Heart failure MedDRA version: 20.0 Level: HLGT Classification code 10019280 Term: Heart failures System Organ Class: 10007541 - Cardiac disorders
Conditions
Sponsors
Pfizer Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Age and Sex: 1. Participants aged 18 years or older (or the minimum age of consent in accordance with local regulations) at screening. a. A female participant is eligible to participate if she is not pregnant or breastfeeding. b. To refer to Appendix 4 of Protocol for reproductive criteria for male (Section 10.4.1 of Protocol) and female (Section 10.4.2 of Protocol) participants. Disease Characteristics: 2. Clinical evidence of HF with each of the following criteria: a. LVEF =65 years) yes F.1.3.1 Number of subjects for this age range 218
Exclusion criteria
Exclusion criteria: Medical Conditions: 1. Acute decompensated HF within 1 month prior to SV1 or during the screening period. 2. 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. 3. History of heart transplantation, currently listed for heart transplant, current/planned mechanical circulatory support, or current/planned use of intravenous inotropes (eg, dobutamine, milrinone). 4. Acute coronary syndrome within 1 month prior to randomization. 5. 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. 6. Untreated indication for an implantable cardiac defibrillator or pacemaker to treat a cardiac rhythm abnormality (i.e, tachyarrhythmia or bradyarrhythmia). 7. History of allergic or anaphylactic reaction to any therapeutic or diagnostic monoclonal antibody (IgG protein) or molecules made of components of monoclonal antibody. 8. Other medical (eg, severe, uncorrected aortic stenosis; active malignancy) or psychiatric condition including recent (within the past year) or active suicidal ideation/behaviour or laboratory abnormality that may increase the risk of study participation or, in the investigator’s judgment, may limit life expectancy to less than 1 year and / or make the participant inappropriate for the study. 9. Current use of any prohibited concomitant medication(s). To refer to Section 6.9 of Protocol. 10. Previous administration with an investigational drug within 30 days (or as determined by the local requirement) or 5 half lives preceding the first dose of study intervention used in this study (whichever is longer). Treatment with an investigational biotherapeutic agent within 6 months or 5 half-lives (whichever is longer) of Day 1. 11. Previous exposure to ponsegromab in a prior clinical study. 12. Renal disease requiring ongoing dialysis. 13. 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). 14. Investigator site staff or Pfizer employees directly involved in the conduct of the study, site staff otherwise supervised by the investigator, and their respective family members. 15.Open-label, PK Cohort: At certain sites in the US and Canada, where permitted, participants who fail to qualify for the main cohort may be eligible for participation in a separate open-label, PK cohort.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the effect of ponsegromab versus placebo, on HF disease-specific health status in participants with HF.;Secondary Objective: Main Cohort: - To compare the effect of ponsegromab versus placebo on HF disease-specific overall health status in participants with HF. - To compare the effect of ponsegromab versus placebo on HF disease-specific health status in participants with HF. - To compare the effect of ponsegromab versus placebo on the physical function of participants with HF. - To compare the effect of ponsegromab versus placebo on fatigue reported by participants with HF. - To describe the safety and tolerability of ponsegromab in participants with HF. Open-Label PK Cohort: -To evaluate the safety and tolerability of ponsegromab in participants with HF and elevated circulating GDF-15 concentrations. Open-label, PK Cohort: At certain sites in the US and Canada, where permitted, participants who fail to qualify for the main cohort may be eligible for participation in a separate open-label, PK cohort. ;Primary end point(s): Change from baseline in KCCQ-23 CSS at Week 22.;Timepoint(s) of evaluation of this end point: At Week 22 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): For objective "To compare the effect of ponsegromab versus placebo on HF disease-specific overall health status in participants with HF": Change from baseline in KCCQ-23 OSS, TSS, and physical limitation at Week 22. For objective "To compare the effect of ponsegromab versus placebo on HF disease-specific health status in participants with HF": Responses as defined by a =5-point increase from baseline in KCCQ-23 CSS, OSS, TSS, and physical limitation at Week 22. For objective "To compare the effect of ponsegromab versus placebo on the physical function of participants with HF": Change from baseline in 6MWD at Week 22. For objective "To compare the effect of ponsegromab versus placebo on fatigue reported by participants with HF": Change from baseline in PROMIS Fatigue 7a at Week 22. For objective "To describe the safety and tolerability of ponsegromab in participants with HF": Incidence of TEAEs, TESAEs, abnormal laboratory results, and vital signs. For PK Open-Label PK Cohort secondary Objective "Incidence of TEAEs, TESAEs, abnormal laboratory results, and vital signs." Open-label, PK Cohort: At certain sites in the US and Canada, where permitted, participants who fail to qualify for the main cohort may be eligible for participation in a separate open-label, PK cohort.;Timepoint(s) of evaluation of this end point: Week 22 for all Main Cohort secondary endpoint except for the last one (To describe the safety and tolerability of ponsegromab in participants with HF) which will be evaluated throughout the trial as applicable. For Open-Label PK Cohort: throughout the trial. | — |
Countries
Australia, Canada, China, Czechia, Germany, Hungary, Japan, Poland, Spain, United Kingdom, United States
Contacts
Public ContactClinical Trials.gov Call Centre
Pfizer Inc.
Outcome results
None listed