A Study of Enlicitide Decanoate (MK-0616, an Oral PCSK9 Inhibitor) in Children and Adolescents With Heterozygous Familial Hypercholesterolemia (MK-0616-029)
- Conditions
- Heterozygous Familial Hypercholesterolemia (HeFH)
- Interventions
- Drug: Placebo
- Registration Number
- NCT07058077
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 153
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); or a nonstatin LLT with documented intolerance to at least 2 different statins or 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
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 principal 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part A: Enlicitide Decanoate Enlicitide Decanoate Participants receive enlicitide decanoate orally once daily (QD) at a dosage determined by age for up to 2 weeks. Part B: Placebo Placebo Participants receive placebo orally QD for up to 24 weeks. Open-Label Extension: Enlicitide Decanoate 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. Part B: Enlicitide Decanoate Enlicitide Decanoate Participants receive enlicitide decanoate QD at a dosage determined by age for up to 24 weeks.
- Primary Outcome Measures
Name Time Method Part A: Maximum Plasma Concentration (Cmax) of Enlicitide 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 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) 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) 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 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.
- Secondary Outcome Measures
Name Time Method Part B: Percent Change from Baseline in Apolipoprotein B (ApoB) Baseline and week 24 Blood samples will be collected to determine the percent change from baseline in apolipoprotein B.
Part B: Percent Change from Baseline in Non-High-Density Lipoprotein Cholesterol (non-HDL-C) Baseline and week 24 Blood samples will be collected to determine the percent change from baseline in non-HDL-C.
Part B: Percent Change from Baseline in Lipoprotein (a) (Lp(a)) Baseline and week 24 Blood samples will be collected to determine the percent change from baseline in Lp(a).
Part B: Percentage of Participants With LDL-C <130 mg/dL at Week 24 Week 24 The percentage of participants with LDL-C \<130 mg/dL at week 24 will be reported.
Part B: Percentage of Participants With ≥50% LDL-C LDL-C Reduction from Baseline at Week 24 Baseline and week 24 The percentage of participants with ≥50% LDL-C reduction from baseline at week 24 will be reported.
Part B: Percentage of Participants With LDL-C <100 mg/dL at Week 24 Week 24 The percentage of participants with LDL-C \<100 mg/dL at week 24 will be reported.
Change in Carotid Intima-media Thickness (cIMT) Baseline and week 24 Ultrasound measurements will be performed to determine the change from baseline in cIMT.