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

NCT03510715 | Completed Phase 3 Results DMC FDA Drug

• 3 other identifiers: EFC146602017-002297-39U1111-1200-2046
• Study Type: interventional
• Target: 18
• Locations: 10 countries
• Sites: 10

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.

Conditions

Hypercholesterolemia

Keywords

Pediatrics, Homozygous Familial Hypercholesterolemia, Alirocumab, PCSK9 inhibitor, Low-density Lipoprotein Cholesterol (LDL-C)

Outcome Measures

Primary Outcomes (1)

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

  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).

  Baseline to Week 12

Secondary Outcomes (12)

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

  Baseline to Week 12

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

  Baseline to Weeks 24 and 48

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

  Baseline to Weeks 12, 24 and 48

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

  Baseline to Weeks 12, 24 and 48

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

  Baseline to Weeks 12, 24 and 48

Study Arms (1)

Alirocumab

EXPERIMENTAL

Participants with BW less than (\<) 50 kilograms (kg) received subcutaneous (SC) injection of alirocumab 75 mg Q2W for 48 weeks. Alirocumab dose was up-titrated to 150 mg Q2W from Week 12 in case of increase in BW with BW greater than or equal to \[\>=\] 50 kg. Participants with BW \>=50 kg received SC injection of alirocumab 150 mg Q2W for 48 weeks.

Drug: Alirocumab SAR236553 (REGN727); Drug: Atorvastatin; Drug: Simvastatin; Drug: Fluvastatin; Drug: Pravastatin; Drug: Lovastatin; Drug: Rosuvastatin; Drug: Ezetimibe; Drug: Cholestyramine; Drug: Nicotinic acid; Drug: Fenofibrate; Drug: Omega-3 fatty acids

Interventions

Alirocumab SAR236553 (REGN727) DRUG

Pharmaceutical form: solution for injection in pre-filled syringe, Route of administration: subcutaneous (SC)

Alirocumab

Atorvastatin DRUG

Pharmaceutical form: tablet, Route of administration: oral

Alirocumab

Simvastatin DRUG

Pharmaceutical form: tablet, Route of administration: oral

Alirocumab

Fluvastatin DRUG

Pharmaceutical form: capsule, Route of administration: oral

Alirocumab

Pravastatin DRUG

Pharmaceutical form: tablet, Route of administration: oral

Alirocumab

Lovastatin DRUG

Pharmaceutical form: tablet, Route of administration: oral

Alirocumab

Rosuvastatin DRUG

Pharmaceutical form: tablet, Route of administration: oral

Alirocumab

Ezetimibe DRUG

Pharmaceutical form: tablet, Route of administration: oral

Alirocumab

Cholestyramine DRUG

Pharmaceutical form: oral suspension, Route of administration: oral

Alirocumab

Nicotinic acid DRUG

Pharmaceutical form: tablet, Route of administration: oral

Alirocumab

Fenofibrate DRUG

Pharmaceutical form: tablet, Route of administration: oral

Alirocumab

Omega-3 fatty acids DRUG

Pharmaceutical form: capsule, Route of administration: oral

Alirocumab

Eligibility Criteria

• Age: 8 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sanofi: lead
• Regeneron Pharmaceuticals: collaborator

Study Sites (10)

Investigational Site Number 0760001

São Paulo, 05403-000, Brazil

Location

Investigational Site Number 1240001

Québec, G1V 4W2, Canada

Location

Investigational Site Number 2080001

Viborg, 8800, Denmark

Location

Investigational Site Number 4840006

Oaxaca City, 68000, Mexico

Location

Investigational Site Number 5280001

Amsterdam, 1105AZ, Netherlands

Location

Investigational Site Number 6430002

Kemerovo, 650002, Russia

Location

Investigational Site Number 7050001

Ljubljana, 1000, Slovenia

Location

Investigational Site Number 7240001

A Coruña, 15001, Spain

Location

Investigational Site Number 1580001

Taipei, 112, Taiwan

Location

Investigational Site Number 7920001

Izmir, 35040, Turkey (Türkiye)

Location

Related Publications (1)

• 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.

  PMID: 36325897 DERIVED

MeSH Terms

Conditions

Hypercholesterolemia; Homozygous Familial Hypercholesterolemia

Interventions

alirocumab; Atorvastatin; Simvastatin; Fluvastatin; Pravastatin; Lovastatin; Rosuvastatin Calcium; Ezetimibe; Cholestyramine Resin; Niacin; Fenofibrate; Fatty Acids, Omega-3

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Sulfonamides; Amides; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Sulfones; Sulfur Compounds; Pyrimidines; Azetidines; Azetines; Polystyrenes; Plastics; Polymers; Macromolecular Substances; Biomedical and Dental Materials; Manufactured Materials; Technology, Industry, and Agriculture; Nicotinic Acids; Acids, Heterocyclic; Pyridines; Fibric Acids; Isobutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Phenyl Ethers; Ethers; Benzophenones; Benzene Derivatives; Phenols; Ketones; Dietary Fats, Unsaturated; Dietary Fats; Fats; Fatty Acids, Unsaturated; Fish Oils; Oils

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi

Contact-US@sanofi.com

800-633-1610

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 18, 2018
• First Posted: April 27, 2018
• Study Start: August 31, 2018
• Primary Completion: February 17, 2020
• Study Completion: February 17, 2020
• Last Updated: December 29, 2020
• Results First Posted: December 29, 2020

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will not share

Locations

ME (1); TW (1); SL (1); DK (1); ES (1); TU (1); BR (1); CA (1); NL (1); RU (1)