Heart Failure
Conditions
Interventions
Experimental: Main cohort (Cohort A):ponsegromab low dose
Participants will receive a low dose Q4W SC
Experimental: Main cohort (Cohort A): ponsegromab medium dose
Participants will receive a medium
Sponsors
Kawai Norisuke
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: *Male and female participants aged 18 years or older -.Clinical evidence of HF with each of the following criteria: 1.LVEF =400 pg/mL at screening. *Serum GDF-15 concentration >=2000 pg/mL at screening. *Cohort D only: Serum GDF-15 concentration =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
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. 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. 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).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main cohort (Cohort A): Change from baseline in Kansas City Cardiomyopathy Questionnaire 23 Clinical Summary Score 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 [ Time Frame: baseline, 22 weeks ] | — |
Secondary
| Measure | Time frame |
|---|---|
| Main cohort (Cohort A): Change from baseline in Kansas City Cardiomyopathy Questionnaire 23 Overall Summary Score 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 [ Time Frame: baseline, 22 weeks ] Main cohort (Cohort A): Change from baseline in Kansas City Cardiomyopathy Questionnaire 23 Total Symptom Score 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 [ Time Frame: baseline, 22 weeks ] Main cohort (Cohort A): Change from baseline in Kansas City Cardiomyopathy Questionnaire 23 physical limitations domain 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 [ Time Frame: baseline, 22 weeks ] Main cohort (Cohort A): Responses as defined by a >=5 point increase from baseline in Kansas City Cardiomyopathy Questionnaire 23 Clinical Summary Score To compare the effect of ponsegromab versus placebo on HF disease-specific health status in participants with HF and elevated serum GDF-15 concentrations [ Time Frame: baseline, 22 weeks ] Main cohort (Cohort A): Responses as defined by a >=5 point increase from baseline in Overall Summary Score To compare the effect of ponsegromab versus placebo on HF disease-specific health status in participants with HF and elevated serum GDF-15 concentrations [ Time Frame: baseline, 22 weeks ] Main cohort (Cohort A): Responses as defined by a >=5 point increase from baseline in Total Symptom Score To compare the effect of ponsegromab versus placebo on HF disease-specific health status in participants with HF and elevated serum GDF-15 concentrations [ Time Frame: baseline, 22 weeks ] Main cohort (Cohort A): Responses as defined by a >=5 point increase from baseline in physical limitation To compare | — |
Countries
Australia, Canada, China, Czechia, Germany, Hungary, Japan, Poland, Spain, United Kingdom, United States
Contacts
Public ContactClinical Trials Information Desk
Pfizer R&D Japan G.K.
Outcome results
None listed