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Completed

NCT Number: NCT03510715

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

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.

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Key information

Conditions

Hypercholesterolemia Congenital, Hereditary, and Neonatal Diseases and Abnormalities Dyslipidemias Genetic Diseases, Inborn Homozygous Familial Hypercholesterolemia Hyperlipidemias Hyperlipoproteinemia Type II Hyperlipoproteinemias Lipid Metabolism Disorders Lipid Metabolism, Inborn Errors Metabolic Diseases Metabolism, Inborn Errors Nutritional and Metabolic Diseases

Age range

8 year–17 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Investigational Site Number 0760001, São Paulo, Brazil

Loading trial locations.

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

alirocumab SAR236553 (REGN727)

Drug

Pharmaceutical form: solution for injection in pre-filled syringe,

Route of administration: subcutaneous (SC)

atorvastatin

Drug

Pharmaceutical form: tablet,

Route of administration: oral

simvastatin

Drug

Pharmaceutical form: tablet,

Route of administration: oral

Fluvastatin

Drug

Pharmaceutical form: capsule,

Route of administration: oral

Pravastatin

Drug

Pharmaceutical form: tablet,

Route of administration: oral

lovastatin

Drug

Pharmaceutical form: tablet,

Route of administration: oral

Rosuvastatin

Drug

Pharmaceutical form: tablet,

Route of administration: oral

ezetimibe

Drug

Pharmaceutical form: tablet,

Route of administration: oral

Cholestyramine

Drug

Pharmaceutical form: oral suspension,

Route of administration: oral

Nicotinic acid

Drug

Pharmaceutical form: tablet,

Route of administration: oral

fenofibrate

Drug

Pharmaceutical form: tablet,

Route of administration: oral

Omega-3 Fatty acids

Drug

Pharmaceutical form: capsule,

Route of administration: oral

Primary outcomes

  1. Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12: Intent-to-Treat (ITT) Analysis

    Time frame: Baseline to Week 12

    Adjusted least square (LS) means and standard errors were obtained from the mixed model analysis with repeated measures (MMRM) to account for missing data using all available post-baseline data from Week 4 to Week 48 regardless of status on- or off-treatment used in the model (ITT analysis).

Secondary outcomes

  1. Percent Change From Baseline in Low-Density Lipoprotein Cholesterol at Week 12: On-treatment Analysis

    Time frame: Baseline to Week 12

    Adjusted LS means and standard errors were obtained from the MMRM model to account for missing data using all available post-baseline on-treatment data from Week 4 to Week 48 (on-treatment Analysis).

  2. Percent Change From Baseline in Low-Density Lipoprotein Cholesterol at Weeks 24 and 48: ITT Analysis/On-treatment Analysis

    Time frame: Baseline to Weeks 24 and 48

    Adjusted LS means and standard errors were obtained from the MMRM model to account for missing data using all available post-baseline data from Week 4 to Week 48 regardless of status on- or off-treatment used in the model (ITT analysis). Although separate analyses of all available data (ITT analysis) and only data collected within a defined time window (On-treatment analysis) were planned, if all values used in the ITT approach were within the on-treatment time window, the on-treatment analysis would be identical to the ITT analysis, thus the results would be identical and a single outcome measure presenting the results for both types of analysis would be provided.

  3. Percent Change From Baseline in Apolipoprotein (Apo) B at Weeks 12, 24 and 48: ITT Analysis/On-treatment Analysis

    Time frame: Baseline to Weeks 12, 24 and 48

    Adjusted LS means and standard errors were obtained from the MMRM model to account for missing data using all available post-baseline data from Week 4 to Week 48 regardless of status on- or off-treatment used in the model (ITT analysis). Although separate analyses of all available data (ITT analysis) and only data collected within a defined time window (On-treatment analysis) were planned, if all values used in the ITT approach were within the on-treatment time window, the on-treatment analysis would be identical to the ITT analysis, thus the results would be identical and a single outcome measure presenting the results for both types of analysis would be provided.

  4. Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Weeks 12, 24 and 48 - ITT Analysis/On-treatment Analysis

    Time frame: Baseline to Weeks 12, 24 and 48

    Adjusted LS means and standard errors were obtained from the MMRM model to account for missing data using all available post-baseline data from Week 4 to Week 48 regardless of status on- or off-treatment used in the model (ITT analysis). Although separate analyses of all available data (ITT analysis) and only data collected within a defined time window (On-treatment analysis) were planned, if all values used in the ITT approach were within the on-treatment time window, the on-treatment analysis would be identical to the ITT analysis, thus the results would be identical and a single outcome measure presenting the results for both types of analysis would be provided.

  5. Percent Change From Baseline in Total Cholesterol (Total-C) at Weeks 12, 24 and 48: ITT Analysis/On-treatment Analysis

    Time frame: Baseline to Weeks 12, 24 and 48

    Adjusted LS means and standard errors were obtained from the MMRM model to account for missing data using all available post-baseline data from Weeks 4 to Week 48 regardless of status on- or off-treatment used in the model (ITT analysis). Although separate analyses of all available data (ITT analysis) and only data collected within a defined time window (On-treatment analysis) were planned, if all values used in the ITT approach were within the on-treatment time window, the on-treatment analysis would be identical to the ITT analysis, thus the results would be identical and a single outcome measure presenting the results for both types of analysis would be provided.

