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

NCT04681170 | Completed Phase 3 Results DMC

• 1 other identifier: APH-19
• Study Type: interventional
• Target: 46
• Locations: 6 countries
• Sites: 12

Brief Summary

This is a single arm, open label, multi centre phase III study to evaluate the efficacy and long term safety of lomitapide in paediatric patients with HoFH receiving stable lipid lowering therapy (LLT) (including lipoprotein apheresis (LA), when applicable) comprising of the following phases:

• Screening Period (starting at Week 12, i.e. ≤12 weeks prior to Baseline for up to 6 weeks)
• Stratified Enrolment and Start of Run in Period (starting at minimum at Week 6, i.e., 6 weeks prior to Baseline for a minimum of 6 weeks):
• Efficacy Phase (starting at Baseline, i.e. Day \[D\] 0 for 24 weeks±3 days
• Safety Phase (starting at Week 24±3 days for 80±1 weeks)

Conditions

Homozygous Familial Hypercholesterolaemia (HoFH)

Outcome Measures

Primary Outcomes (1)

• Efficacy Endpoint: Percent Change in Low-density Lipoprotein Cholesterol (LDL C) at Week 24 Compared to Baseline

  To evaluate the efficacy of lomitapide, as defined by the percent change in low density lipoprotein cholesterol (LDL C) at the maximum tolerated dose (MTD)

  Baseline through Week 24

Secondary Outcomes (15)

• Efficacy Endpoint: Percent Change From Baseline at Week 24 for Various Lipid Parameters

  Baseline through Week 24

• Efficacy Endpoint: Percent Change From Baseline at Week 24 for Lp(a)

  Baseline through Week 24

• Percent Change From Baseline at All Other Time Points Through Week 104 for LDL-C

  Baseline through Week 104

• Percent Change From Baseline at All Other Time Points Through Week 104 for Non-HDL-C

  Baseline through Week 104

• Percent Change From Baseline at All Other Time Points Through Week 104 for TC

  Baseline through Week 104

Other Outcomes (3)

• Percent Change of Body Mass Index (BMI)

  Baseline through Week 104

• Lipid Accumulation in the Liver Over Time Measured by Nuclear Magnetic Resonance (NMR) at Baseline and at Week 24, Week 56 and at Week 104

  Baseline through Week 104

• Lipid Accumulation in the Liver Over Time Measured by Ultrasound at Baseline and at Week 24, Week 56 and at Week 104

  Baseline through Week 104

Study Arms (3)

Age 5-10 years

OTHER

Lomitapide dosing commenced with 2mg at week 1 for 8 Weeks,then increased to 5mg at Week 8±3 days, 10 mg at Week 12±3 days to the maximum allowable dose of 20 mg by Week 16±3 days or the MTD by Week 20±3 days based upon acceptable safety and tolerability criteria in addition to LDL C values.

Drug: Lomitapide

Age 11-15 years

OTHER

Lomitapide dosing commenced with 2mg at week 1 for 4 Weeks, then increased to 5mg at Week 4±3 days, 10 mg at Week 8±3 days, 20mg at Week 12±3 days to the maximum allowable dose of 40mg by Week 16±3 days or the MTD by Week 20±3 days based upon acceptable safety and tolerability criteria in addition to LDL C values.

Drug: Lomitapide

Age 16 to ≤17 years

OTHER

Lomitapide dosing commenced with 5mg at week 1 for 4 Weeks, then increased to 10mg at Week 4±3 days, 20 mg at Week 8±3 days, 40mg at Week 12±3 days to the maximum allowable dose of 60mg by Week 16±3 days or the MTD by Week 20±3 days based upon acceptable safety and tolerability criteria in addition to LDL C values.

