AzTrials
AzTrials

Homozygous Familial Hypercholesterolaemia (HoFH)Phase 3NCT04681170

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

A Phase 3 study testing Lomitapide in people with Homozygous Familial Hypercholesterolaemia (HoFH), run by Amryt Pharma at 12 sites in 6 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 5 to 17 years
What is being tested?
Lomitapide
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
46 participants
Where
12 sitesin 6 countries
Study dates
14 Dec 2020to 6 Jun 2024
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 5 to 17 years
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • 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)
Show all 13Show fewer
  • 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

Who cannot join

  • 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
Show all 14Show fewer
  • 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

Trial locations and contacts

12 sites in 6 countries.

12 sites in 6 countries

Germany3 sites

  • University Hospital of Cologne

    Cologne, 50937

  • University Medical Center Hamburg-Eppendorf

    Hamburg, 20246

  • Universtiats-Kinderlinik Heidelberg

    Heidelberg, Baden-Wurttemberg, 69120

Other trials in Germany

Spain3 sites

  • Hospital Abente y Lago

    A Coruña, 15006

  • Hospital Universitari Sant Joan

    Reus, Tarragona,, 43204

  • Hospital Clinico Universitario of Valencia

    Valencia, 46010

Other trials in Spain

Italy2 sites

  • U.O.C. Clinica Medica 1

    Padova, Padua, 35128

  • Bambino Gesù Children's Hospital,

    Roma, 00165

Other trials in Italy

Saudi Arabia2 sites

  • King Abdullah International Medical Research Centre (KAIMRC),

    Riyadh

  • King Faisal Specialist Hospital

    Riyadh

Other trials in Saudi Arabia

Israel1 site

  • Chaim Sheba Medical Center

    Ramat Gan, 52621

Other trials in Israel

Tunisia1 site

  • E.P.S. Fattouma Bourguiba Hospital

    Monastir, 5000

Other trials in Tunisia

About this study

Official title: Phase III, Single Arm, Open Label, International, Multi Centre Study to Evaluate the Efficacy and Safety of Lomitapide in Paediatric Patients With Homozygous Familial Hypercholesterolaemia (HoFH) on Stable Lipid Lowering Therapy

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)
Read the detailed description

Lomitapide has been approved for use in adult patients with HoFH in the European Union (EU) and European Economic Area (EEA), United States of America (USA), Israel, Argentina, Canada, Colombia, and Japan. This study is designed to determine if lomitapide is effective and can be safely administered to paediatric patients with HoFH. If the efficacy and safety so far observed in adults is confirmed in paediatric patients, the potential exists to significantly lower low-density lipoprotein cholesterol (LDL-C) levels in paediatric patients with HoFH. Furthermore, the lower LDL-C levels may reduce atherosclerosis progression and would be expected to benefit these paediatric patients with HoFH.

A single arm, non comparator design has been selected due to the rarity of the disease and because the evaluation of safety variables such as growth and sexual maturation requires longer term observation than would be feasible in the context of a placebo controlled study.

To mitigate the disadvantages of a single arm design, the study includes a Run in Period of at least 6 weeks during which current lipid lowering therapy (LLT) (including lipoprotein apheresis (LA), when applicable) will be stabilised to establish baseline levels allowing each patient to serve as his/her own control. Patients will also remain on stable LLT (including LA, when applicable) during the Efficacy Phase of the study through Week 24±3 days.

Being tested
Lomitapide
Medical subject headings
Homozygous Familial Hypercholesterolemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LomitapideDrug

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

Study groups in NCT04681170
Study groupRoleWhat they receive
Age 5-10 yearsOtherLomitapide 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.
Receives: Drug: Lomitapide
Age 11-15 yearsOtherLomitapide 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.
Receives: Drug: Lomitapide
Age 16 to ≤17 yearsOtherLomitapide 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.
Receives: Drug: Lomitapide

What is being measured

The primary outcome is the main question the study is designed to answer.

