A study to evaluate the safety and efficacy of evinacumab in patients with Hereditary abnormal (high) cholesterol level

• Register: EUCTR
• Last refreshed on: 28 February 2019
• Main ID: EUCTR2017-001388-19-FR
• Date of registration: 24/01/2018
• Prospective Registration: Yes
• Primary sponsor: Regeneron Pharmaceuticals Inc.
• Public title: A study to evaluate the safety and efficacy of evinacumab in patients with Hereditary abnormal (high) cholesterol level
• Scientific title: A randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of evinacumab in patients with homozygous familial hypercholesterolemia
• Target sample size: 57
• Recruitment status: NA
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-001388-19
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Austria, Canada, Czech Republic, France, Germany, Greece, Italy, Netherlands, South Africa, Turkey, Ukraine, United States

Contacts

• Name: Clinical Trial Information
• Affiliation: Regeneron Pharmaceuticals, Inc.

• Name: Clinical Trial Information
• Affiliation: Regeneron Pharmaceuticals, Inc.

Key inclusion & exclusion criteria

Inclusion criteria:
Key inclusion criteria:
1. Male or female =12 years of age at the time of the screening visit
2. Diagnosis of functional HoFH
3. If undergoing LDL apheresis, must have initiated LDL apheresis at least 3 months prior to screening and must have been on a stable weekly or every other week schedule and/or stable settings for at least 8 weeks
4. Willing to consistently maintain his/her usual low fat or heart-healthy diet for the duration of the study

Note: Other protocol defined inclusion/exclusion criteria may apply.
Are the trial subjects under 18? yes
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 47
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Key exclusion criteria:
1. LDL-C level <70 mg/dL (1.81 mmol/L) at the screening visit.
2. Background medical LMT (if applicable) that has not been stable before the screening visit
3. Lipid-apheresis schedule (every 7 or 14 days)/apheresis settings (if applicable) that have not been stable for at least 8 weeks before the screening visit
4. Use of nutraceuticals or over-the-counter therapies known to affect lipids, at a dose/amount that has not been stable for at least 4 weeks prior to the screening visit
5. Presence of any clinically significant uncontrolled endocrine disease known to influence serum lipids or lipoproteins
6. Newly diagnosed (within 3 months prior to randomization visit) diabetes mellitus or poorly controlled (HbA1c >9%) diabetes
7. History of a MI, unstable angina leading to hospitalization, coronary artery bypass graft surgery, percutaneous coronary intervention, uncontrolled cardiac arrhythmia, carotid surgery or stenting, stroke, transient ischemic attack, valve replacement surgery, carotid revascularization, endovascular procedure or surgical intervention for peripheral vascular disease within 3 months prior to the screening visit
8. Pregnant or breastfeeding women
9. Sexually active women of child bearing potential (WOCBP), who are unwilling to practice a highly effective birth control method prior to the initial dose, during the study, and for 24 weeks after the last dose of study drug
10. Sexually active men who are unwilling to use forms of medically acceptable birth control during the study drug treatment period and for 24 weeks after the last dose of study drug

Note: Other protocol defined inclusion/exclusion criteria may apply.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Homozygous familial hypercholesterolemia
MedDRA version: 20.1 Level: LLT Classification code 10020604 Term: Hypercholesterolemia System Organ Class: 100000004861

Therapeutic area: Body processes [G] - Metabolic Phenomena [G03]

Intervention(s)

Product Name: Evinacumab (REGN1500)
Product Code: REGN1500
Pharmaceutical Form: Powder and solvent for solution for injection
INN or Proposed INN: Evinacumab
CAS Number: 1446419-85-7
Current Sponsor code: REGN1500
Other descriptive name: EVINACUMAB
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Powder and solvent for solution for injection
Route of administration of the placebo: Intravenous use

Trade Name: Praluent
Pharmaceutical Form: Solution for injection in pre-filled pen
INN or Proposed INN: ALIROCUMAB
CAS Number: 1245916-14-6
Other descriptive name: ALIROCUMAB
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-

Primary Outcome(s)

Secondary Objective: The secondary objectives of the study are:
• To evaluate the effect of evinacumab 15 mg/kg IV on other lipid parameters (ie, Apo B, non-HDL-C, total cholesterol [TC]) in patients with HoFH
• To evaluate the effect of evinacumab on LDL-C goal attainment
• To assess the effect of evinacumab on eligibility for apheresis (using German and US apheresis criteria)
• To evaluate the safety and tolerability of evinacumab 15 mg/kg in patients with HoFH
• To determine concentrations of evinacumab in patients with HoFH
• To evaluate the potential development of anti-evinacumab antibodies

Main Objective: The primary objective of the study is to demonstrate the reduction of LDL-C by evinacumab 15 mg/kg IV in comparison to placebo after 24 weeks in patients with HoFH.

Primary end point(s): The primary endpoint is the percent change in calculated LDL-C from baseline to week 24. The primary endpoint is defined as: 100x (calculated LDL-C value at week 24 - calculated LDL C value at baseline)/calculated LDL-C value at baseline.

Timepoint(s) of evaluation of this end point: week 24

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: week 24

Secondary end point(s): The key secondary endpoints are:
• The percent change in Apo B from baseline to week 24 (ITT estimand)
• The percent change in non-HDL-C from baseline to week 24 (ITT estimand)
• The percent change in TC from baseline to week 24 (ITT estimand)
• The proportion of patients with =30% reduction in calculated LDL-C at week 24 (ITT estimand)
• The proportion of patients with =50% reduction in calculated LDL-C at week 24 (ITT estimand)
• The proportion of patients with LDL-C <100 mg/dL [2.59 mmol/L] at week 24 (ITT estimand)
• The change in calculated LDL-C from baseline to week 24 (ITT estimand)
• The proportion of patients who meet EU apheresis eligibility criteria (see German Apheresis Working Group) at week 24 (ITT estimand)
• The proportion of patients who meet US apheresis eligibility criteria (see US [National Lipid Association] Lipid Apheresis Criteria) at week 24 (ITT estimand)

Refer to protocol for a full list.

Secondary ID(s)

2017-001388-19-DE

R1500-CL-1629

Source(s) of Monetary Support

Regeneron Pharmaceuticals, Inc.