Clinical trial NCT02890992: An 8-Week Dose-Finding Study to Evaluate the Efficacy and Safety of Alirocumab in Children and Adolescents With Heterozygous Familial Hypercholesterolemia
Official title: An 8-Week Open-Label, Sequential, Repeated Dose-Finding Study to Evaluate the Efficacy and Safety of Alirocumab in Children and Adolescents With Heterozygous Familial Hypercholesterolemia Followed by an Extension Phase
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hypercholesterolaemia
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
Collaborators: name: Regeneron Pharmaceuticals
First posted: 2016-09-07
Enrollment: 42
Sex: ALL
Minimum age (years): 8
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: Primary Objective:

To evaluate the effect of alirocumab on low-density lipoprotein cholesterol (LDL-C) levels after 8 weeks of treatment in heterozygous familial hypercholesterolemia (heFH) participants aged of 8 to 17 years, with LDL-C \>=130 milligrams per deciliter (mg/dL) (3.37 millimoles per litre \[mmol/L\]) on optimal stable daily dose of statin therapy +/- other lipid modifying therapies (LMTs) or a stable dose of non-statin LMTs in case of intolerance to statins for at least 4 weeks prior to the screening period.

Secondary Objective:

* To evaluate the safety and tolerability of alirocumab.
* To evaluate the pharmacokinetics profile of alirocumab.
* To evaluate the effects of alirocumab on other lipid parameters.

Detailed description: For Cohorts 1 to 3, a study duration of approximately 16-23 weeks (screening period: up to 6 (+1) weeks, open-label dose finding treatment period: 8 weeks, follow up period: 6-8 weeks).

For Cohort 4, a study duration of approximately 14-19 weeks (screening period up to 6 \[+1\] weeks, open-label dose finding treatment period: 12 weeks).

Optional extension period: up to a maximum of 2 years for the first participants enrolled in Cohorts 1 to 3, but a maximum of approximately 5 months for the first participants enrolled in Cohort 4.

For all participants who declined participation in the phase 3 study, their last alirocumab injection was on December 2018.

Eligibility criteria: Inclusion criteria :

* Children and adolescent male and female participants aged of 8 to 17 years at the time of signed informed consent. For Russia only: Male and female participants aged \>=12 and \<=17 years at the time of signed informed consent.
* Participants with diagnosis of heterozygous familial hypercholesterolemia (heFH) through genotyping or clinical criteria.
* Participants treated with optimal dose of statin +/- other LMT(s) or non-statin LMT(s) if statin intolerant at stable dose for at least 4 weeks prior to screening lipid sampling.
* Participants with calculated LDL-C greater than or equal to 130 mg/dL (\>=3.37 mmol/L) at the screening visit.
* Participants with body weight greater than or equal to 25 kg.
* Participants aged of 8 to 9 years to be at Tanner stage 1 and participants aged of 10 to 17 years to be at least at Tanner stage 2 in their development.
* A signed informed consent indicating parental permission with or without participant assent.

Exclusion criteria:

* Participant with secondary hyperlipidemia.
* Diagnosis of homozygous familial hypercholesterolemia.
* Participant who had received lipid apheresis treatment within 2 months prior to the screening period, or has plans to receive it during the study.
* Known history of type 1 or type 2 diabetes mellitus.
* Known history of thyroid disease.
* Known history of hypertension.
* Fasting triglycerides \>350 mg/dL (3.95 mmol/L).
* Severe renal impairment (i.e., estimated glomerular filtration rate \[eGFR\] \<30 mL/min/1.73 m\^2).
* Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>2 x upper limit of normal (ULN).
* Creatinine phosphokinase (CPK) \>3 x ULN.

