A PHASE 2, DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED, 4-ARM STUDY TO INVESTIGATE SYMPTOMS, FUNCTION, HEALTH-RELATED QUALITY OF LIFE AND SAFETY WITH REPEATED SUBCUTANEOUS ADMINISTRATION OF PONSEGROMAB VERSUS PLACEBO IN ADULT PARTICIPANTS WITH HEART FAILURE
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- Pfizer
- 入组人数
- 455
- 试验地点
- 122
- 主要终点
- Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ)-23 - Clinical Summary Score (CSS) at Week 22: Cohort A, Ponsegromab 300 mg Versus Placebo
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Supportive Care
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
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).
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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 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).
- •NYHA class II-IV at screening.
- •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]):
- •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 based on the KCCQ-23 administered at screening; or
- •A score of <60 on the Physical Limitations Domain of the KCCQ 23 administered at screening.
排除标准
- •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
- •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).
研究组 & 干预措施
Open-label, PK Cohort (Cohort B): ponsegromab medium dose
Participants will receive a medium dose Q4W SC
干预措施: Open-label, PK Cohort (Cohort B): ponsegromab medium dose (Drug)
Main cohort (Cohort A): ponsegromab low dose
Participants will receive a low dose Q4W SC
干预措施: Main cohort (Cohort A): Ponsegromab low dose (Drug)
Main cohort (Cohort A): ponsegromab medium dose
Participants will receive a medium dose Q4W SC
干预措施: Main cohort (Cohort A): Ponsegromab medium dose (Drug)
Main cohort (Cohort A): ponsegromab high dose
Participants will receive a high dose Q4W SC
干预措施: Main cohort (Cohort A): ponsegromab high dose (Drug)
Main cohort (Cohort A): placebo
matched placebo
干预措施: Main cohort (Cohort A): Matched placebo (Other)
Open-label, PK Cohort (Cohort B): ponsegromab low dose
Participants will receive a low dose Q4W SC
干预措施: Open-label, PK Cohort (Cohort B): ponsegromab low dose (Drug)
Open-label, PK Cohort (Cohort B): ponsegromab high dose
Participants will receive a high dose Q4W SC
干预措施: Open-label, PK Cohort (Cohort B): ponsegromab high dose (Drug)
Optional Cohort C: ponsegromab low dose
Participants will receive a low dose Q4W SC
干预措施: Optional Cohort C: Ponsegromab low dose (Drug)
Optional Cohort C: placebo
matched placebo
干预措施: Optional Cohort C: Matched placebo (Other)
Optional Cohort D: ponsegromab high dose
Participants will receive a high dose Q4W SC
干预措施: Optional Cohort D: Ponsegromab high dose (Drug)
Optional Cohort D: placebo
matched placebo
干预措施: Optional Cohort D: Matched placebo (Other)
结局指标
主要结局
Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ)-23 - Clinical Summary Score (CSS) at Week 22: Cohort A, Ponsegromab 300 mg Versus Placebo
时间窗: Baseline [the last measurement on study Day 1], Week 22
KCCQ is a self-reported 23-item questionnaire that assessed health related quality of life (HRQL) in participants with heart failure (HF) over the past 2 weeks. KCCQ quantifies 7 domains: physical limitations (6 items), symptom stability (1 item), symptom frequency (4 items), symptom burden (3 items), self-efficacy (2 items), quality of life (3 items) and social limitations (4 items). Scores were generated for each domain and scaled from 0 (worst status) to 100 (best possible status). KCCQ total symptom score (TSS): mean of domains- symptom frequency and symptom burden; and was transformed to a single score which ranged from 0 (worst) to 100 (best possible status). KCCQ-23-CSS: mean of the TSS and physical limitation domain score; and was transformed to a single score which ranged from 0 (worst) to 100 (best possible status), where higher KCCQ-23-CSS signified better health status.
