Heterozygous Familial Hypercholesterolaemia MedDRA version: 14.1 Level: LLT Classification code 10057099 Term: Heterozygous familial hypercholesterolaemia System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Product Name: eprotirome
Product Code: KB2115
Pharmaceutical Form: Tablet
INN or Proposed INN: eprotirome
CAS Number: CAS355129-15
Current Sponsor code: KB2115
Other descriptive name: BMS356384
Concen
Sponsors
Karo Bio AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1)Patients with confirmed HeFH who are 18 years of age or older, understand the study procedures and agree to participate in the study by giving written informed consent at Visit 1 and must have: a) Presence of clinical atherosclerotic disease that confers high risk for CAD events together with an LDL-C >2 mmol/L (>80 mg/dL) at Visit 2, based on one or more of the following; or b) Presence of at least 2 risk factors for CVD (other than the HeFH diagnosis) together with an LDL-C >2.5 mmol/L (>100 mg/dL) at Visit 2: 2) Patients should be on an optimal standard of care, defined as being on a stable dose of statin (at least half of the maximum dose of either rosuvastatin, atorvastatin, or simvastatin) with or without ezetimibe for at least 8 weeks prior to randomisation. If lower doses of rosuvastatin, atorvastatin, or simvastatin or any dose of fluvastatin or pravastatin are used the reasons must be clearly documented. 3) Women must not be pregnant or lactating. Women of childbearing potential must use a medically acceptable form of contraception at least 4 weeks prior to the start of the study and for at least 4 weeks after the patient’s last study visit. Subjects who are on systemic hormonal contraceptives must agree to use an additional method of contraception (barrier method). 4) Diabetes Mellitus (Type 1 and Type 2) for Type 2 (only metformin, sulfonylureas, alpha-glucosidase inhibitors or DPP-4s as diabetic medications are allowed) 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 1050 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1) Other dyslipidaemic or metabolic disorders that could affect the evaluation of eprotirome in HeFH, such as increased serum TG >4.5 mmol/L, HbA1c >8.5%, secondary dyslipidaemia or ongoing or planned apharesis 2) cardiac diseases that may interfere with the safety evaluation of eprotirome, such as congestive heart failure (NYHA III and IV), planned percutaneous coronary intervention, coronary artery bypass surgery, uncontrolled hypertension (defined as systolic blood pressure equal to or more than 160 mmHg or diastolic blood pressure equal to or more than 100 mmHg) or evidence of cardiac electrophysiologic instability including uncontrolled sick sinus syndrome, sino-atrial or atrioventricular block, ventricular arrhythmias, uncontrolled atrial fibrillation/flutter or uncontrolled supraventricular tachycardia with a ventricular response heart rate (>100 bpm) or a QTcF >450 ms 3) Previous stroke (includes definite or presumed cerebral ischaemia/infarction) 4) No other lipid-lowering medication with the exception of statins and ezetimibe are allowed 5) Patients with disturbed thyroid function, thyrotoxicosis, taking thyroid hormone or anti-thyroid medication are excluded 6) Drugs known to affect thyroid function tests are also prohibited 7) Patients with liver dysfunction such as: AST or ALT or ALP >1.5 x ULN, total bilirubin >ULN, active hepatobiliary disease, cholestasis, or serologic evidence of past or active hepatitis B or hepatitis C, acquired immune deficiency syndrome, positive HIV, substantial consumption of alcohol or drug abuse 8) Patients with serum creatinine >160 mmol/L or unexplained serum creatine kinase >3 x ULN 9) Patients on oral anticoagulant therapy other than vitamin K antagonists and anti-platelets agents 10) Rheumatoid arthritis; history of cancer, history of or current primary or secondary adrenal insufficiency or any other condition that in the opinion of the investigator confound the evaluation and interpretation of efficacy and or safety data.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to compare the efficacy of eprotirome 50 µg and eprotirome 100 µg versus placebo in terms of the percent change in LDL-C from baseline to Week 12 in HeFH patients with CAD, or who are at high risk for CAD, and who are on optimal standard of care consisting of a statin with or without ezetimibe;Secondary Objective: •To compare the efficacy of eprotirome 50µg and 100 µg versus placebo in terms of the percent change in LDL-C from baseline to Week 28, 52, 76, and 100;in TG, HDL C, non-HDL-C, TC, (apo) A-I, apo B, Lp[a], and markers for inflammation (eg, hsCRP) from baseline to Week 12, 28, 52, 76, and 100; •To compare the efficacy of eprotirome 50 µg and 100 µg versus placebo in terms of the proportion of patients who have a reduction in LDL-C of >15% from baseline to Week 12; •To monitor the systemic exposure to the nitrated reaction product KB42899 in the population through sparse sampling and explore the pharmacokinetics (PK) of KB42899 and eprotirome through rich sampling in selected cases; •Evaluation for knee-joint function and symptoms using a PRO questionnaire, KOOS •Long term safety and tolerability of eprotirome;Primary end point(s): Efficacy: The percent change in LDL-C from baseline to Week 12.;Timepoint(s) of evaluation of this end point: Week 12 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy: Percent change in LDL-C from baseline to Week 28, Week 52, Week 76, and Week 100; Percent change in TG, HDL-C, non-HDL-C, TC, apo A-I, apo B, Lp(a), and hsCRP from baseline to Week 12, Week 28, Week 52, Week 76, and Week 100; and Proportion of patients with an LDL-C reduction from baseline of more than 15% at Week 12.;Timepoint(s) of evaluation of this end point: Week 12, Week 28, Week 76 and Week 100. | — |
Countries
Austria, Czech Republic, Denmark, India, Israel, Netherlands, Norway, Russian Federation, South Africa, Spain, Sweden, United Kingdom
Contacts
Public ContactRegulatory Affairs Director
Karo Bio AB
Outcome results
None listed