Efficacy and Safety of Lomitapide in Paediatric Patients With Homozygous Familial Hypercholesterolaemia (HoFH)

Inclusion criteria

Male and female patients aged 5 to ≤17 years with HoFH as defined by any of the following criteria recommended by the Consensus Panel on Familial Hypercholesterolaemia of the EAS (Cuchel, Bruckert et al. 2014):

1. Genetic confirmation of 2 mutant alleles at the LDL receptor (LDLR), apo B, Proprotein convertase subtilisin/kexin type 9 (PCSK9), or LDL receptor adapter protein 1 (LDLRAP1) gene locus OR
2. An untreated LDL C >500 mg/dL (13 mmol/L) or treated LDL C ≥300 mg/dL (8 mmol/L ) together with either Cutaneous or tendon xanthoma before age 10 years or Untreated LDL C levels consistent with heterozygous FH in both parents

Baseline LDL C on LLT (maximum concentration [Cmax] immediately prior to LA, if applicable)

1. >160 mg/dL (4.1 mmol/L, no documented cardiovascular disease [CVD]) or
2. >130 mg/dL (3.4 mmol/L, established CVD defined as aortic valve disease and/or coronary atherosclerosis)
3. Body weight ≥15 kg or BMI and height both >10th percentile according to World Health Organization (WHO) Growth Charts for Boys and Girls 5 to 19 Years of Age
4. Patient and/or his/her legal representative has/have been informed, has/have read and understood the patient information/informed consent form, and has/have given written informed assent/consent

Patient and/or his/her legal representative must be able and willing to follow study procedures and instructions, particularly that

1. LLT (including LA, when applicable) must be stable for at least 6 weeks prior to Baseline (Run in Period) and remain stable through Week 24±3 days (end of Efficacy Phase)
2. The patient must be compliant with both the low fat diet supplying <20% of energy (calories) from fat or <30 g fat, whichever is the lesser amount starting at the beginning of the Run in Period and the dietary supplement regimen starting at Week 2 of the Run in Period, both continuing until completion of the study
3. Postmenarchal female adolescents must be willing to use an effective form of birth control with failure rates <1% per year (e.g., implant, injectable, combined oral contraceptive, intrauterine contraceptive device, sexual abstinence, vasectomy or vasectomised partner) during participation in the study (and at least 4 weeks thereafter). Patients taking oestrogen based oral contraceptives should be advised about possible loss of effectiveness due to diarrhea and/or vomiting. Additional contraceptive measures should be used for 7 days after resolution of symptoms.
4. Patient must be in stable physical and mental health at screening

Exclusion criteria

1. Other forms of primary hyperlipoproteinaemia and secondary causes of hypercholesterolaemia (e.g., nephrotic syndrome, hypothyroidism)
2. Contraindications for the use of lomitapide according to section 4.3 of the European Medicines Agency (EMA) Summary of Product Characteristics (SmPC), such as hypersensitivity to the active substance or to any of the excipients listed in Section 6.1 of the SmPC, known significant or chronic inflammatory bowel disease or malabsorption
3. Moderate (Child Pugh B) or severe hepatic impairment (Child Pugh C), active liver disease and/or abnormal liver function tests at screening (AST or ALT >1.5 x upper limit of normal (ULN) and/or total bilirubin >1.5 x ULN in the absence of Gilbert's syndrome or AP >1.5 x ULN [based on appropriate age and gender normal values])
4. Serum CK >2 x ULN
5. Chronic renal insufficiency with glomerular filtration rate (GFR) <70 mL/min/1.73 m2 calculated using the Schwartz formula
6. Uncontrolled hypertension (defined as mean systolic and/or diastolic blood pressure ≥95% of normal for age and sex) despite medical therapy
7. New York Heart Association (NYHA) Class III or IV congestive heart failure
8. Precocious/delayed puberty or endocrine disorder affecting growth (e.g., hypothyroidism, premature adrenarche)
9. History of drug abuse within the last 3 years or habitual alcohol consumption (defined as >1 ounce [28 g] of liquor or 4 ounce glass [113 g] of wine, or the equivalent, ≥3 times per week)
10. Life expectancy predicted to be <5 years
11. History of a non skin malignancy (with the exception of cervical cancer in situ) within 3 years prior to enrolment
12. Treatment with any Investigational Medicinal Product (IMP) within 6 months or 5 times the terminal half life of the corresponding IMP, whichever is longer, before the screening visit
13. Patient is a dependent of the sponsor, of the investigational team or his/her immediate family
14. Pregnant or nursing women