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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05492500
Recruitment Status : Recruiting
First Posted : August 8, 2022
Last Update Posted : April 30, 2024
Sponsor:
Collaborator:
Thrombolysis In Myocardial Infarction (TIMI)
Information provided by (Responsible Party):
Pfizer

Study Description
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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.


Condition or disease Intervention/treatment Phase
Heart Failure Drug: Main cohort: Ponsegromab low dose Drug: Main cohort: Ponsegromab medium dose Drug: Main cohort: ponsegromab high dose Other: Main cohort: Matched placebo Drug: Open-label, PK Cohort: ponsegromab low dose Drug: Open-label, PK Cohort: ponsegromab medium dose Drug: Open-label, PK Cohort: ponsegromab high dose Phase 2

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 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.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 416 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

In the main cohort, 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 a separate open-label, PK cohort, 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.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

In the main cohort, 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 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.
Primary Purpose: Supportive Care
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
Actual Study Start Date : September 26, 2022
Estimated Primary Completion Date : March 30, 2025
Estimated Study Completion Date : June 7, 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Heart Failure

Arms and Interventions
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Arm Intervention/treatment
Experimental: Main cohort: ponsegromab low dose
Participants will receive a low dose Q4W SC
 Drug: Main cohort: Ponsegromab low dose
Ponsegromab low dose subcutaneous injection
Other Name: PF-06946860 low dose
Experimental: Main cohort: ponsegromab medium dose
Participants will receive a medium dose Q4W SC
 Drug: Main cohort: Ponsegromab medium dose
Ponsegromab medium dose subcutaneous injection
Other Name: PF-06946860 medium dose
Experimental: Main cohort: ponsegromab high dose
Participants will receive a high dose Q4W SC
 Drug: Main cohort: ponsegromab high dose
Ponsegromab high dose subcutaneous injection
Other Name: PF-06946860 high dose
Placebo Comparator: Main cohort: placebo
matched placebo
 Other: Main cohort: Matched placebo
Matched placebo subcutaneous injection
Other Name: Placebo
Experimental: Open-label, PK Cohort: ponsegromab low dose
Participants will receive a low dose Q4W SC
 Drug: Open-label, PK Cohort: ponsegromab low dose
ponsegromab low dose subcutaneous injection
Other Name: PF-06946860 low dose
Experimental: Open-label, PK Cohort: ponsegromab medium dose
Participants will receive a medium dose Q4W SC
 Drug: Open-label, PK Cohort: ponsegromab medium dose
Ponsegromab medium dose subcutaneous injection
Other Name: PF-06946860 medium dose
Experimental: Open-label, PK Cohort: ponsegromab high dose
Participants will receive a high dose Q4W SC
 Drug: Open-label, PK Cohort: ponsegromab high dose
Ponsegromab high dose subcutaneous injection
Other Name: PF-06946860 high dose


Outcome Measures
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Primary Outcome Measures :
  1. Main cohort: Change from baseline in Kansas City Cardiomyopathy Questionnaire 23 Clinical Summary Score [ Time Frame: baseline, 22 weeks ]
    To compare the effect of ponsegromab versus placebo, on heart failure disease-specific health status in participants with heart failure


Secondary Outcome Measures :
  1. Main cohort: Change from baseline in Kansas City Cardiomyopathy Questionnaire 23 Overall Summary Score [ Time Frame: baseline, 22 weeks ]
    To compare the effect of ponsegromab versus placebo on HF disease-specific overall health status in participants with HF

  2. Main cohort: Change from baseline in Kansas City Cardiomyopathy Questionnaire 23 Total Symptom Score [ Time Frame: baseline, 22 weeks ]
    To compare the effect of ponsegromab versus placebo on HF disease-specific overall health status in participants with HF

  3. Main cohort: Change from baseline in Kansas City Cardiomyopathy Questionnaire 23 physical limitations domain [ Time Frame: baseline, 22 weeks ]
    To compare the effect of ponsegromab versus placebo on HF disease-specific overall health status in participants with HF

  4. Main cohort: Responses as defined by a ≥5 point increase from baseline in Kansas City Cardiomyopathy Questionnaire 23 Clinical Summary Score [ Time Frame: baseline, 22 weeks ]
    To compare the effect of ponsegromab versus placebo on HF disease-specific health status in participants with HF

  5. Main cohort: Responses as defined by a ≥5 point increase from baseline in Overall Summary Score [ Time Frame: baseline, 22 weeks ]
    To compare the effect of ponsegromab versus placebo on HF disease-specific health status in participants with HF

  6. Main cohort: Responses as defined by a ≥5 point increase from baseline in Total Symptom Score [ Time Frame: baseline, 22 weeks ]
    To compare the effect of ponsegromab versus placebo on HF disease-specific health status in participants with HF

  7. Main cohort: Responses as defined by a ≥5 point increase from baseline in physical limitation [ Time Frame: baseline, 22 weeks ]
    To compare the effect of ponsegromab versus placebo on HF disease-specific health status in participants with HF

  8. Main cohort: Change from baseline in 6-Minute Walk Distance [ Time Frame: baseline, 22 weeks ]
    To compare the effect of ponsegromab versus placebo on the physical function of participants with HF

  9. 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 [ Time Frame: baseline, 22 weeks ]
    To compare the effect of ponsegromab versus placebo on fatigue reported by participants with HF

  10. Main cohort: Incidence of treatment-emergent adverse events [ Time Frame: 32 weeks ]
    To describe the safety and tolerability of ponsegromab in participants with HF

  11. Main cohort: Incidence of treatment-emergent serious adverse events [ Time Frame: 32 weeks ]
    To describe the safety and tolerability of ponsegromab in participants with HF

  12. Main cohort: Incidence of abnormal laboratory results [ Time Frame: 32 weeks ]
    To describe the safety and tolerability of ponsegromab in participants with HF

  13. Main cohort: Incidence of abnormal vital signs [ Time Frame: 32 weeks ]
    To describe the safety and tolerability of ponsegromab in participants with HF

  14. Open-Label, PK Cohort: Incidence of treatment-emergent adverse events [ Time Frame: 22 weeks ]
    To describe the safety and tolerability of ponsegromab in participants with HF

  15. Open-Label, PK Cohort: Incidence of treatment-emergent serious adverse events [ Time Frame: 22 weeks ]
    To describe the safety and tolerability of ponsegromab in participants with HF

  16. Open-Label, PK Cohort: Incidence of abnormal laboratory results [ Time Frame: 22 weeks ]
    To describe the safety and tolerability of ponsegromab in participants with HF

  17. Open-Label, PK Cohort: Incidence of abnormal vital signs [ Time Frame: 22 weeks ]
    To describe the safety and tolerability of ponsegromab in participants with HF


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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. 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).
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05492500


Contacts
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Contact: Pfizer CT.gov Call Center 1-800-718-1021 ClinicalTrials.gov_Inquiries@pfizer.com

Locations
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Sponsors and Collaborators
Pfizer
Thrombolysis In Myocardial Infarction (TIMI)
Investigators
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Study Director: Pfizer CT.gov Call Center Pfizer
More Information
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Additional Information:

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Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT05492500    
Other Study ID Numbers: C3651011
2022-001809-50 ( EudraCT Number )
First Posted: August 8, 2022    Key Record Dates
Last Update Posted: April 30, 2024
Last Verified: April 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: 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.
URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Pfizer:
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
Additional relevant MeSH terms:
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Heart Failure
Heart Diseases
Cardiovascular Diseases