NCT03510884|CompletedPhase 3ResultsDMCFDA Drug

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

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

Sanofi ClinicalTrials.gov

Compare

3 other identifiers

EFC146432017-001903-60U1111-1193-0721

Study Type

interventional

Target

153

Locations

24 countries

Sites

Timeline

RegisteredApr 2018

StartedMay 2018

CompletionAug 2022

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.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

153

participants targeted

Target at P25-P50 for phase_3

Timeline

Completed

Started May 2018

Typical duration for phase_3

Geographic Reach

24 countries

43 active sites

Status

completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

4.2 years study duration

First Submitted

Initial submission to the registry

April 18, 2018

Completed

9 days until next milestone

First Posted

Study publicly available on registry

April 27, 2018

Completed

1 month until next milestone

Study Start

First participant enrolled

May 31, 2018

Completed

2.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 14, 2021

Completed

1.6 years until next milestone

Study Completion

Last participant's last visit for all outcomes

August 5, 2022

Completed

9 months until next milestone

Results Posted

Study results publicly available

May 6, 2023

Completed

Last Updated

May 6, 2023

Status Verified

April 1, 2023

Enrollment Period

2.6 years

First QC Date

April 18, 2018

Results QC Date

January 9, 2023

Last Update Submit

April 12, 2023

Conditions

Hypercholesterolaemia

Outcome Measures

Primary Outcomes (1)

DB Period: Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 24: Intent-to-treat (ITT) Estimand
Adjusted least square (LS) means and standard errors (SE) were obtained from mixed-effect model with repeated measures (MMRM) model. All post-baseline data available up to Week 24 were used and missing data were accounted for by the MMRM model. MMRM model was run on participants with a Baseline value and a post-baseline value for at least one timepoint used in the model.
Baseline, Week 24

Secondary Outcomes (42)

DB Period: Percent Change From Baseline in Low Density Lipoprotein Cholesterol at Week 12: ITT Estimand
Baseline, Week 12
DB Period: Percent Change From Baseline in Apolipoprotein B (Apo B) at Week 24: ITT Estimand
Baseline, Week 24
DB Period: Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 24: ITT Estimand
Baseline, Week 24
DB Period: Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24: ITT Estimand
Baseline, Week 24
DB Period: Percent Change From Baseline in Apolipoprotein B at Week 12: ITT Estimand
Baseline, Week 12
+37 more secondary outcomes

Study Arms (4)

Placebo/Alirocumab Q2W

EXPERIMENTAL

Participants received subcutaneous (SC) injection of placebo (matched to alirocumab) based on their body weight (BW) (less than \[\<\] 50 kilograms \[kg\] or greater than or equal to \[\>=\] 50 kg) Q2W for 24 weeks in DB treatment period added to stable LMT. After completion of DB treatment period, eligible participants entered into OL treatment period and received alirocumab 40 milligrams (mg) (for BW \<50 kg) or 75 mg (for BW \>=50 kg) Q2W from Week 24 up to an additional 80 weeks (i.e., up to Week 104) added to stable LMT. After Week 24, dose up-titrated from 40 mg to 75 mg when BW increased from \<50 kg to \>=50 kg. From Week 32 up to Week 104, based on participant LDL-C value, alirocumab dose was either up-titrated as 40 mg to 75 mg (for BW \<50 kg) or 75 mg to 150 mg (for BW \>=50 kg) or down titrated as 75 mg to 40 mg (for BW \<50 kg) or 150 mg to 75 mg (for BW \>=50 kg).

Drug: Alirocumab SAR236553 (REGN727)Drug: RosuvastatinDrug: AtorvastatinDrug: SimvastatinDrug: PravastatinDrug: LovastatinDrug: FluvastatinDrug: EzetimibeDrug: CholestyramineDrug: Nicotinic acidDrug: FenofibrateDrug: Omega-3 fatty acidsDrug: Placebo

Alirocumab Q2W

EXPERIMENTAL

Participants received SC injection of alirocumab 40 mg (for BW \<50 kg) or 75 mg (for BW \>=50 kg) Q2W for 24 weeks in DB treatment period added to stable LMT. Alirocumab dose was up-titrated to 75 mg or 150 mg Q2W from Week 12, when LDL-C level was \>=110 milligrams per deciliter (mg/dL) (2.85 millimoles per liter \[mmol/L\]) at Week 8. After completion of DB treatment period, eligible participants entered into OL treatment period and received alirocumab 40 mg (for BW \<50 kg) or 75 mg (for BW \>=50 kg) from Week 24 up to an additional 80 weeks (i.e., up to Week 104) added to stable LMT. After Week 24, dose up-titrated from 40 mg to 75 mg when BW increased from \<50 kg to \>=50 kg. From Week 32 up to Week 104, based on participant LDL-C value, alirocumab dose was either up-titrated as 40 mg to 75 mg (for BW \<50 kg) or 75 mg to 150 mg (for BW \>=50 kg) or down titrated as 75 mg to 40 mg (for BW \<50 kg) or 150 mg to 75 mg (for BW \>=50 kg).

Placebo/Alirocumab Q4W

EXPERIMENTAL

Participants received SC injection of placebo (matched to alirocumab) based on their BW (\<50 kg or \>=50 kg) Q4W for 24 weeks in DB treatment period added to stable LMT. After completion of DB treatment period, eligible participants entered into OL treatment period and received alirocumab 150 mg (for BW \<50 kg) or 300 mg (for BW \>=50 kg) Q4W from Week 24 up to an additional 80 weeks (i.e., up to Week 104) added to stable LMT. After Week 24, dose up-titrated from 150 mg to 300 mg when BW increased from \<50 kg to \>=50 kg. From Week 32 up to Week 104, based on participant LDL-C value, alirocumab dose was either up-titrated as 150 mg Q4W to 75 mg Q2W (for BW \<50 kg) or 300 mg Q4W to 150 mg Q2W (for BW \>=50 kg) or down titrated as 75 mg Q2W to 40 mg Q2W (for BW \<50 kg) or 150 mg Q2W to 75 mg Q2W (for BW \>=50 kg).

Alirocumab Q4W

EXPERIMENTAL

Participants received SC injection of alirocumab 150 mg (for BW \<50 kg) or 300 mg (for BW \>=50 kg) Q4W for 24 weeks in DB treatment period added to stable LMT. Alirocumab dose was up-titrated to 75 mg or 150 mg Q2W from Week 12, when LDL-C level \>=110 mg/dL (2.85 mmol/L) at Week 8. After completion of DB treatment period, eligible participants entered into OL treatment period and received alirocumab 150 mg (for BW \<50 kg) or 300 mg (for BW \>=50 kg) from Week 24 up to an additional 80 weeks (i.e., up to Week 104) added to stable LMT. After Week 24, dose up-titrated from 150 mg to 300 mg when BW increased from \<50 kg to \>=50 kg. From Week 32 up to Week 104, based on participant LDL-C value, alirocumab dose was either up-titrated as 150 mg Q4W to 75 mg Q2W (for BW \<50 kg) or 300 mg Q4W to 150 mg Q2W (for BW \>=50 kg) or down titrated as 75 mg Q2W to 40 mg Q2W (for BW \<50 kg) or 150 mg Q2W to 75 mg Q2W (for BW \>=50 kg).