Homozygous familial hypercholesterolemia (HoFH). MedDRA version: 18.1 Level: LLT Classification code 10057080 Term: Homozygous familial hypercholesterolemia System Organ Class: 100000004850
Conditions
Sponsors
Aegerion Pharmaceuticals Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female aged =5 and500 mg/dL (13.0 mmol/L) AND TG 250 mg/dL (6.5 mmol/L), d) Average fasting LDL-C >300 mg/dL (7.8 mmol/L) on maximally tolerated lipid-lowering therapy as decided by the treating physician with both parents having documented untreated TC >250 mg/dL (6.5 mmol/L). 2. Baseline LDL-C >160 mg/dL (4.1 mmol/L) on background therapy and no documented CVD or baseline LDL-C >130 mg/dL (3.4 mmol/L) on background therapy for patients with established CVD (defined as aortic valve disease and/or coronary atherosclerosis). 3. Parent/guardian is able to provide written informed consent for patient (according to local legal requirements) prior to any trial procedures. 4. Patient must provide informed assent or informed consent according to local legal requirements and must understand the trial procedures and that he or she can withdraw from the study at any time. 5. 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 the CDC growth charts. 6. Patient and parent/guardian understand and agree that lipid-lowering therapy, including LDL apheresis, must be stable for at least 12 weeks prior to Day 1 of treatment and remain stable through the Week 24 visit of the study. 7. Patient must be in stable physical and mental health at Screening. 8. Patient/guardian must agree to be compliant with a low-fat diet supplying =65 years)
Exclusion criteria
Exclusion criteria: 1. Other forms of primary hyperlipoproteinemia and secondary causes of hypercholesterolemia (e.g., nephrotic syndrome, hypothyroidism). 2. Abnormal liver function test (LFT) at Screening (aspartate aminotransferase [AST] or alanine aminotransferase [ALT] >1.5 times the upper limit of normal [× ULN] and/or total bilirubin >1.5 × ULN in the absence of Gilbert’s syndrome, or alkaline phosphatase [ALP] >1.5 × ULN based on appropriate age and gender normal values). 3. Moderate or severe hepatic impairment or active liver disease. 4. Serum creatine phosphokinase (CPK) level >2 × ULN. 5. Chronic renal insufficiency with glomerular filtration rate (GFR) 1 ounce [28 grams] of liquor or 4 ounce glass [113 grams] of wine, or the equivalent, 3 or more times per week). 7. New York Heart Association (NYHA) Class III or IV congestive heart failure. 8. Uncontrolled hypertension (defined as mean systolic or diastolic blood pressure >95% of the ULN for age and sex) despite medical therapy. 9. In the judgment of the PI, precocious or delayed puberty or endocrine disorder that would affect growth (e.g., hypothyroidism, premature adrenarche). 10. History of non-skin malignancy (with the exception of treated basal cell or squamous cell cancer or noninvasive cervical cancer in situ) 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of lomitapide as defined by the mean percent change in LDL-C (low density lipoprotein cholesterol) at the maximum tolerated dose at Week 24 compared to baseline when added to stable lipid-lowering therapy (including LDL apheresis when applicable) in pediatric and adolescent patients (=5 to <18 years of age) with HoFH.;Secondary Objective: The secondary objectives are to evaluate the efficacy, safety, and pharmacokinetics of lomitapide in pediatric patients with HoFH. ;Primary end point(s): The mean percent change in LDL-C from Baseline at Week 24.;Timepoint(s) of evaluation of this end point: From Baseline at Week 24. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary Efficacy Endpoints: The mean percent change from Baseline at Week 24 for the following lipid parameters: - TC - Non-HDL-C - HDL-C - TG - VLDL-C - Lp(a) - Apo B - Apo A-1 The mean percent change from Baseline at all other time points through Week 104 for the following lipid parameters : - LDL-C - TC - Non-HDL-C - HDL-C - TG - VLDL-C - Lp(a) - Apo B - Apo A-1 Changes in lipid-lowering therapy and LDL apheresis from Week 24 through Week 104. Number (percent) of patients achieving goal at Week 24 and at any time on study (LDL-C of <100 mg/dL [2.6 mmol/L] for patients without documented CVD at Baseline; LDL-C of <70 mg/dL [1.8 mmol/L] for patients with documented CVD at Baseline). Safety evaluations and endpoints to be evaluated in this study through Year 2/End of Treatment include: 1. AEs 2. Physical examinations including growth and sexual maturation assessments and a genitourinary examination per the PI’s judgment 3. Weight, height, and BMI 4. Vital signs 5. Bone health a. X-rays of the wrist to assess bone health and bone age b. Assessed indirectly using growth to track age-appropriate progress, and measurement of 25-hydroxyvitamin D and total and uncarboxylated osteocalcin levels (as a reflection of vitamin K levels) 6. 12-Lead safety ECG (read locally) 7. PFTs 8. Tanner staging 9. Hepatic fat content (percent) as measured by MRI; if MRI is contraindicated, another method of imaging will be performed (e.g., CT or ultrasound scan) 10. Laboratory tests including the following: a. Liver function tests including: ALT, AST, ALP, total bilirubin, gamma-glutamyl transferase (GGT), and serum albumin b. Creatinine phosphokinase (CPK) c. Serum levels of fat-soluble vitamins d. Serum levels of EFAs e. Sex hormones (serum testosterone, serum estradiol) for patients assessed at Tanner Stage 2 or higher f. Pituitary-adrenal hormones (TSH, FSH, LH, ACTH, and AM cortisol) for patients assessed at Tanner S | — |
Countries
Austria, Canada, Germany, Greece, Israel, Italy, Turkey
Contacts
Public ContactPediatric trial information
Aegerion Pharmaceuticals Inc.
Outcome results
None listed