  6. Percent Change From Baseline in Lipoprotein a (Lp) (a) at Weeks 12, 24 and 48: ITT Analysis/On-treatment Analysis

    Time frame: Baseline to Weeks 12, 24 and 48

    Adjusted means and standard errors were obtained from a multiple imputation approach followed by a robust regression model including all available post-baseline data from Week 4 to Week 48 regardless of status on-or off-treatment used in the model (ITT analysis). Although separate analyses of all available data (ITT analysis) and only data collected within a defined time window (On-treatment analysis) were planned, if all values used in the ITT approach were within the on-treatment time window, the on-treatment analysis would be identical to the ITT analysis, thus the results would be identical and a single outcome measure presenting the results for both types of analysis would be provided.

  7. Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at Weeks 12, 24 and 48: ITT Analysis/On-treatment Analysis

    Time frame: Baseline to Weeks 12, 24 and 48

    Adjusted LS means and standard errors were obtained from the MMRM model to account for missing data using all available post-baseline data from Weeks 4 to Week 48 regardless of status on- or off-treatment used in the model (ITT analysis). Although separate analyses of all available data (ITT analysis) and only data collected within a defined time window (On-treatment analysis) were planned, if all values used in the ITT approach were within the on-treatment time window, the on-treatment analysis would be identical to the ITT analysis, thus the results would be identical and a single outcome measure presenting the results for both types of analysis would be provided.

  8. Percent Change From Baseline in Fasting Triglycerides (TG) at Weeks 12, 24 and 48: ITT Analysis/On-treatment Analysis

    Time frame: Baseline to Weeks 12, 24 and 48

    Adjusted means and standard errors were obtained from a multiple imputation approach followed by a robust regression model including all available post-baseline data from Week 4 to Week 48 regardless of status on- or off-treatment used in the model (ITT analysis). Although separate analyses of all available data (ITT analysis) and only data collected within a defined time window (On-treatment analysis) were planned, if all values used in the ITT approach were within the on-treatment time window, the on-treatment analysis would be identical to the ITT analysis, thus the results would be identical and a single outcome measure presenting the results for both types of analysis would be provided.

  9. Percent Change From Baseline in Apolipoprotein A1 (Apo A1) at Weeks 12, 24 and 48: ITT Analysis/On-treatment Analysis

    Time frame: Baseline to Weeks 12, 24 and 48

    Adjusted LS means and standard errors were obtained from the MMRM model to account for missing data using all available post-baseline data from Week 4 to 48 regardless of status on- or off-treatment used in the model (ITT analysis). Although separate analyses of all available data (ITT analysis) and only data collected within a defined time window (On-treatment analysis) were planned, if all values used in the ITT approach were within the on-treatment time window, the on-treatment analysis would be identical to the ITT analysis, thus the results would be identical and a single outcome measure presenting the results for both types of analysis would be provided.

  10. Percentage of Participants Reporting >=15 Percent (%) Reduction in LDL-C Level at Weeks 12, 24 and 48: ITT Analysis/On-treatment Analysis

    Time frame: Baseline to Weeks 12, 24 and 48

    Adjusted Percentage were obtained from a multiple imputation approach for handling of missing data including all available post-baseline data from Week 4 to Week 48 regardless of status on- or off-treatment used in the model (ITT analysis). Although separate analyses of all available data (ITT analysis) and only data collected within a defined time window (On-treatment analysis) were planned, if all values used in the ITT approach were within the on-treatment time window, the on-treatment analysis would be identical to the ITT analysis, thus the results would be identical and a single outcome measure presenting the results for both types of analysis would be provided.

  11. Absolute Change From Baseline in LDL-C Level at Weeks 12, 24 and 48: ITT Analysis/On-treatment Analysis

    Time frame: Baseline to Weeks 12, 24 and 48

    Adjusted LS means and standard errors were obtained from the MMRM model to account for missing data using all available post-baseline data from Week 4 to Week 48 regardless of status on- or off-treatment used in the model (ITT analysis). Although separate analyses of all available data (ITT analysis) and only data collected within a defined time window (On-treatment analysis) were planned, if all values used in the ITT approach were within the on-treatment time window, the on-treatment analysis would be identical to the ITT analysis, thus the results would be identical and a single outcome measure presenting the results for both types of analysis would be provided.

  12. Number of Participants With Tanner Staging at Baseline, Weeks 12, 24 and 48

    Time frame: Baseline, Weeks 12, 24 and 48

    Tanner stage defines physical measurements of development in children and adolescent based on external primary and secondary sex characteristics. Participants were evaluated for pubic hair distribution, breast development (only females) and genital development (only males), and classified in 3 categories as: Prepubescent (defined as a person just before start of the development of adult sexual characteristics), Pubescent (defined as a person at or approaching the age of puberty), Postpubescent (sexually mature or a person who has completed puberty).

Sponsors and collaborators

Lead sponsor

Sanofi

Industry

Collaborators

  • Regeneron Pharmaceuticals

Registry information

Official study title

An Open-Label Study to Evaluate the Efficacy and Safety of Alirocumab in Children and Adolescents With Homozygous Familial Hypercholesterolemia

Important dates

Study start
2018
Primary completion
2020
Study completion
2020
First posted
Apr 27, 2018
Registry last updated
Dec 29, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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