The trial is taking place at:
K

Kawartha Cardiology Clinical Trials | Peterborough, Canada

Veeva-enabled site

A Study of Ponsegromab in People With Heart Failure (GARDEN TIMI 74)

Pfizer logo

Pfizer

Status and phase

Enrolling
Phase 2

Conditions

Heart Failure

Treatments

Drug: Open-label, PK Cohort: ponsegromab medium dose
Drug: Open-label, PK Cohort: ponsegromab low dose
Drug: Open-label, PK Cohort: ponsegromab high dose
Drug: Main cohort: Ponsegromab medium dose
Other: Main cohort: Matched placebo
Drug: Main cohort: Ponsegromab low dose
Drug: Main cohort: ponsegromab high dose

Study type

Interventional

Funder types

Industry
Other

Identifiers

NCT05492500
2022-001809-50 (EudraCT Number)
C3651011
2023-509747-27-00 (Registry Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment

416 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

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.
  • 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:

  • 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.

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).

Trial design

Primary purpose

Supportive Care

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Quadruple Blind

416 participants in 7 patient groups, including a placebo group

Main cohort: ponsegromab low dose
Experimental group
Description:
Participants will receive a low dose Q4W SC
Treatment:
Drug: Main cohort: Ponsegromab low dose
Main cohort: ponsegromab medium dose
Experimental group
Description:
Participants will receive a medium dose Q4W SC
Treatment:
Drug: Main cohort: Ponsegromab medium dose
Main cohort: ponsegromab high dose
Experimental group
Description:
Participants will receive a high dose Q4W SC
Treatment:
Drug: Main cohort: ponsegromab high dose
Main cohort: placebo
Placebo Comparator group
Description:
matched placebo
Treatment:
Other: Main cohort: Matched placebo
Open-label, PK Cohort: ponsegromab low dose
Experimental group
Description:
Participants will receive a low dose Q4W SC
Treatment:
Drug: Open-label, PK Cohort: ponsegromab low dose
Open-label, PK Cohort: ponsegromab medium dose
Experimental group
Description:
Participants will receive a medium dose Q4W SC
Treatment:
Drug: Open-label, PK Cohort: ponsegromab medium dose
Open-label, PK Cohort: ponsegromab high dose
Experimental group
Description:
Participants will receive a high dose Q4W SC
Treatment:
Drug: Open-label, PK Cohort: ponsegromab high dose

Trial contacts and locations

135

Loading...

Central trial contact

Pfizer CT.gov Call Center

Data sourced from clinicaltrials.gov

Clinical trials

Find clinical trialsTrials by location
© Copyright 2024 Veeva Systems