England AND Wales
city: Harrow
country: United Kingdom
facility: Northwick Park Hospital
state: London, CITY OF
city: Glasgow
country: United Kingdom
facility: Glasgow Royal Infirmary
state: Scotland
city: Barnet
country: United Kingdom
facility: Barnet Hospital
city: Cambridge
country: United Kingdom
facility: Royal Papworth Hospital NHS Foundation Trust
city: Clydebank
country: United Kingdom
facility: Golden Jubilee National Hospital
city: Lincoln
country: United Kingdom
facility: Lincoln County Hospital
city: Liverpool
country: United Kingdom
facility: Liverpool University Hospitals NHS Foundation Trust
city: Sheffield
country: United Kingdom
facility: Northern General Hospital
city: Stockton-On-Tees
country: United Kingdom
facility: University Hospital of North Tees
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: