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Purpose

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

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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).

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
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
Masking
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description
In the main cohort (Cohort A), Cohort C and Cohort D, 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 (Cohort B) 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 (Cohort B).

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Main cohort (Cohort A): ponsegromab low dose 		Participants will receive a low dose Q4W SC
  • Drug: Main cohort (Cohort A): Ponsegromab low dose
    Ponsegromab low dose subcutaneous injection
    Other names:
    • PF-06946860 low dose
Experimental
Main cohort (Cohort A): ponsegromab medium dose 		Participants will receive a medium dose Q4W SC
  • Drug: Main cohort (Cohort A): Ponsegromab medium dose
    Ponsegromab medium dose subcutaneous injection
    Other names:
    • PF-06946860 medium dose
Experimental
Main cohort (Cohort A): ponsegromab high dose 		Participants will receive a high dose Q4W SC
  • Drug: Main cohort (Cohort A): ponsegromab high dose
    Ponsegromab high dose subcutaneous injection
    Other names:
    • PF-06946860 high dose
Placebo Comparator
Main cohort (Cohort A): placebo 		matched placebo
  • Other: Main cohort (Cohort A): Matched placebo
    Matched placebo subcutaneous injection
    Other names:
    • Placebo
Experimental
Open-label, PK Cohort (Cohort B): ponsegromab low dose 		Participants will receive a low dose Q4W SC
  • Drug: Open-label, PK Cohort (Cohort B): ponsegromab low dose
    ponsegromab low dose subcutaneous injection
    Other names:
    • PF-06946860 low dose
Experimental
Open-label, PK Cohort (Cohort B): ponsegromab medium dose 		Participants will receive a medium dose Q4W SC
  • Drug: Open-label, PK Cohort (Cohort B): ponsegromab medium dose
    Ponsegromab medium dose subcutaneous injection
    Other names:
    • PF-06946860 medium dose
Experimental
Open-label, PK Cohort (Cohort B): ponsegromab high dose 		Participants will receive a high dose Q4W SC
  • Drug: Open-label, PK Cohort (Cohort B): ponsegromab high dose
    Ponsegromab high dose subcutaneous injection
    Other names:
    • PF-06946860 high dose
Experimental
Optional Cohort C: ponsegromab low dose 		Participants will receive a low dose Q4W SC
  • Drug: Optional Cohort C: Ponsegromab low dose
    Ponsegromab low dose subcutaneous injection
    Other names:
    • PF-06946860 low dose
Placebo Comparator
Optional Cohort C: placebo 		matched placebo
  • Other: Optional Cohort C: Matched placebo
    Matched placebo subcutaneous injection
    Other names:
    • Placebo
Experimental
Optional Cohort D: ponsegromab high dose 		Participants will receive a high dose Q4W SC
  • Drug: Optional Cohort D: Ponsegromab high dose
    Ponsegromab high dose subcutaneous injection
    Other names:
    • PF-06946860 high dose
Placebo Comparator
Optional Cohort D: placebo 		matched placebo
  • Other: Optional Cohort D: Matched placebo
    Matched placebo subcutaneous injection
    Other names:
    • Placebo

Recruiting Locations

MedStar Washington Hospital Center
Washington, District of Columbia 20010

More Details

Status
Recruiting
Sponsor
Pfizer

Study Contact

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

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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.