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

Phase 3
Withdrawn
Conditions
Homozygous Familial Hypercholesterolemia
Interventions
Registration Number
NCT02765841
Lead Sponsor
Aegerion Pharmaceuticals, Inc.
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
WITHDRAWN
Sex
All
Target Recruitment
Not specified
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 & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
LomitapideLomitapide-
Primary Outcome Measures
NameTimeMethod
Percent change in LDL-CBaseline, Week 24
Secondary Outcome Measures
NameTimeMethod
Electrocardiogram (ECG) changesBaseline through Year 2
Pulmonary function tests (PFTs)Baseline through Year 2
Percent change in non-HDL-CBaseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 68, 80, 92, 104
Percent Change in TCBaseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 68, 80, 92, 104
Percent change in TGBaseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 68, 80, 92, 104
Percent change in HDL-CBaseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 68, 80, 92, 104
Changes in lipid-lowering therapyWeek 24 through Week 104
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
Percent change in VLDL-CBaseline, 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 LDL-CBaseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 68, 80, 92, 104
Percent change in apo BBaseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 68, 80, 92, 104
Percent change in apo A-1Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 68, 80, 92, 104
Changes in LDL apheresisWeek 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 BaselineWeek 24 and through Week 108
Reported Adverse EventsBaseline through Year 2
Height MeasurementBaseline through Year 2
Weight MeasurementBaseline through Year 2
Body Mass MeasurementBaseline through Year 2
Tanner StagingBaseline through Year 2
Percent change in hepatic fatBaseline through Year 2
Blood PressureBaseline through Year 2
Heart RateBaseline through Year 2
TemperatureBaseline through Year 2
Respiration (breaths/min)Baseline through Year 2
Bone health/age (x-ray of the wrist)Baseline through Year 2
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