  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)

    Measured: Baseline through Week 24

Secondary outcomes (15)

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

    To evaluate the efficacy of lomitapide, as defined by the percent change of the following lipid parameters at the maximum tolerated dose (MTD):

    • Non-high-density lipoprotein cholesterol (Non-HDL-C)
    • Total cholesterol (TC)
    • Very-low-density lipoprotein cholesterol (VLDL-C)
    • Apolipoprotein B (Apo B)
    • TG (Triglycerides)

    Measured: Baseline through Week 24

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

    To evaluate the efficacy of lomitapide, as defined by the percent change in Lp(a) at the maximum tolerated dose (MTD)

    Measured: Baseline through Week 24

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

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

    Measured: Baseline through Week 104

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

    To evaluate the efficacy of lomitapide, as defined by the percent change in Non-HDL-C at the maximum tolerated dose (MTD)

    Measured: Baseline through Week 104

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

    To evaluate the efficacy of lomitapide, as defined by the percent change in TC at the maximum tolerated dose (MTD)

    Measured: Baseline through Week 104

  6. Percent Change From Baseline at All Other Time Points Through Week 104 for VLDL-C

    To evaluate the efficacy of lomitapide, as defined by the percent change in VLDL-C at the maximum tolerated dose (MTD)

    Measured: Baseline through Week 104

  7. Percent Change From Baseline at All Other Time Points Through Week 104 for Apo B

    To evaluate the efficacy of lomitapide, as defined by the percent change in apo B at the maximum tolerated dose (MTD)

    Measured: Baseline through Week 104

  8. Percent Change From Baseline at All Other Time Points Through Week 104 for TG

    To evaluate the efficacy of lomitapide, as defined by the percent change in TG at the maximum tolerated dose (MTD)

    Measured: Baseline through Week 104

  9. Percent Change From Baseline at All Other Time Points Through Week 104 for Lipoprotein(a) (Lp(a))

    To evaluate the efficacy of lomitapide, as defined by the percent change in Lp(a) at the maximum tolerated dose (MTD)

    Measured: Baseline through Week 104

  10. Percent Change in TC/HDL-C Ratio From Baseline at All Other Time Points to Week 104

    To evaluate the efficacy of lomitapide, as defined by the percent change in TC/HDL-C ratio at the maximum tolerated dose (MTD)

    Measured: Baseline through Week 104

  11. Percent Change in HDL-C From Baseline at All Other Time Points to Week 104

    To evaluate the efficacy of lomitapide, as defined by the percent change in HDL-C at the maximum tolerated dose (MTD)

    Measured: Baseline through Week 104 week

  12. Change in LLT From Week 28 Through Week 104

    To evaluate the efficacy of lomitapide, as defined by the change in background lipid lowering therapy

    Measured: Week 28 through Week 104

  13. Change in LA From Week 28 Through Week 104

    To evaluate the efficacy of lomitapide, as defined by the change in lipoprotein apheresis

    Measured: Week 28 through Week 104

  14. Number and Percentage of Patients Achieving European Atherosclerosis Society (EAS) Recommended Target (2013) of LDL-C at Any Timepoint Between Baseline and Week 24

    To evaluate the efficacy of lomitapide, as defined by the number and percentage of patients achieving EAS recommended target (2013) of LDL-C

    Measured: Baseline through Week 24

  15. Number and Percentage of Patients Achieving EAS Recommended Target (2013) of LDL-C at Any Time in the Study

    To evaluate the efficacy of lomitapide, as defined by the number and percentage of patients achieving EAS recommended target (2013) of LDL-C

    Measured: Baseline through Week 104

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Dec 2020
  2. Study start14 Dec 2020
  3. Primary completion16 Oct 2022
  4. Study completion6 Jun 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
46 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04681170
Sponsor's protocol ID
APH-19
Status last verified
Jun 2025
First submitted
7 Dec 2020
Last updated
27 Aug 2025
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 39426393

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Lomitapide in people with Homozygous Familial Hypercholesterolaemia (HoFH), run by Amryt Pharma at 12 sites in 6 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 12 sites in Germany, Spain, Italy, Saudi Arabia, Israel and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 27 Aug 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Efficacy Endpoint: Percent Change in Low-density Lipoprotein Cholesterol (LDL C) at Week 24 Compared to Baseline (time frame: Baseline through Week 24). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04681170, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Aug 2025.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in