Efficacy and Safety of Lomitapide in Paediatric Patients With Homozygous Familial Hypercholesterolaemia (HoFH)

Phase 3

Completed

Conditions: Homozygous Familial Hypercholesterolaemia (HoFH)

Interventions: Drug: Lomitapide

Registration Number: NCT04681170

Lead Sponsor: Amryt Pharma

Brief Summary: This is a single arm, open label, multi centre phase III study to evaluate the efficacy and long term safety of lomitapide in paediatric patients with HoFH receiving stable lipid lowering therapy (LLT) (including lipoprotein apheresis (LA), when applicable) comprising of the following phases:

* Screening Period (starting at Week 12, i.e. ≤12 weeks prior to Baseline for up to 6 weeks)

* Stratified Enrolment and Start of Run in Period (starting at minimum at Week 6, i.e., 6 weeks prior to Baseline for a minimum of 6 weeks):

* Efficacy Phase (starting at Baseline, i.e. Day \[D\] 0 for 24 weeks±3 days

* Safety Phase (starting at Week 24±3 days for 80±1 weeks)

Detailed Description: Lomitapide has been approved for use in adult patients with HoFH in the European Union (EU) and European Economic Area (EEA), United States of America (USA), Israel, Argentina, Canada, Colombia, and Japan. This study is designed to determine if lomitapide is effective and can be safely administered to paediatric patients with HoFH. If the efficacy and safety so far observed in adults is confirmed in paediatric patients, the potential exists to significantly lower low-density lipoprotein cholesterol (LDL-C) levels in paediatric patients with HoFH. Furthermore, the lower LDL-C levels may reduce atherosclerosis progression and would be expected to benefit these paediatric patients with HoFH.

A single arm, non comparator design has been selected due to the rarity of the disease and because the evaluation of safety variables such as growth and sexual maturation requires longer term observation than would be feasible in the context of a placebo controlled study.

To mitigate the disadvantages of a single arm design, the study includes a Run in Period of at least 6 weeks during which current lipid lowering therapy (LLT) (including lipoprotein apheresis (LA), when applicable) will be stabilised to establish baseline levels allowing each patient to serve as his/her own control. Patients will also remain on stable LLT (including LA, when applicable) during the Efficacy Phase of the study through Week 24±3 days.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 46

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Age 5-10 years	Lomitapide	Lomitapide dosing commenced with 2mg at week 1 for 8 Weeks,then increased to 5mg at Week 8±3 days, 10 mg at Week 12±3 days to the maximum allowable dose of 20 mg by Week 16±3 days or the MTD by Week 20±3 days based upon acceptable safety and tolerability criteria in addition to LDL C values.
Age 11-15 years	Lomitapide	Lomitapide dosing commenced with 2mg at week 1 for 4 Weeks, then increased to 5mg at Week 4±3 days, 10 mg at Week 8±3 days, 20mg at Week 12±3 days to the maximum allowable dose of 40mg by Week 16±3 days or the MTD by Week 20±3 days based upon acceptable safety and tolerability criteria in addition to LDL C values.
Age 16 to ≤17 years	Lomitapide	Lomitapide dosing commenced with 5mg at week 1 for 4 Weeks, then increased to 10mg at Week 4±3 days, 20 mg at Week 8±3 days, 40mg at Week 12±3 days to the maximum allowable dose of 60mg by Week 16±3 days or the MTD by Week 20±3 days based upon acceptable safety and tolerability criteria in addition to LDL C values.

Primary Outcome Measures

Name	Time	Method
Efficacy Endpoint: Percent Change in Low-density Lipoprotein Cholesterol (LDL C) at Week 24 Compared to Baseline	Baseline through Week 24	To evaluate the efficacy of lomitapide, as defined by the percent change in low density lipoprotein cholesterol (LDL C) at the maximum tolerated dose (MTD)

Secondary Outcome Measures

Name	Time	Method
Efficacy Endpoint: Percent Change From Baseline at Week 24 for Various Lipid Parameters	Baseline through Week 24	To evaluate the efficacy of lomitapide, as defined by the percent change of the following lipid parameters at the maximum tolerated dose (MTD): * Non-high-density lipoprotein cholesterol (Non-HDL-C) * Total cholesterol (TC) * Very-low-density lipoprotein cholesterol (VLDL-C) * Apolipoprotein B (Apo B) * TG (Triglycerides)
Efficacy Endpoint: Percent Change From Baseline at Week 24 for Lp(a)	Baseline through Week 24	To evaluate the efficacy of lomitapide, as defined by the percent change in Lp(a) at the maximum tolerated dose (MTD)
Percent Change From Baseline at All Other Time Points Through Week 104 for LDL-C	Baseline through Week 104	To evaluate the efficacy of lomitapide, as defined by the percent change in LDL-C at the maximum tolerated dose (MTD)
Percent Change From Baseline at All Other Time Points Through Week 104 for Non-HDL-C	Baseline through Week 104	To evaluate the efficacy of lomitapide, as defined by the percent change in Non-HDL-C at the maximum tolerated dose (MTD)
Percent Change From Baseline at All Other Time Points Through Week 104 for TC	Baseline through Week 104	To evaluate the efficacy of lomitapide, as defined by the percent change in TC at the maximum tolerated dose (MTD)
Percent Change From Baseline at All Other Time Points Through Week 104 for VLDL-C	Baseline through Week 104	To evaluate the efficacy of lomitapide, as defined by the percent change in VLDL-C at the maximum tolerated dose (MTD)
Percent Change From Baseline at All Other Time Points Through Week 104 for Apo B	Baseline through Week 104	To evaluate the efficacy of lomitapide, as defined by the percent change in apo B at the maximum tolerated dose (MTD)
Percent Change From Baseline at All Other Time Points Through Week 104 for TG	Baseline through Week 104	To evaluate the efficacy of lomitapide, as defined by the percent change in TG at the maximum tolerated dose (MTD)
Percent Change From Baseline at All Other Time Points Through Week 104 for Lipoprotein(a) (Lp(a))	Baseline through Week 104	To evaluate the efficacy of lomitapide, as defined by the percent change in Lp(a) at the maximum tolerated dose (MTD)
Percent Change in TC/HDL-C Ratio From Baseline at All Other Time Points to Week 104	Baseline through Week 104	To evaluate the efficacy of lomitapide, as defined by the percent change in TC/HDL-C ratio at the maximum tolerated dose (MTD)
Percent Change in HDL-C From Baseline at All Other Time Points to Week 104	Baseline through Week 104 week	To evaluate the efficacy of lomitapide, as defined by the percent change in HDL-C at the maximum tolerated dose (MTD)
Change in LLT From Week 28 Through Week 104	Week 28 through Week 104	To evaluate the efficacy of lomitapide, as defined by the change in background lipid lowering therapy
Change in LA From Week 28 Through Week 104	Week 28 through Week 104	To evaluate the efficacy of lomitapide, as defined by the change in lipoprotein apheresis
Number and Percentage of Patients Achieving European Atherosclerosis Society (EAS) Recommended Target (2013) of LDL-C at Any Timepoint Between Baseline and Week 24	Baseline through Week 24	To evaluate the efficacy of lomitapide, as defined by the number and percentage of patients achieving EAS recommended target (2013) of LDL-C
Number and Percentage of Patients Achieving EAS Recommended Target (2013) of LDL-C at Any Time in the Study	Baseline through Week 104	To evaluate the efficacy of lomitapide, as defined by the number and percentage of patients achieving EAS recommended target (2013) of LDL-C

Trial Locations

Locations (12): Universtiats-Kinderlinik Heidelberg
🇩🇪
Heidelberg, Baden-Wurttemberg, Germany
University Hospital of Cologne
🇩🇪
Cologne, Germany
University Medical Center Hamburg-Eppendorf
🇩🇪
Hamburg, Germany
Chaim Sheba Medical Center
🇮🇱
Ramat Gan, Israel
U.O.C. Clinica Medica 1
🇮🇹
Padua, Padua, Italy
Bambino Gesù Children's Hospital,
🇮🇹
Roma, Italy
King Abdullah International Medical Research Centre (KAIMRC),
🇸🇦
Riyadh, Saudi Arabia
King Faisal Specialist Hospital
🇸🇦
Riyadh, Saudi Arabia
Hospital Universitari Sant Joan
🇪🇸
Reus, Tarragona,, Spain
Hospital Abente y Lago
🇪🇸
A Coruña, Spain
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Universtiats-Kinderlinik Heidelberg
🇩🇪Heidelberg, Baden-Wurttemberg, Germany