Study to evaluate the safety, tolerability, and efficacy of LOmitapide for the treatment of patients with Familial CHylomicroNEmia Syndrome
- Conditions
- Familial Chylomicronemia SyndromeMedDRA version: 20.0Level: PTClassification code 10058108Term: DyslipidaemiaSystem Organ Class: 10027433 - Metabolism and nutrition disordersTherapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]
- Registration Number
- EUCTR2018-002911-80-IT
- Lead Sponsor
- PRM|21218
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 20
1.Written informed consent
2.Age = 18 years at time of informed consent
3.History of chylomicronemia as evidenced by documentation of lactescent serum or documentation of fasting TG measurement = 885 mg/dl (10 mmol/L)
4.A diagnosis of Familial Chylomicronemia Syndrome by documentation of at least one of the following: confirmed homozygote, compound heterozygote or double heterozygote for known loss-of-function mutations in genes causing FCS
5.Fasting TG = 750 mg/dl (8.4 mmol/L) at screening
6.History of pancreatitis
7.Willing to follow a diet comprising = 20 g fat per day during the study con quanto riportato a pag. 21 Screening procedures include also dietary counseling with regard to low-fat diet (=20% energy from fat) and to avoid alcohol completely while receiving Lomitapide
8.Satisfy one of the following:
•Females: non-pregnant and non-lactating; surgically sterile, post-menopausal, abstinent, or if engaged in sexual relations of child-bearing potential, patient is using an acceptable contraceptive method
•Males: Surgically sterile, abstinent or if engaged in sexual relations with a female of child-bearing potential, patient is utilizing an acceptable contraceptive method
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 17
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 3
1.Diabetes mellitus with any of the following: newly diagnosed within 12 weeks of screening; HbA1c = 9.0% at screening; recent change in anti-diabetic pharmacotherapy; anticipated need to change dose or type of medication during the treatment period of the study; current use of GLP-1 agonists.
2.Severe hypertriglyceridemia other than due to FCS.
3.Active pancreatitis within 4 weeks prior to screening.
4.History within 6 months of screening of acute or unstable cardiac ischemia, stroke, transient ischemic attack or unstable congestive cardiac failure requiring a change in medication or major surgery within 3 months of screening.
5.Any of the following laboratory values at screening: total bilirubin > upper limit of normal (ULN); AST > 2.0 x ULN; ALT > 2.0 x ULN; persistently positive for protein on urine dipstick; persistently positive for blood or urine dipstick; estimated creatinine clearance calculated according to the formula of Cockcroft and Gault < 50 mL/min.
6.Uncontrolled hypertension (BP > 160/100 mmHg).
7.History of bleeding diathesis or coagulopathy or clinically significant abnormality in coagulation parameters at screening.
8.History of heart failure with NYHA greater than Class II.
9.Active infection requiring systemic antiviral or antimicrobial therapy that will not be completed prior to begin treatment with Lomitapide (Baseline Visit).
10.Known history of or positive test for human immunodeficiency virus (HIV), hepatitis C or chronic hepatitis B.
11.Malignancy within 5 years, except for basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix that has been successfully treated.
12.Treatment with another investigational drug, biological agent, or device within one month of screening, or 5 half-lives of investigational agent, whichever is longer.
13.Unwilling to comply with lifestyle requirements.
14. Known lactose intolerance.
15. Use of the following:
•Statins, omega-3 fatty acids or fibrates unless on a stable dose for at least 3 months prior to screening and dose and regimen expected to remain constant during the treatment period. Patients taking omega-3 fatty acids should make every effort to remain on the same brand throughout the study
•Nicotinic acid or derivatives of nicotinic acid within 4 weeks prior to screening
•Systemic corticosteroids or anabolic steroids within 6 weeks prior to screening unless approved by the Investigator
•Atypical antipsychotic medications unless on a stable dose for at least 4 weeks prior to screening and dose and regimen expected to remain constant during the treatment period
•Glybera gene therapy within 2 years prior to screening
•Oral anticoagulants (e.g., warfarin, dabigatran, rivaroxaban, and apixaban) unless on a stable dose for at least 4 weeks prior to screening and regular clinical monitoring is performed
•Tamoxifen, estrogens or progestins unless on a stable dose for at least 4 months prior to screening and dose and regimen expected to remain constant during the treatment period
•Plasma apheresis within 4 weeks prior to screening or planned during the study
•Any of the medication unless stable at least 4 weeks prior to screening
16.Blood donation of 50 to 499 mL within 30 days of screening or of > 499 mL within 60 days of screening
17.Have any other conditions, which, in the opinion of the Investigators or the Sponsor would make the patient unsuitable for inclusion, or could interfere with the patient participating in or completi
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The primary objective of the study is to evaluate the efficacy of Lomitapide in combination with other lipid lowering therapy in patients with Familial Chylomicronemia Syndrome (FCS).;Secondary Objective: The secondary objectives of the study are to evaluate:<br>1. other lipid parameters<br>2. long-term safety of Lomitapide<br>3. hepatic fat and liver stiffness and Chylomicron kinetics in combination with other lipid lowering agents in patients with FCS during the full length of the clinical study.;Primary end point(s): Percent change in tryglicerides (TG) at the maximum tolerated dose compared to baseline after 26 weeks of treatment in combination with other lipid lowering therapy in patients with Familial Chylomicronemia Syndrome (FCS).;Timepoint(s) of evaluation of this end point: 26 weeks
- Secondary Outcome Measures
Name Time Method Secondary end point(s): Other lipid parameters, hepatic fat and liver stiffness and Chylomicron kinetics of Lomitapide in combination with other lipid lowering agents in term of changes at 26 weeks from baseline.<br>In particular we will assess:<br>a)Percent change in TC, non-HDL-C, LDL-C, VLDL, Lp(a), as well as apolipoproteins B and A1.<br>b)Safety of Lomitapide in patients with FCS assessed by changes in laboratory parameters, electrocardiogram, physical examinations and weight.<br>c)Record of episodes of pancreatitis<br>d)Change in hepatic fat liver stiffness measured by MRI and/or Transient Elastography (Fibroscan).<br>e)Chylomicron kinetics.;Timepoint(s) of evaluation of this end point: 26 weeks