Drug: Lomitapide

Interventions

Lomitapide DRUG

2mg,5mg, 10mg and 20mg capsules

Age 11-15 years; Age 16 to ≤17 years; Age 5-10 years

Eligibility Criteria

• Age: 5 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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 European Atherosclerosis Society (EAS) (Cuchel, Bruckert et al. 2014):
• 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
• 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)
• \>160 mg/dL (4.1 mmol/L, no documented cardiovascular disease \[CVD\]) or
• \>130 mg/dL (3.4 mmol/L, established CVD defined as aortic valve disease and/or coronary atherosclerosis)
• Body weight ≥15 kg or body mass index (BMI) and height both \>10th percentile according to World Health Organization (WHO) Growth Charts for Boys and Girls 5 to 19 Years of Age
• 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
• 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)
• 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
• 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.
• Patient must be in stable physical and mental health at screening

You may not qualify if:

• Other forms of primary hyperlipoproteinaemia and secondary causes of hypercholesterolaemia (e.g., nephrotic syndrome, hypothyroidism)
• 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
• 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 \[based on appropriate age and gender normal values\])
• Serum CK \>2 x ULN
• Chronic renal insufficiency with glomerular filtration rate (GFR) \<70 mL/min/1.73 m2 calculated using the Schwartz formula
• Uncontrolled hypertension (defined as mean systolic and/or diastolic blood pressure ≥95% of normal for age and sex) despite medical therapy
• New York Heart Association (NYHA) Class III or IV congestive heart failure
• Precocious/delayed puberty or endocrine disorder affecting growth (e.g., hypothyroidism, premature adrenarche)
• 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)
• Life expectancy predicted to be \<5 years
• History of a non skin malignancy (with the exception of cervical cancer in situ) within 3 years prior to enrolment
• 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
• Patient is a dependent of the sponsor, of the investigational team or his/her immediate family
• Pregnant or nursing women

Sponsors & Collaborators

• Amryt Pharma: lead

Study Sites (12)

Universtiats-Kinderlinik Heidelberg

Heidelberg, Baden-Wurttemberg, 69120, Germany

Location

University Hospital of Cologne

Cologne, 50937, Germany

Location

University Medical Center Hamburg-Eppendorf

Hamburg, 20246, Germany

Location

Chaim Sheba Medical Center

Ramat Gan, 52621, Israel

Location

U.O.C. Clinica Medica 1

Padua, Padua, 35128, Italy

Location

Bambino Gesù Children's Hospital,

Roma, 00165, Italy

Location

King Abdullah International Medical Research Centre (KAIMRC),

Riyadh, Saudi Arabia

Location

King Faisal Specialist Hospital

Riyadh, Saudi Arabia

Location

Hospital Universitari Sant Joan

Reus, Tarragona,, 43204, Spain

Location

Hospital Abente y Lago

A Coruña, 15006, Spain

Location

Hospital Clinico Universitario of Valencia

Valencia, 46010, Spain

Location

E.P.S. Fattouma Bourguiba Hospital

Monastir, 5000, Tunisia

Location

Related Publications (1)

• Masana L, Zambon A, Schmitt CP, Taylan C, Driemeyer J, Cohen H, Buonuomo PS, Alashwal A, Al-Dubayee M, Kholaif N, Diaz-Diaz JL, Maatouk F, Martinez-Hervas S, Mangal B, Lowe S, Cunningham T. Lomitapide for the treatment of paediatric patients with homozygous familial hypercholesterolaemia (APH-19): results from the efficacy phase of an open-label, multicentre, phase 3 study. Lancet Diabetes Endocrinol. 2024 Dec;12(12):880-889. doi: 10.1016/S2213-8587(24)00233-X. Epub 2024 Oct 16.

  PMID: 39426393 DERIVED

MeSH Terms

Conditions

Homozygous Familial Hypercholesterolemia

Interventions

BMS201038

Condition Hierarchy (Ancestors)

Hyperlipoproteinemia Type II; Lipid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hyperlipoproteinemias; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Limitations and Caveats

Lp(a) analysis was analysed locally as central analysis was only available from January 2022.

Results Point of Contact

• Title: Head of Clinical Operations
• Organization: Amryt Pharmaceuticals DAC

janet.boylan@amrytpharma.com

+35315180200

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 7, 2020
• First Posted: December 23, 2020
• Study Start: December 14, 2020
• Primary Completion: October 16, 2022
• Study Completion: June 6, 2024
• Last Updated: August 27, 2025
• Results First Posted: August 27, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

IL (1); ES (3); TU (1); SA (2); DE (3); IT (2)