A trial to evaluate the Efficacy and Safety of Evinacumab in Paediatric Patients With Homozygous Familial Hypercholesterolemia

• Register: EUCTR
• Last refreshed on: 8 August 2022
• Main ID: EUCTR2019-001931-30-AT
• Date of registration: 03/03/2020
• Prospective Registration: Yes
• Primary sponsor: Regeneron Pharmaceuticals, Inc.
• Public title: A trial to evaluate the Efficacy and Safety of Evinacumab in Paediatric Patients With Homozygous Familial Hypercholesterolemia
• Scientific title: A Three-Part, Single-Arm, Open-Label Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Evinacumab in Pediatric Patients with Homozygous Familial Hypercholesterolemia
• Date of first enrolment: 17/08/2020
• Target sample size: 20
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2019-001931-30
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no
• Phase: Human pharmacology (Phase I): yes Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Austria, Netherlands, Taiwan, 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:
1. Diagnosis of functional HoFH by either genetic or clinical criteria as defined in the protocol
2. LDL-C >130 mg/dL at the screening visit
3. Body weight =15 kg
4. Receiving stable maximally tolerated therapy*at the screening visit
*Maximally tolerated therapy could include a daily statin.
5. Willing and able to comply with clinic visits and study-related procedures
6. Parent(s) or legal guardian(s) must provide the signed informed
consent form (ICF). Patients =5 years of age (or above age determined by the IRB/EC and in accordance with the local regulations and requirements) must also provide informed assent forms (IAFs) to enroll in the study, and sign and date a separate IAF or ICF signed by the parent(s)/legal guardian(s) (as appropriate based on local regulations and requirements)
Are the trial subjects under 18? yes
Number of subjects for this age range: 20
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Background pharmacologic LMT, nutraceuticals or over-the-counter (OTC) therapies known to affect lipids, at a dose/regimen that has not been stable for at least 4 weeks (8 weeks for PCSK9 inhibitors) before the screening visit and patient is unwilling to enter the run-in period
2. For patients entering Part A, unable to temporarily discontinue apheresis from the baseline visit through the week 4 visit
3. Receiving lipid apheresis, a setting (if applicable) and schedule that has not been stable for approximately 8 weeks before the screening visit or an apheresis schedule that is not anticipated to be stable over the duration of the treatment period (48 weeks).
4. Plasmapheresis within 8 weeks of the screening visit, or plans to undergo plasmapheresis during Part A or Part B
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 diabetes as defined in the protocol

Additional exclusion criteria apply


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

Health Condition(s) or Problem(s) studied

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

Homozygous familial hypercholesterolemia
MedDRA version: 21.0 Level: LLT Classification code 10020604 Term: Hypercholesterolemia System Organ Class: 100000004861

Intervention(s)

Product Name: Evinacumab
Product Code: REGN1500
Pharmaceutical Form: Solution for injection/infusion
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: 150-

Primary Outcome(s)

Secondary Objective: The secondary objective for Part A of the study is to evaluate the safety and tolerability of evinacumab administered intravenous (IV) in pediatric patients with HoFH

The secondary objectives for Part B of the study are:
- To evaluate the effect of evinacumab on other lipid parameters (ie, apolipoprotein B (Apo B), non-high-density lipoprotein cholesterol (non-HDL-C), total cholesterol (TC), lipoprotein a [Lp(a)]) in pediatric patients with HoFH
- To evaluate the safety and tolerability of evinacumab administered IV in pediatric patients with HoFH
- To assess the PK of evinacumab in pediatric patients with HoFH
- To assess the immunogenicity of evinacumab in pediatric patients with HoFH over time
- To evaluate patient efficacy by mutation status

Main Objective: The primary objective for Part A of the study is to assess the pharmacokinetics (PK) of evinacumab in pediatric patients with homozygous familial hypercholesterolemia (HoFH).

The primary objective for Part B of the study is to demonstrate a reduction of low-density lipoprotein cholesterol (LDL-C) by evinacumab in pediatric (5 to 11 years of age) patients with HoFH.

Primary end point(s): 1. Pharmacokinetic (PK) parameters for evinacumab (Part A)
2. Percent change in calculated low-density lipoprotein cholesterol (LDL-C) from baseline to week 24 (part B)

Timepoint(s) of evaluation of this end point: 1. Up to week 24
2. Week 24

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 1. Up to week 68
2.-7. Week 24
8.-10. Up to week 68

Secondary end point(s): 1. Incidence of treatment-emergent adverse events (TEAE) and other safety variables over time (Part A & B)
2. Percent change in Apoliprotein (Apo) B from baseline to week 24 (Part B)
3. Percent change in non-High-density lipoprotein cholesterol (HDL-C) from baseline to week 24 (Part B)
4. Percent change in total cholesterol (TC) from baseline to week 24 (Part B)
5. Proportion of patients with =50% reduction in calculated LDL-C at week 24 (Part B)
6. Percent change in calculated LDL-C from baseline to week 24 in patients who have negative/negative and null/null mutations (Part B)
7. Percent change in lipoprotein a [Lp(a)] from baseline to week 24 (Part B)
8. The absolute change in LDL-C at week 24 (Part B)
9. Concentrations of total evinacumab over time (Part B)
10. PK parameters (Part B)
11. Incidence and titer of treatment-emergent anti-drug antibodies (ADA) over time (Part B)

Secondary ID(s)

R1500-CL-17100

Source(s) of Monetary Support

Regeneron Pharmaceuticals, Inc.

Ethics review

Status: Approved
Approval date: 17/08/2020
Contact: