Efficacy and Safety of Lomitapide in Paediatric Patients With Homozygous Familial Hypercholesterolaemia (HoFH)
- Conditions
- Homozygous Familial Hypercholesterolaemia (HoFH)
- Interventions
- 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 LLT (including 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 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 LLT (including 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
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 16 to ≤17 years Lomitapide Lomitapide dosing will commence with 5mg at week 1 for 4 Weeks, then increase to 10mg Week 4±3 days,20 mg at Week 8±3 days,40mgs at week, 12±3 days to the maximum allowable dose of 60 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 5-10 years Lomitapide Age 5-10 years Lomitapide dosing will commence with 2mg at week 1 for 8 Weeks,then increase to 5mg 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 Age11-15years Lomitapide Lomitapide dosing will commence with 2mg at week 1 for 4 Weeks, then increase to 5mg Week 4±3 days, 10 mg at Week 8±3 days,20mgs at week, 12±3 days to the maximum allowable dose of 40 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
- Primary Outcome Measures
Name Time Method Safety endpoints AE reporting Baseline through Week 104±1 week Incidence, severity, and relatedness of AEs
Efficacy endpoint Percent change in LDL C Baseline through Week 104±1 week 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 Percent change from Baseline at Week 24±3 days for the following lipid parameters: TC, Non HDL C, VLDL C, TG, Lp(a), and apoB Baseline through Week 104±1 week Percent change from Baseline at all other time points through Week 104±1 week for the following lipid parameters: LDL C, TC, Non HDL C, VLDL C, TG, Lp(a), and apo B Baseline through Week 104±1 week • Change in LLT and LA from Week 24±3 days through Week 104±1 week Baseline through Week 104±1 week • Total number and percent of patients achieving the EAS recommended target LDL C of <135 mg/dL (3.5 mmol/L) in paediatric HoFH patients at Week 24±3 days and at any time on study Baseline through Week 104±1 week
Trial Locations
- Locations (12)
University Hospital of Cologne
🇩🇪Cologne, Germany
U.O.C. Clinica Medica 1
🇮🇹Padova, Padua, Italy
E.P.S. Fattouma Bourguiba Hospital
🇹🇳Monastir,, Tunisia
Bambino Gesù Children's Hospital,
🇮🇹Roma, Italy
Hospital Abente y Lago
🇪🇸A Coruña, Spain
University Medical Center Hamburg-Eppendorf
🇩🇪Hamburg, Germany
Universtiats-Kinderlinik Heidelberg
🇩🇪Heidelberg, Baden-Wurttemberg, Germany
Chaim Sheba Medical Center
🇮🇱Ramat Gan,, Israel
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 Clinico Universitario of Valencia
🇪🇸Valencia, Spain