A Study of Ponsegromab in People With Heart Failure

JRCT ID: jRCT2051220111

Registered date:27/10/2022

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Heart Failure
• Date of first enrollment: 25/11/2022
• Target sample size: 416
• Countries of recruitment: Australia,Japan,Canada,Japan,China,Japan,Czechia,Japan,Hungary,Japan,Poland,Japan,Spain,Japan,United Kingdom,Japan,United States,Japan
• Study type: Interventional

Intervention(s)

Experimental: ponsegromab low dose
Participants will receive a low dose Q4W SC

Experimental: ponsegromab medium dose
Participants will receive a medium dose Q4W SC

Experimental: ponsegromab high dose
Participants will receive a high dose Q4W SC

Placebo Comparator: placebo
matched placebo

Outcome(s)

Primary Outcome

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include 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.
2.NYHA class II-IV at screening.
3.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 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.

Exclude 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).

Related Information

• Primary Sponsor: Kawai Norisuke
• Secondary ID(s): NCT05492500