Clinical trial NCT02765841: Evaluate the Efficacy and Safety of Lomitapide in Pediatric Patients With Homozygous Familial Hypercholesterolemia on Stable Lipid-lowering Therapy
Official title: 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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE3
Conditions: Homozygous Familial Hypercholesterolemia
Keywords: HoFH
Lead sponsor: Aegerion Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2016-05-09
Enrollment: 0
Sex: ALL
Minimum age (years): 5
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

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