An Operationally Seamless Phase 2/3 Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of Enlicitide Decanoate in Pediatric Participants With Heterozygous Familial Hypercholesterolemia
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 153
- 试验地点
- 48
- 主要终点
- Part A: Maximum Plasma Concentration (Cmax) of Enlicitide
研究概览
简要总结
This study is designed to learn if enlicitide decanoate is safe and effective to treat children and adolescents with heterozygous familial hypercholesterolemia (HeFH) and high amounts of low-density lipoprotein cholesterol (LDL-C) in the blood.
The goals of this study are to learn about the safety of enlicitide and if children tolerate it, what happens to enlicitide in a child's body over time, and if enlicitide works to lower cholesterol levels in children more than a placebo.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Part A and the extension period are open-label. Part B is double-blinded.
入排标准
- 年龄范围
- 6 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Inclusion criteria include, but are not limited to:
- •Has possible or definite diagnosis of HeFH based on a locally accepted diagnostic algorithm or diagnosis by genetic testing results
- •Has a fasted LDL-C value (evaluated by the central laboratory) that is ≥130 mg/dL
- •Is receiving either:
- •An optimized daily dose of statin (± nonstatin LLT)
- •A nonstatin LLT with documented intolerance to at least 2 different statins, or documented intolerance to 1 statin plus refusal of statin therapy by the participant or legally acceptable representative
- •Is on a stable dose of all background LLTs for at least 30 days prior to screening, with no medication or dose changes planned during participation in Part A or Part B
排除标准
- •Exclusion criteria include, but are not limited to:
- •Has a history of homozygous FH based on genetic or clinical criteria, or history of known compound heterozygous FH, or double heterozygous FH
- •Has a history of nephrotic syndrome
- •Has any clinically significant malabsorption condition based on investigator assessment
- •Was previously treated/is being treated with certain other cholesterol lowering medications, including proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors without adequate washout
研究组 & 干预措施
Part B: Placebo
Participants receive placebo orally QD for up to 24 weeks.
干预措施: Placebo (Drug)
Open-Label Extension: Enlicitide Decanoate
Participants who complete either Part A or Part B may enroll in this open-label extension arm. Participants in the extension arm receive enlicitide decanoate QD at a dosage determined by age for up to 3 years.
干预措施: Enlicitide Decanoate (Drug)
Part B: Enlicitide Decanoate
Participants receive enlicitide decanoate QD at a dosage determined by age for up to 24 weeks.
干预措施: Enlicitide Decanoate (Drug)
Part A: Enlicitide Decanoate
Participants receive enlicitide decanoate orally once daily (QD) at a dosage determined by age for up to 2 weeks.
干预措施: Enlicitide Decanoate (Drug)
结局指标
主要结局
Part A: Maximum Plasma Concentration (Cmax) of Enlicitide
时间窗: At designated timepoints (up to 24 hours postdose on day 14)
Blood samples will be collected to determine the Cmax of enlicitide.
Part A: Area Under the Concentration-Time Curve from 0 to 24 Hours (AUC0-24) of Enlicitide
时间窗: At designated timepoints (up to 24 hours postdose on day 14)
Blood samples will be collected to determine the AUC0-24 of enlicitide.
Part B: Percent Change from Baseline in Low-Density Lipoprotein Cholesterol (LDL-C)
时间窗: Baseline and Week 24
Blood samples will be collected to determine the percent change from baseline in LDL-C.
Number of Participants Who Experience an Adverse Event (AE)
时间窗: Up to approximately 188 weeks
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
Number of Participants Who Discontinue Study Treatment Due to an AE
时间窗: Up to approximately 180 weeks
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
Part A: Maximum Plasma Concentration (Cmax) of Enlicitide
时间窗: At designated timepoints (up to 24 hours postdose on day 14)
Blood samples will be collected to determine the Cmax of enlicitide.
Number of Participants Who Discontinue Study Treatment Due to an AE
时间窗: Up to approximately 180 weeks
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
次要结局
- Part B: Percent Change from Baseline in Apolipoprotein B (ApoB)(Baseline and week 24)
- Part B: Percent Change from Baseline in Non-High-Density Lipoprotein Cholesterol (non-HDL-C)(Baseline and week 24)
- Part B: Percent Change from Baseline in Lipoprotein (a) (Lp(a))(Baseline and week 24)
- Part B: Percentage of Participants With LDL-C <130 mg/dL at Week 24(Week 24)
- Part B: Percentage of Participants With ≥50% LDL-C LDL-C Reduction from Baseline at Week 24(Baseline and week 24)
- Part B: Percentage of Participants With LDL-C <100 mg/dL at Week 24(Week 24)
- Change in Carotid Intima-media Thickness (cIMT)(Baseline and week 24)
- Part B: Percent Change from Baseline in Apolipoprotein B (ApoB)(Baseline and week 24)
- Part B: Percent Change from Baseline in Non-High-Density Lipoprotein Cholesterol (non-HDL-C)(Baseline and week 24)
- Part B: Percent Change from Baseline in Lipoprotein (a) (Lp(a))(Baseline and week 24)
- Part B: Percentage of Participants With ≥50% LDL-C LDL-C Reduction from Baseline at Week 24(Baseline and week 24)
- Part B: Percentage of Participants With LDL-C <100 mg/dL at Week 24(Week 24)
- Change in Carotid Intima-media Thickness (cIMT)(Baseline and week 24)