次要结局
- Change From Baseline in KCCQ-23 CSS at Week 22: Cohort A(Baseline [the last measurement on study Day 1], Week 22)
- Change From Baseline in KCCQ-23-Overall Summary Score (OSS) at Week 22: Cohort A, Ponsegromab 300 mg Versus Placebo(Baseline [the last measurement on study Day 1], Week 22)
- Change From Baseline in KCCQ-23 OSS at Week 22: Cohort A(Baseline [the last measurement on study Day 1], Week 22)
- Change From Baseline in KCCQ-23-TSS at Week 22: Cohort A, Ponsegromab 300 mg Versus Placebo(Baseline [the last measurement on study Day 1], Week 22)
- Change From Baseline in KCCQ-23 TSS at Week 22: Cohort A(Baseline [the last measurement on study Day 1], Week 22)
- Change From Baseline in KCCQ-23 Physical Limitation Score at Week 22: Cohort A, Ponsegromab 300 mg Versus Placebo(Baseline [the last measurement on study Day 1], Week 22)
- Change From Baseline in KCCQ-23 Physical Limitation Score at Week 22: Cohort A(Baseline [the last measurement on study Day 1], Week 22)
- Percentage of Participants With >= 5-Point Increase From Baseline in KCCQ-23-CSS at Week 22: Cohort A, Ponsegromab 300 mg Versus Placebo(Week 22)
- Percentage of Participants With >= 5-Point Increase From Baseline in KCCQ-23 CSS Score at Week 22: Cohort A(Week 22)
- Percentage of Participants With >= 5-Point Increase From Baseline in KCCQ-23 OSS Score at Week 22: Cohort A, Ponsegromab 300 mg Versus Placebo(Week 22)
- Percentage of Participants With >= 5-Point Increase From Baseline in KCCQ-23 OSS Score at Week 22: Cohort A(Week 22)
- Percentage of Participants With >= 5-Point Increase From Baseline in KCCQ-23 TSS Score at Week 22: Cohort A, Ponsegromab 300 mg Versus Placebo(Week 22)
- Percentage of Participants With >= 5-Point Increase From Baseline in KCCQ-23 TSS Score at Week 22: Cohort A(Week 22)
- Percentage of Participants With >= 5-Point Increase From Baseline in KCCQ-23 PL Score at Week 22: Cohort A, Ponsegromab 300 mg Versus Placebo(Week 22)
- Percentage of Participants With >= 5-Point Increase From Baseline in KCCQ-23 PL Score at Week 22: Cohort A(Week 22)
- Change From Baseline in 6-Minute Walk Distance (6MWD) at Week 22: Cohort A, Ponsegromab 300 mg Versus Placebo(Baseline [the last measurement on study Day 1], Week 22)
- Change From Baseline in 6MWD at Week 22: Cohort A(Baseline [the last measurement on study Day 1], Week 22)
- Change From Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue (Version 7a) at Week 22: Cohort A, Ponsegromab 300 mg Versus Placebo(Baseline [the last measurement on study Day 1], Week 22)
- Change From Baseline in PROMIS Fatigue (Version 7a) at Week 22: Cohort A(Baseline [the last measurement on study Day 1], Week 22)
- Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs): Cohort A(From first dose of study treatment (Day 1) maximum up to 10 weeks post Week 22 (maximum up to approximately 32 weeks))
- Number of Participants With Any Abnormalities in Laboratory Test Parameters: Cohort A(From first dose of study treatment (Day 1) up to Week 22)
- Number of Participants With Abnormalities in Vital Signs: Cohort A(From first dose of study treatment (Day 1) maximum up to 10 weeks post Week 22 (maximum up to approximately 32 weeks))
- Number of Participants With TEAEs and TEASAEs: Cohort B(From first dose of study treatment (Day 1) maximum up to 10 weeks post Week 12 (maximum up to approximately 22 weeks))
- Number of Participants With Any Abnormalities in Laboratory Test Parameters: Cohort B(From first dose of study treatment (Day 1) maximum up to 4 weeks post Week 12 (maximum up to approximately 16 weeks))
- Number of Participants With Abnormalities in Vital Signs: Cohort B(From start of study drug on Day 1 maximum up to 4weeks post last dose on Week 12 (maximum up to approximately Week 16))