Clinical trial NCT03510715: An Efficacy and Safety Study of Alirocumab in Children and Adolescents With Homozygous Familial Hypercholesterolemia
Official title: An Open-Label Study to Evaluate the Efficacy and Safety of Alirocumab in Children and Adolescents With Homozygous Familial Hypercholesterolemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hypercholesterolemia
Keywords: Pediatrics, Homozygous Familial Hypercholesterolemia, Alirocumab, PCSK9 inhibitor, Low-density Lipoprotein Cholesterol (LDL-C)
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
Collaborators: name: Regeneron Pharmaceuticals
First posted: 2018-04-27
Enrollment: 18
Sex: ALL
Minimum age (years): 8
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility 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.

Primary outcomes:
measure: Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12: Intent-to-Treat (ITT) Analysis
timeFrame: Baseline to Week 12
Secondary outcomes:
measure: Percent Change From Baseline in Low-Density Lipoprotein Cholesterol at Week 12: On-treatment Analysis
timeFrame: Baseline to Week 12
measure: Percent Change From Baseline in Low-Density Lipoprotein Cholesterol at Weeks 24 and 48: ITT Analysis/On-treatment Analysis
timeFrame: Baseline to Weeks 24 and 48
measure: Percent Change From Baseline in Apolipoprotein (Apo) B at Weeks 12, 24 and 48: ITT Analysis/On-treatment Analysis
timeFrame: Baseline to Weeks 12, 24 and 48
measure: Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Weeks 12, 24 and 48 - ITT Analysis/On-treatment Analysis
timeFrame: Baseline to Weeks 12, 24 and 48
measure: Percent Change From Baseline in Total Cholesterol (Total-C) at Weeks 12, 24 and 48: ITT Analysis/On-treatment Analysis
timeFrame: Baseline to Weeks 12, 24 and 48
measure: Percent Change From Baseline in Lipoprotein a (Lp) (a) at Weeks 12, 24 and 48: ITT Analysis/On-treatment Analysis
timeFrame: Baseline to Weeks 12, 24 and 48
measure: Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at Weeks 12, 24 and 48: ITT Analysis/On-treatment Analysis
timeFrame: Baseline to Weeks 12, 24 and 48
measure: Percent Change From Baseline in Fasting Triglycerides (TG) at Weeks 12, 24 and 48: ITT Analysis/On-treatment Analysis
timeFrame: Baseline to Weeks 12, 24 and 48
measure: Percent Change From Baseline in Apolipoprotein A1 (Apo A1) at Weeks 12, 24 and 48: ITT Analysis/On-treatment Analysis
timeFrame: Baseline to Weeks 12, 24 and 48
measure: Percentage of Participants Reporting >=15 Percent (%) Reduction in LDL-C Level at Weeks 12, 24 and 48: ITT Analysis/On-treatment Analysis
timeFrame: Baseline to Weeks 12, 24 and 48
measure: Absolute Change From Baseline in LDL-C Level at Weeks 12, 24 and 48: ITT Analysis/On-treatment Analysis
timeFrame: Baseline to Weeks 12, 24 and 48
measure: Number of Participants With Tanner Staging at Baseline, Weeks 12, 24 and 48
timeFrame: Baseline, Weeks 12, 24 and 48
Other outcomes:
Locations:
city: Sao Paulo
country: Brazil
facility: Investigational Site Number 0760001
city: Quebec
country: Canada
facility: Investigational Site Number 1240001
city: Viborg
country: Denmark
facility: Investigational Site Number 2080001
city: Oaxaca
country: Mexico
facility: Investigational Site Number 4840006
city: Amsterdam
country: Netherlands
facility: Investigational Site Number 5280001
city: Kemerovo
country: Russian Federation
facility: Investigational Site Number 6430002
city: Ljubljana
country: Slovenia
facility: Investigational Site Number 7050001
city: A Coruna
country: Spain
facility: Investigational Site Number 7240001
city: Taipei
country: Taiwan
facility: Investigational Site Number 1580001
city: Izmir
country: Turkey
facility: Investigational Site Number 7920001
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
citation: Bruckert E, Caprio S, Wiegman A, Charng MJ, Zarate-Morales CA, Baccara-Dinet MT, Manvelian G, Ourliac A, Scemama M, Daniels SR. Efficacy and Safety of Alirocumab in Children and Adolescents With Homozygous Familial Hypercholesterolemia: Phase 3, Multinational Open-Label Study. Arterioscler Thromb Vasc Biol. 2022 Dec;42(12):1447-1457. doi: 10.1161/ATVBAHA.122.317793. Epub 2022 Nov 3.