Evaluate the Efficacy and Safety of Lomitapide in Pediatric Patients With Homozygous Familial Hypercholesterolemia on Stable Lipid-lowering Therapy

Study Overview
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Brief Summary
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This is a Phase 3 single-arm, open-label, international, multi-center clinical trial to evaluate the efficacy and safety of lomitapide in pediatric patients with HoFH who are receiving stable lipid-lowering therapy, including LDL apheresis. The study is comprised of a 12-week Run-in Period, a primary 24-week Efficacy Phase, followed by an 80-week Safety Phase.

Official Title
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A Phase 3, Single-arm, Open-label, International, Multi-center Study to Evaluate the Efficacy and Safety of Lomitapide in Pediatric Patients With Homozygous Familial Hypercholesterolemia on Stable Lipid-lowering Therapy

Conditions
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Homozygous Familial Hypercholesterolemia

Intervention / Treatment
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* Drug: Lomitapide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female aged ≥5 and <18 years with diagnosed functional HoFH Patient must weigh at least 15 kg and be at or above the 10th percentile in BMI and at least 10th percentile in height for age and gender based on CDC growth charts Negative pregnancy test at Screening and during the study for females of child bearing age Potentially sexually active female patients who are of child-bearing age must either be sexually abstinent or follow two acceptable methods of contraception Exclusion Criteria: Other forms of primary hyperlipoproteinemia and secondary causes of hypercholesterolemia (e.g., nephrotic syndrome, hypothyroidism). Abnormal liver function test at Screening Moderate or severe hepatic impairment or active liver disease Serum creatine phosphokinase (CPK) level >2 × ULN. Chronic renal insufficiency History of drug abuse within the last 3 years or habitual alcohol consumption New York Heart Association (NYHA) Class III or IV congestive heart failure. Uncontrolled hypertension In the judgment of the PI, precocious or delayed puberty or endocrine disorder that would affect growth History of non-skin malignancy or other cancers occurring within the past 3 years History of inflammatory bowel disease or other malabsorption syndrome or a history of bowel resection, gastric bypass, or other weight loss surgical procedure. Use of mipomersen within 6 months of Screening. Any medical condition for which the life expectancy is predicted to be less than 5 years. Any patient who is unable to avoid treatment with strong or moderate cytochrome P450 3A4 (CYP3A4) inhibitors, or other drugs contraindicated for use with lomitapide during the study. Participation in an interventional clinical study within 6 weeks for a statin therapy or within 6 months for any other unapproved therapy.

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lomitapide<br> | Drug: Lomitapide<br> <br> * Other names: Juxtapid, Lojuxta;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent change in LDL-C |  | Baseline, Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change in TC |  | Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 68, 80, 92, 104 | 
| Percent change in non-HDL-C |  | Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 68, 80, 92, 104 | 
| Percent change in HDL-C |  | Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 68, 80, 92, 104 | 
| Percent change in TG |  | Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 68, 80, 92, 104 | 
| Percent change in VLDL-C |  | Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 68, 80, 92, 104 | 
| Percent change in Lp(a) |  | Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 68, 80, 92, 104 | 
| Percent change in apo B |  | Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 68, 80, 92, 104 | 
| Percent change in apo A-1 |  | Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 68, 80, 92, 104 | 
| Percent change in LDL-C |  | Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 68, 80, 92, 104 | 
| Changes in lipid-lowering therapy |  | Week 24 through Week 104 | 
| Changes in LDL apheresis |  | Week 24 through Week 104 | 
| Percent of patients achieving goal (LDL-C of <100 mg/dL [2.6 mmol/L] for patients without documented cardiovascular disease [CVD] at Baseline |  | Week 24 and through Week 108 | 
| Percent of patients achieving goal LDL-C of <70 mg/dL [1.8 mmol/L]) for patients with documented CVD at Baseline. |  | Week 24 and through Week 108 | 
| Changes in laboratory parameters (including hepatic and renal function) |  | Baseline through Year 2 | 
| Reported Adverse Events |  | Baseline through Year 2 | 
| Electrocardiogram (ECG) changes |  | Baseline through Year 2 | 
| Pulmonary function tests (PFTs) |  | Baseline through Year 2 | 
| Bone health/age (x-ray of the wrist) |  | Baseline through Year 2 | 
| Height Measurement |  | Baseline through Year 2 | 
| Weight Measurement |  | Baseline through Year 2 | 
| Body Mass Measurement |  | Baseline through Year 2 | 
| Tanner Staging |  | Baseline through Year 2 | 
| Percent change in hepatic fat |  | Baseline through Year 2 | 
| Blood Pressure |  | Baseline through Year 2 | 
| Heart Rate |  | Baseline through Year 2 | 
| Temperature |  | Baseline through Year 2 | 
| Respiration (breaths/min) |  | Baseline through Year 2 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HoFH