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

Sanofi

Status and phase

Completed

Phase 3

Conditions

Hypercholesterolemia

Treatments

Drug: Pravastatin

Drug: Atorvastatin

Drug: Cholestyramine

Drug: Lovastatin

Drug: Ezetimibe

Drug: Simvastatin

Drug: Rosuvastatin

Drug: Omega-3 fatty acids

Drug: Fenofibrate

Drug: Nicotinic acid

Drug: Alirocumab SAR236553 (REGN727)

Drug: Fluvastatin

Study type

Interventional

Funder types

Industry

Identifiers

NCT03510715

2017-002297-39 (EudraCT Number)

U1111-1200-2046 (Other Identifier)

EFC14660

Details and patient eligibility

About

Primary Objective:

To evaluate the efficacy of alirocumab (75 or 150 milligrams [mg] depending on body weight [BW]), administered every 2 weeks (Q2W), on low-density lipoprotein cholesterol (LDL-C) levels at Week 12 of treatment in children and adolescents with homozygous familial hypercholesterolemia (hoFH) of 8 to 17 years of age on top of background treatments.

Secondary Objectives:

To evaluate the efficacy of alirocumab after 24 and 48 weeks of treatment on LDL-C levels.
To evaluate the effects of alirocumab on other lipid parameters (eg, apolipoprotein B [Apo B], non-high density lipoprotein cholesterol [non-HDL-C], total cholesterol [Total-C], high density lipoprotein cholesterol [HDL-C], lipoprotein a [Lp (a)], triglycerides [TG], apolipoprotein A-1 [Apo A-1] levels) after 12, 24, and 48 weeks of treatment.
To evaluate the safety and tolerability of alirocumab up to 48 weeks of treatment.

Full description

The study duration was up to 62 weeks, which included (if needed) a run-in period of up to 4 weeks, a screening period of up to 2 weeks, a treatment period of up to 48 weeks, and a follow-up of 8 weeks.

Enrollment

18 patients

Sex

All

Ages

8 to 17 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion criteria :

Participants genetically diagnosed with hoFH.
Participants 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.
A signed informed consent indicating parental permission with or without participants assent.
For participants on apheresis, currently undergoing stable LDL apheresis therapy prior to the screening visit (Week -2) and had initiated apheresis treatment for at least 6 months.

Exclusion criteria:

Participants with LDL-C <130 milligram per deciliter [mg/dL] (3.37 millimoles per liter [mmol/L]) obtained during the screening period after the participant had been on stable apheresis procedure or LMT (i.e., stable optimal dose of statin ± other stable LMTs, or stable non statin LMTs in statin-intolerant participants) treatment for at least 4 weeks.
Participants with BW <25 kg.
Participants aged 8 to 9 years not at Tanner Stage 1 and participants aged of 10 to 17 years not at least at Tanner Stage 2 in their development.
Participants with uncontrolled Type 1 or 2 diabetes mellitus.
Participants with known uncontrolled thyroid disease.
Participants with uncontrolled hypertension.
Participants who will receive statin de novo during the run-in period.
Fasting triglycerides greater than (>) 350 mg/dL (3.95 mmol/L) at the screening visit.
Severe renal impairment (i.e., estimated glomerular filtration rate <30 milliliter per minute/1.73 meter square) at the screening visit.
Alanine aminotransferase or aspartate aminotransferase >2 * upper limit of normal (ULN) at the screening visit.
Creatine phosphokinase >3 * ULN at the screening visit.

The above information was not intended to contain all considerations relevant to a participants potential participation in a clinical trial.

Trial design

Primary purpose

Treatment

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

18 participants in 1 patient group

Alirocumab

Experimental group

Description:

Participants with BW less than (<) 50 kilograms (kg) received subcutaneous (SC) injection of alirocumab 75 mg Q2W for 48 weeks. Alirocumab dose was up-titrated to 150 mg Q2W from Week 12 in case of increase in BW with BW greater than or equal to [>=] 50 kg. Participants with BW >=50 kg received SC injection of alirocumab 150 mg Q2W for 48 weeks.

Treatment: