An Efficacy and Safety Study of Alirocumab in Children and Adolescents with Homozygous Familial Hypercholesterolemia

• Register: EUCTR
• Last refreshed on: 10 January 2022
• Main ID: EUCTR2017-002297-39-NO
• Date of registration: 15/05/2018
• Prospective Registration: Yes
• Primary sponsor: Sanofi-Aventis Recherche & Développement
• Public title: An Efficacy and Safety Study of Alirocumab in Children and Adolescents with Homozygous Familial Hypercholesterolemia
• Scientific title: An Open-Label Study to Evaluate the Efficacy and Safety of Alirocumab in Children and Adolescents with Homozygous Familial Hypercholesterolemia
• Date of first enrolment: 19/09/2018
• Target sample size: 50
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-002297-39
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: no 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): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Austria, Brazil, Bulgaria, Canada, Denmark, France, Italy, Mexico, Netherlands, Norway, Russian Federation, Slovenia, Spain, Taiwan, Turkey, United States

Contacts

• Name: Clinical Study Unit
• Affiliation: Sanofi Norge AS

• Name: Clinical Study Unit
• Affiliation: Sanofi Norge AS

Key inclusion & exclusion criteria

Inclusion criteria:
-Patients genetically diagnosed with homozygous familial hypercholesterolemia (hoFH).
-Patients treated with optimal dose of statin +/- other lipid modifying therapies (LMTs), or non-statin LMTs if statin-intolerant at stable dose(s) for at least 4 weeks prior to screening lipid sample.
-A signed informed consent indicating parental permission with or without patient assent.
-For patients on apheresis, currently undergoing stable low-density lipoprotein (LDL) apheresis therapy prior to the screening and have initiated apheresis treatment for at least 6 months.
Are the trial subjects under 18? yes
Number of subjects for this age range: 50
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:
-Patients with low-density lipoprotein - cholesterol (LDL-C) less than 130 mg/dL (3.37 mmol/L) obtained during the screening period after the patient has been on stable apheresis procedure or lipid modifying therapy (LMT) (i.e., stable optimal dose of statin ± other stable LMTs, or stable non statin LMTs in statin-intolerant patients) treatment for at least 4 weeks.
-Patients with body weight less than 25 kg.
-Patients aged 8 to 9 years not at Tanner Stage 1 and patients aged of 10 to 17 years not at least at Tanner Stage 2 in their development.
-Patients with uncontrolled Type 1 or 2 diabetes mellitus.
-Patients with known uncontrolled thyroid disease.
-Patients with uncontrolled hypertension.
-Fasting triglycerides >350 mg/dL.
-Severe renal impairment (i.e., estimated glomerular filtration rate [eGFR] <30 mL/min/1.73m^2) at the screening visit.
-Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2 x upper limit of normal (ULN).
-Creatine phosphokinase (CPK) >3 x ULN.


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

Health Condition(s) or Problem(s) studied

Homozygous Familial Hypercholesterolemia
MedDRA version: 20.0 Level: PT Classification code 10020603 Term: Hypercholesterolaemia System Organ Class: 10027433 - Metabolism and nutrition disorders

Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

Intervention(s)

Product Name: Alirocumab
Product Code: SAR236553
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: Alirocumab
CAS Number: 1245916-14-6
Current Sponsor code: SAR236553 (RGN727)
Other descriptive name: ALIROCUMAB
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 75-
Pharmaceutical form of the placebo: Solution for infusion in pre-filled syringe
Route of administration of the placebo: Subcutaneous use

Product Name: Alirocumab
Product Code: SAR236553
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: Alirocumab
CAS Number: 1245916-14-6
Current Sponsor code: SAR236553 (RGN727)
Other descriptive name: ALIROCUMAB
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 150-
Pharmaceutical form of the placebo: Solution for infusion in pre-filled syringe
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Primary end point(s): Percent change in LDL-C (pre-apheresis, if applicable) from baseline to Week 12, using all LDL-C values (pre-apheresis, if applicable) regardless of adherence to treatment.

Secondary Objective: -To evaluate the efficacy of alirocumab after treatment on LDL-C levels.
-To evaluate the effects of alirocumab on other lipid parameters.
-To evaluate the safety and tolerability of alirocumab.

Main Objective: To evaluate the efficacy of alirocumab administered every 2 weeks (Q2W), on low-density lipoprotein cholesterol (LDL-C) levels of treatment in children with homozygous familial hypercholesterolemia (hoFH) 8 to 17 years of age on top of background treatments.

Timepoint(s) of evaluation of this end point: From baseline to Week 12

Secondary Outcome(s)

Secondary end point(s): 1. Percent change in LDL-C (pre-apheresis, if applicable) from baseline to Week 12, using all LDL-C values during the treatment period.
2. Percent change in LDL-C (pre-apheresis, if applicable).
3. Percent change in apolipoprotein B (Apo B) (pre-apheresis, if applicable).
4. Percent change in non-high density lipoprotein cholesterol (non-HDL-C) (pre-apheresis, if applicable).
5. Percent change in total cholesterol (total-C) (pre-apheresis, if applicable).
6. Percent change in lipoprotein (a) (Lp(a)) (pre-apheresis, if applicable).
7. Percent change in high-density lipoprotein cholesterol (HDL-C) (pre-apheresis, if applicable).
8. Percent change in fasting triglycerides (TG) (pre-apheresis, if applicable).
9. Percent change in apolipoprotein A1 (Apo A-1) (pre-apheresis, if applicable).
10. Proportion of patients with =15% reduction in LDL-C (pre-apheresis, if applicable).
11. Absolute change in LDL-C.
12. Number of patients with adverse events.
13. Tanner stage : the Tanner stage will be measured to assess stages of pubertal development.

Timepoint(s) of evaluation of this end point: 1. From baseline to Week 12
2. From baseline to Weeks 24 and 48
3. From baseline to Week 12, to Week 24, and to Week 48
4. From baseline to Week 12, to Week 24, and to Week 48
5. From baseline to Week 12, to Week 24, and to Week 48
6. From baseline to Week 12, to Week 24, and to Week 48
7. From baseline to Week 12, to Week 24, and to Week 48
8. From baseline to Week 12, to Week 24, and to Week 48
9. From baseline to Week 12, to Week 24, and to Week 48
10. From baseline to Weeks 12, 24 and 48
11. From baseline to Weeks 12, 24 and 48
12. Up to Week 62
13. At Weeks 24, 24, and 48

Secondary ID(s)

EFC14660

Source(s) of Monetary Support

Sanofi-Aventis Recherche & Développement

Ethics review

Status: Approved
Approval date: 19/09/2018
Contact:

Results

• Results available: Yes
• Date Posted: 28/08/2020
• Date Completed: 17/02/2020
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2017-002297-39/results