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

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Homozygous Familial Hypercholesterolemia
• Intervention / Treatment: Drug: Lomitapide

• Study Type: Interventional
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female aged ≥5 and <18 years with diagnosed functional HoFH
2. 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
3. Negative pregnancy test at Screening and during the study for females of child bearing age
4. 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:

1. Other forms of primary hyperlipoproteinemia and secondary causes of hypercholesterolemia (e.g., nephrotic syndrome, hypothyroidism).
2. Abnormal liver function test at Screening
3. Moderate or severe hepatic impairment or active liver disease
4. Serum creatine phosphokinase (CPK) level >2 × ULN.
5. Chronic renal insufficiency
6. History of drug abuse within the last 3 years or habitual alcohol consumption
7. New York Heart Association (NYHA) Class III or IV congestive heart failure.
8. Uncontrolled hypertension
9. In the judgment of the PI, precocious or delayed puberty or endocrine disorder that would affect growth
10. History of non-skin malignancy or other cancers occurring within the past 3 years
11. History of inflammatory bowel disease or other malabsorption syndrome or a history of bowel resection, gastric bypass, or other weight loss surgical procedure.
12. Use of mipomersen within 6 months of Screening.
13. Any medical condition for which the life expectancy is predicted to be less than 5 years.
14. 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.
15. Participation in an interventional clinical study within 6 weeks for a statin therapy or within 6 months for any other unapproved therapy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lomitapide	Drug: Lomitapide; Other Names: Juxtapid, Lojuxta

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Aegerion Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start: May 1, 2016
• Primary Completion (Anticipated): March 1, 2017
• Study Completion (Anticipated): December 1, 2019

Study Registration Dates

• First Submitted: April 27, 2016
• First Submitted That Met QC Criteria: May 6, 2016
• First Posted (Estimate): May 9, 2016

Study Record Updates

• Last Update Posted (Actual): February 22, 2018
• Last Update Submitted That Met QC Criteria: February 21, 2018
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Keywords: HoFH
• Additional Relevant MeSH Terms: Metabolic Diseases; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Lipid Metabolism, Inborn Errors; Hyperlipoproteinemias; Hypercholesterolemia; Hyperlipoproteinemia Type II
• Other Study ID Numbers: AEGR-733-020