The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Primary outcomes:
measure: Percent Change From Baseline in Calculated Low Density Lipoprotein Cholesterol (LDL-C) at Week 8
timeFrame: Baseline, Week 8
Secondary outcomes:
measure: Absolute Change From Baseline in Calculated Low Density Lipoprotein Cholesterol (LDL-C) at Week 8
timeFrame: Baseline, Week 8
measure: Percentage of Participants Achieving Calculated Low Density Lipoprotein Cholesterol (LDL-C) <130 mg/dL (3.37 mmol/L) at Week 8
timeFrame: At Week 8
measure: Percentage of Participants Achieving Calculated LDL-C <110 mg/dL (2.84 mmol/L) at Week 8
timeFrame: At Week 8
measure: Percent Change From Baseline in Calculated LDL-C at Week 12: Cohort 4
timeFrame: Baseline, Week 12
measure: Percent Change From Baseline in Apolipoprotein (Apo) B at Week 8
timeFrame: Baseline, Week 8
measure: Percent Change From Baseline in Non-High Density Lipoprotein (HDL-C) at Week 8
timeFrame: Baseline, Week 8
measure: Percent Change From Baseline in Total Cholesterol (Total-C) at Week 8
timeFrame: Baseline, Week 8
measure: Percent Change From Baseline in Lipoprotein(a) at Week 8
timeFrame: Baseline, Week 8
measure: Percent Change From Baseline in Fasting Triglyceride at Week 8
timeFrame: Baseline, Week 8
measure: Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at Week 8
timeFrame: Baseline, Week 8
measure: Percent Change From Baseline in Apolipoprotein A-1 at Week 8
timeFrame: Baseline, Week 8
measure: Absolute Change From Baseline in Apolipoprotein B at Week 8
timeFrame: Baseline, Week 8
measure: Absolute Change From Baseline in Non-High-Density Lipoprotein (Non-HDL-C) at Week 8
timeFrame: Baseline, Week 8
measure: Absolute Change From Baseline in Total Cholesterol (Total-C) at Week 8
timeFrame: Baseline, Week 8
measure: Absolute Change From Baseline in Lipoprotein(a) at Week 8
timeFrame: Baseline, Week 8
measure: Absolute Change From Baseline in HDL-C at Week 8
timeFrame: Baseline, Week 8
measure: Absolute Change From Baseline in Fasting Triglyceride at Week 8
timeFrame: Baseline, Week 8
measure: Absolute Change From Baseline in Apolipoprotein A-1 at Week 8
timeFrame: Baseline, Week 8
measure: Absolute Change From Baseline in Ratio Apolipoprotein B/Apolipoprotein A-1 at Week 8
timeFrame: Baseline, Week 8
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Investigational Site Number 8400002
state: Missouri
city: Charlotte
country: United States
facility: Investigational Site Number 8400005
state: North Carolina
city: Cincinnati
country: United States
facility: Investigational Site Number 8400001
state: Ohio
city: Quebec
country: Canada
facility: Investigational Site Number 1240001
city: Brno
country: Czechia
facility: Investigational Site Number 2030001
city: Praha 5 - Motol
country: Czechia
facility: Investigational Site Number 2030003
city: Zlin
country: Czechia
facility: Investigational Site Number 2030002
city: Bron Cedex
country: France
facility: Investigational Site Number 2500001
city: Amsterdam
country: Netherlands
facility: Investigational Site Number 5280001
city: Oslo
country: Norway
facility: Investigational Site Number 5780001
city: Kemerovo
country: Russian Federation
facility: Investigational Site Number 6430001
city: Saint-Petersburg
country: Russian Federation
facility: Investigational Site Number 6430004
city: Parow
country: South Africa
facility: Investigational Site Number 7100001
city: A Coruna
country: Spain
facility: Investigational Site Number 7240004
city: Madrid
country: Spain
facility: Investigational Site Number 7240001
city: Stockholm
country: Sweden
facility: Investigational Site Number 7520001
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
citation: Daniels S, Caprio S, Chaudhari U, Manvelian G, Baccara-Dinet MT, Brunet A, Scemama M, Loizeau V, Bruckert E. PCSK9 inhibition with alirocumab in pediatric patients with heterozygous familial hypercholesterolemia: The ODYSSEY KIDS study. J Clin Lipidol. 2020 May-Jun;14(3):322-330.e5. doi: 10.1016/j.jacl.2020.03.001. Epub 2020 Mar 28.