Clinical trial NCT03510884: An Efficacy and Safety Study of Alirocumab in Children and Adolescents With Heterozygous Familial Hypercholesterolemia
Official title: A Randomized, Double-Blind, Placebo-Controlled Study Followed by an Open Label Treatment Period to Evaluate the Efficacy and Safety of Alirocumab in Children and Adolescents With Heterozygous Familial Hypercholesterolemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hypercholesterolaemia
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
Collaborators: name: Regeneron Pharmaceuticals
First posted: 2018-04-27
Enrollment: 153
Sex: ALL
Minimum age (years): 8
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Primary Objective:

To evaluate the efficacy of alirocumab administered every 2 weeks (Q2W) and every 4 weeks (Q4W) versus placebo after 24 weeks of double-blind (DB) treatment on low-density lipoprotein cholesterol (LDL-C) levels in participants with heterozygous familial hypercholesterolemia (heFH) 8 to 17 years of age 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.

Secondary Objectives:

* To evaluate the efficacy of alirocumab versus placebo on LDL-C levels.
* To evaluate the effects of alirocumab versus placebo on other lipid parameters.
* To evaluate the safety and tolerability of alirocumab in comparison with placebo.
* To evaluate the efficacy, safety, and tolerability of alirocumab after open label treatment.
* To evaluate the development of anti-alirocumab antibodies.

Detailed description: The study duration was approximately up to 110 weeks (run-in period \[if needed\]: up to 4 weeks \[+2 days\], screening period: up to 2 weeks \[+5 days\], double-blind treatment period: 24 weeks, open label (OL) treatment period: 80 weeks).

Eligibility criteria: Inclusion criteria:

* Children and adolescent male and female participants 8 to 17 years of age at the time of signed informed consent.
* Participants with diagnosis of 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 except for participants who have previously participated in the DFI14223 (NCT02890992) study.
* A signed informed consent indicating parental permission with or without participant assent.

Exclusion criteria:

* Participant with body weight \< 25 kg.
* Participants aged of 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 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.
* Participants with uncontrolled type 1 or type 2 diabetes mellitus.
* Participants with known uncontrolled thyroid disease.
* Participants with uncontrolled hypertension.
* Fasting triglycerides greater than (\>) 350 mg/dL (3.95 mmol/L).
* Severe renal impairment (ie, estimated glomerular filtration rate \<30 mL/min/1.73 m\^2).
* Alanine aminotransferase or aspartate aminotransferase \>2\*upper limit of normal (ULN).
* Creatinine phosphokinase (CPK) \>3\*ULN.

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

Primary outcomes:
measure: DB Period: Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 24: Intent-to-treat (ITT) Estimand
timeFrame: Baseline, Week 24
Secondary outcomes:
measure: DB Period: Percent Change From Baseline in Low Density Lipoprotein Cholesterol at Week 12: ITT Estimand
timeFrame: Baseline, Week 12
measure: DB Period: Percent Change From Baseline in Apolipoprotein B (Apo B) at Week 24: ITT Estimand
timeFrame: Baseline, Week 24
measure: DB Period: Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 24: ITT Estimand
timeFrame: Baseline, Week 24
measure: DB Period: Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24: ITT Estimand
timeFrame: Baseline, Week 24
measure: DB Period: Percent Change From Baseline in Apolipoprotein B at Week 12: ITT Estimand
timeFrame: Baseline, Week 12
measure: DB Period: Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol at Week 12: ITT Estimand
timeFrame: Baseline, Week 12
measure: DB Period: Percent Change From Baseline in Total Cholesterol at Week 12: ITT Estimand
timeFrame: Baseline, Week 12
measure: DB Period: Percentage of Participants Who Achieved Low Density Lipoprotein Cholesterol Level Lower Than (<) 130 mg/dL (3.37 mmol/L) at Week 24: ITT Estimand
timeFrame: At Week 24
measure: DB Period: Percentage of Participants Who Achieved Low Density Lipoprotein Cholesterol Level <130 mg/dL (3.37 mmol/L) at Week 12: ITT Estimand
timeFrame: At Week 12
measure: DB Period: Percentage of Participants Achieving Low Density Lipoprotein Cholesterol <110 mg/dL (2.84 mmol/L) at Week 24: ITT Estimand
timeFrame: At Week 24
measure: DB Period: Percentage of Participants Achieving Low Density Lipoprotein Cholesterol <110 mg/dL (2.84 mmol/L) at Week 12: ITT Estimand
timeFrame: At Week 12
measure: DB Period: Percent Change From Baseline in Lipoprotein (a) at Week 24: ITT Estimand
timeFrame: Baseline, Week 24
measure: DB Period: Percent Change From Baseline in Lipoprotein (a) at Week 12: ITT Estimand
timeFrame: Baseline, Week 12
measure: DB Period: Percent Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) at Week 24: ITT Estimand
timeFrame: Baseline, Week 24
measure: DB Period: Percent Change From Baseline in Fasting Triglycerides (TG) at Week 24: ITT Estimand
timeFrame: Baseline, Week 24
measure: DB Period: Percent Change From Baseline in Apolipoprotein A1 (Apo A1) at Week 24: ITT Estimand
timeFrame: Baseline, Week 24
measure: DB Period: Percent Change From Baseline in High-Density Lipoprotein Cholesterol at Week 12: ITT Estimand
timeFrame: Baseline, Week 12
measure: DB Period: Percent Change From Baseline in Fasting Triglycerides (TG) at Week 12: ITT Estimand
timeFrame: Baseline, Week 12
measure: DB Period: Percent Change From Baseline in Apolipoprotein A1 at Week 12: ITT Estimand
timeFrame: Baseline, Week 12
measure: DB Period: Percent Change From Baseline in Low Density Lipoprotein Cholesterol at Weeks 12, and 24: On-treatment Estimand
timeFrame: Baseline, Weeks 12, and 24
measure: DB Period: Percent Change From Baseline in Apolipoprotein B at Weeks 12 and 24: On-treatment Estimand
timeFrame: Baseline, Weeks 12 and 24
measure: DB Period: Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol at Weeks 12 and 24: On-treatment Estimand
timeFrame: Baseline, Weeks 12 and 24
measure: DB Period: Percent Change From Baseline in Total Cholesterol at Weeks 12 and 24: On-treatment Estimand
timeFrame: Baseline, Weeks 12 and 24
measure: DB Period: Percentage of Participants Who Achieved Low Density Lipoprotein Cholesterol < 130 mg/dL (3.37 mmol/L) at Weeks 12 and 24: On-treatment Estimand
timeFrame: Weeks 12 and 24
measure: DB Period: Percentage of Participants Who Achieved Low Density Lipoprotein Cholesterol < 110 mg/dL (2.84 mmol/L) at Weeks 12 and 24: On-treatment Estimand
timeFrame: Weeks 12 and 24
measure: DB Period: Percent Change From Baseline in Lipoprotein (a) at Weeks 12 and 24: On-treatment Estimand
timeFrame: Baseline, Weeks 12 and 24
measure: DB Period: Percent Change From Baseline in Apolipoprotein A1 at Weeks 12 and 24: On-treatment Estimand
timeFrame: Baseline, Weeks 12 and 24
measure: DB Period: Percent Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) at Weeks 12 and 24: On-treatment Estimand
timeFrame: Baseline, Weeks 12, and 24
measure: DB Period: Percent Change From Baseline in Fasting Triglycerides at Weeks 12 and 24: On-treatment Estimand
timeFrame: Baseline, Weeks 12, and 24
measure: DB Period: Absolute Change From Baseline in Apo B/Apo A-1 Ratio at Weeks 12 and 24: ITT Estimand
timeFrame: Baseline, Weeks 12, and 24
measure: DB Period: Absolute Change From Baseline in Apo B/Apo A-1 Ratio at Weeks 12 and 24: On-treatment Estimand
timeFrame: Baseline, Weeks 12, and 24
measure: DB Period: Percentage of Participants Who Achieved at Least 30 Percent (%) Reduction in Low Density Lipoprotein Cholesterol Level From Baseline at Weeks 12 and 24: ITT Estimand
timeFrame: At Weeks 12 and 24
measure: DB Period: Percentage of Participants Achieved at Least 30% Reduction in Low Density Lipoprotein Cholesterol Level From Baseline at Weeks 12 and 24: On-treatment Estimand
timeFrame: At Weeks 12 and 24
measure: DB Period: Percentage of Participants Who Achieved at Least 50% Reduction in Low Density Lipoprotein Cholesterol Level From Baseline at Weeks 12 and 24: ITT Estimand
timeFrame: At Weeks 12 and 24
measure: DB Period: Percentage of Participants Who Achieved at Least 50% Reduction in Low Density Lipoprotein Cholesterol Level From Baseline at Weeks 12 and 24: On-treatment Estimand
timeFrame: At Weeks 12 and 24
measure: DB Period: Percent Change in Low Density Lipoprotein Cholesterol From Baseline to Weeks 8, 12 and 24: ITT Estimand
timeFrame: Baseline to Weeks 8, 12 and 24
measure: DB Period: Percent Change in Low Density Lipoprotein Cholesterol From Baseline to Weeks 8, 12 and 24: On-treatment Estimand
timeFrame: Baseline to Weeks 8, 12 and 24
measure: OL Period: Percent Change in Low Density Lipoprotein Cholesterol From Baseline to Week 104: ITT Estimand
timeFrame: Baseline, Week 104
measure: OL Period: Percent Change in Low Density Lipoprotein Cholesterol From Baseline to Week 104: On-treatment Estimand
timeFrame: Baseline, Week 104
measure: Change From Baseline in Cogstate Battery Test - Overall Composite Score at Weeks 24, 68 and 104
timeFrame: Baseline, Weeks 24, 68 and 104
measure: Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104
timeFrame: Baseline, Weeks 24, 68 and 104
measure: DB Period: Number of Participants With Treatment-Emergent (TE) Positive Anti-Alirocumab Antibodies (ADA) Response
timeFrame: Up to 24 weeks
Other outcomes:
Locations:
city: Boca Raton
country: United States
facility: Excel Medical Clinical Trials, LLC-Site Number:8400001
state: Florida
city: Saint Louis
country: United States
facility: Washington University School of Medicine-Site Number:8400006
state: Missouri
city: Charlotte
country: United States
facility: Presbyterian Novant Heart & Wellness-Site Number:8400002
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center-Site Number:8400005
state: Ohio
city: Nashville
country: United States
facility: Vanderbilt University-Site Number:8400003
state: Tennessee
city: Buenos Aires
country: Argentina
facility: Investigational Site Number :0320001
city: Wien
country: Austria
facility: Investigational Site Number :0400001
city: Porto Alegre
country: Brazil
facility: Investigational Site Number :0760004
state: Rio Grande Do Sul
city: Sao Paulo
country: Brazil
facility: Investigational Site Number :0760001
city: Plovdiv
country: Bulgaria
facility: Investigational Site Number :1000002
city: Quebec
country: Canada
facility: Investigational Site Number :1240001
city: Brno
country: Czechia
facility: Investigational Site Number :2030002
city: Praha 5 - Motol
country: Czechia
facility: Investigational Site Number :2030001
city: Copenhagen
country: Denmark
facility: Investigational Site Number :2080001
city: HUS
country: Finland
facility: Investigational Site Number :2460001
city: Bron
country: France
facility: Investigational Site Number :2500001
city: Nantes
country: France
facility: Investigational Site Number :2500002
city: Budapest
country: Hungary
facility: Investigational Site Number :3480001
city: Milano
country: Italy
facility: Investigational Site Number :3800003
city: Palermo
country: Italy
facility: Investigational Site Number :3800001
city: Roma
country: Italy
facility: Investigational Site Number :3800002
city: Beirut
country: Lebanon
facility: Investigational Site Number :4220001
city: Room Hospital Street, Achrafie
country: Lebanon
facility: Investigational Site Number :4220003
city: Guadalajara
country: Mexico
facility: Investigational Site Number :4840008
state: Jalisco
city: Oaxaca
country: Mexico
facility: Investigational Site Number :4840007
city: Amsterdam
country: Netherlands
facility: Investigational Site Number :5280001
city: Oslo
country: Norway
facility: Investigational Site Number :5780001
city: Gdansk
country: Poland
facility: Investigational Site Number :6160002
state: Pomorskie
city: Lodz
country: Poland
facility: Investigational Site Number :6160001
city: Kazan
country: Russian Federation
facility: Investigational Site Number :6430006
city: Kemerovo
country: Russian Federation
facility: Investigational Site Number :6430001
city: Moscow
country: Russian Federation
facility: Investigational Site Number :6430004
city: Ufa
country: Russian Federation
facility: Investigational Site Number :6430002
city: Ljubljana
country: Slovenia
facility: Investigational Site Number :7050001
city: Parow
country: South Africa
facility: Investigational Site Number :7100002
city: Pamplona
country: Spain
facility: Investigational Site Number :7240003
state: Navarra
city: A Coruña
country: Spain
facility: Investigational Site Number :7240002
city: Badalona
country: Spain
facility: Investigational Site Number :7240004
city: Barcelona
country: Spain
facility: Investigational Site Number :7240001
city: Stockholm
country: Sweden
facility: Investigational Site Number :7520001
city: Taipei
country: Taiwan
facility: Investigational Site Number :1580001
city: Ankara
country: Turkey
facility: Investigational Site Number :7920002
city: Izmir
country: Turkey
facility: Investigational Site Number :7920001
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: