Homozygous Familial Hypercholesterolaemia (HoFH) Clinical Trial
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
| Verified date | April 2023 |
| Source | Amryt Pharma |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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 LLT (including 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)
| Status | Active, not recruiting |
| Enrollment | 46 |
| Est. completion date | April 30, 2024 |
| Est. primary completion date | October 16, 2022 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 5 Years to 17 Years |
| Eligibility | 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) - 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 - 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 - 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 Exclusion criteria - 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 |
| Country | Name | City | State |
|---|---|---|---|
| Germany | University Hospital of Cologne | Cologne | |
| Germany | University Medical Center Hamburg-Eppendorf | Hamburg | |
| Germany | Universtiats-Kinderlinik Heidelberg | Heidelberg | Baden-Wurttemberg |
| Israel | Chaim Sheba Medical Center | Ramat Gan, | |
| Italy | U.O.C. Clinica Medica 1 | Padova | Padua |
| Italy | Bambino Gesù Children's Hospital, | Roma | |
| Saudi Arabia | King Abdullah International Medical Research Centre (KAIMRC), | Riyadh | |
| Saudi Arabia | King Faisal Specialist Hospital | Riyadh | |
| Spain | Hospital Abente y Lago | A Coruña | |
| Spain | Hospital Universitari Sant Joan | Reus | Tarragona, |
| Spain | Hospital Clinico Universitario of Valencia | Valencia | |
| Tunisia | E.P.S. Fattouma Bourguiba Hospital | Monastir, |
| Lead Sponsor | Collaborator |
|---|---|
| Amryt Pharma |
Germany, Israel, Italy, Saudi Arabia, Spain, Tunisia,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Efficacy endpoint Percent change in LDL C | 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 104±1 week | |
| Primary | Safety endpoints AE reporting | Incidence, severity, and relatedness of AEs | Baseline through Week 104±1 week | |
| Secondary | Percent change from Baseline at Week 24±3 days for the following lipid parameters: TC, Non HDL C, VLDL C, TG, Lp(a), and apoB | Baseline through Week 104±1 week | ||
| Secondary | Percent change from Baseline at all other time points through Week 104±1 week for the following lipid parameters: LDL C, TC, Non HDL C, VLDL C, TG, Lp(a), and apo B | Baseline through Week 104±1 week | ||
| Secondary | • Change in LLT and LA from Week 24±3 days through Week 104±1 week | Baseline through Week 104±1 week | ||
| Secondary | • Total number and percent of patients achieving the EAS recommended target LDL C of <135 mg/dL (3.5 mmol/L) in paediatric HoFH patients at Week 24±3 days and at any time on study | Baseline through Week 104±1 week |