A Study of Ponsegromab in People With Heart Failure

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 the last 12 months).
NYHA class II-IV at screening.
NT-proBNP ≥400 pg/mL at screening.
Serum GDF-15 concentration ≥2000 pg/mL at screening.
KCCQ-23 CSS <75 at screening.

Evidence of cachexia or fatigue or functional impairment, as demonstrated by at least one of the following:

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; 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 randomization.
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, or planned mechanical circulatory support.
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
Renal disease requiring dialysis.
Cirrhosis with evidence of portal hypertension not due to HF