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

Sponsor
Sanofi (Industry)
Overall Status
Completed
CT.gov ID
NCT03510884
Collaborator
Regeneron Pharmaceuticals (Industry)
153
Enrollment
43
Locations
2
Arms
50.2
Actual Duration (Months)
3.6
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

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 patients 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 Objective:

  • To evaluate the efficacy of alirocumab versus placebo on low-density lipoprotein cholesterol (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.

Condition or Disease Intervention/Treatment Phase
Phase 3

Detailed Description

The study duration is 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 treatment period: 80 weeks).

Study Design

Study Type:
Interventional
Actual Enrollment :
153 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Care Provider, Investigator)
Primary Purpose:
Treatment
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
Actual Study Start Date :
May 31, 2018
Actual Primary Completion Date :
Jan 14, 2021
Actual Study Completion Date :
Aug 5, 2022

Arms and Interventions

Arm Intervention/Treatment
Experimental: Alirocumab

Alirocumab (one of 4 doses, depending on body weight and Q2W or Q4W dose regimens) will be administered subcutaneously (SC). Patients treated with optimal dose of statin with or without other LMT or non-statin LMT if statin intolerant at stable dose.

Drug: Alirocumab SAR236553 (REGN727)
Pharmaceutical form:solution Route of administration: subcutaneous injection
Other Names:
  • Praluent

    • Drug: Rosuvastatin
    Pharmaceutical form:tablet Route of administration: oral

    Drug: Atorvastatin
    Pharmaceutical form:Tablet Route of administration: Oral

    Drug: Simvastatin
    Pharmaceutical form:Tablet Route of administration: Oral

    Drug: Pravastatin
    Pharmaceutical form:Tablet Route of administration: Oral

    Drug: Lovastatin
    Pharmaceutical form:Tablet Route of administration: Oral

    Drug: Fluvastatin
    Pharmaceutical form:Capsule Route of administration: Oral

    Drug: Ezetimibe
    Pharmaceutical form:Tablet Route of administration: Oral

    Drug: Cholestyramine
    Pharmaceutical form:oral suspension Route of administration: oral

    Drug: Nicotinic acid
    Pharmaceutical form:Tablet Route of administration: Oral

    Drug: Fenofibrate
    Pharmaceutical form:Tablet Route of administration: Oral

    Drug: Omega-3 fatty acids
    Pharmaceutical form:capsule Route of administration: oral
    Placebo Comparator: Placebo

    Alirocumab Placebo will be administered SC. Patients treated with optimal dose of statin with or without other LMT or non-statin LMT if statin intolerant at stable dose.

    Drug: Rosuvastatin
    Pharmaceutical form:tablet Route of administration: oral

    Drug: Atorvastatin
    Pharmaceutical form:Tablet Route of administration: Oral

    Drug: Simvastatin
    Pharmaceutical form:Tablet Route of administration: Oral

    Drug: Pravastatin
    Pharmaceutical form:Tablet Route of administration: Oral

    Drug: Lovastatin
    Pharmaceutical form:Tablet Route of administration: Oral

    Drug: Fluvastatin
    Pharmaceutical form:Capsule Route of administration: Oral

    Drug: Ezetimibe
    Pharmaceutical form:Tablet Route of administration: Oral

    Drug: Cholestyramine
    Pharmaceutical form:oral suspension Route of administration: oral

    Drug: Nicotinic acid
    Pharmaceutical form:Tablet Route of administration: Oral

    Drug: Fenofibrate
    Pharmaceutical form:Tablet Route of administration: Oral

    Drug: Omega-3 fatty acids
    Pharmaceutical form:capsule Route of administration: oral

    Drug: Placebo
    Pharmaceutical form:solution Route of administration: subcutaneous injection

    Outcome Measures

    Primary Outcome Measures

    1. Percent change in low-density lipoprotein cholesterol (LDL-C) [From baseline to Week 24]

      Percent change in LDL-C from baseline to Week 24

    Secondary Outcome Measures

    1. Percent change in LDL-C [From baseline to Week 12]

      Percent change in LDL-C from baseline to Week 12

    2. Percent change in Apo B [From baseline to Week 12 and to Week 24]

      Percent change in Apo B from baseline to Week 12 and to Week 24

    3. Percent change in non-high density lipoprotein cholesterol (non HDL-C) [From baseline to Week 12 and to Week 24]

      Percent change in non-HDL-C from baseline to Week 12 and to Week 24

    4. Percent change in Total-C [From baseline to Week 12 and to Week 24]

      Percent change in Total-C from baseline to Week 12 and to Week 24

    5. Patients with LDL-C level <130 mg/dL (3.37 mmol/L) [From baseline to Week 12 and to Week 24]

      Proportion of patients with LDL-C level < 130 mg/dL (3.37 mmol/L) at Week 12 and at Week 24

    6. Patients with LDL-C level <110 mg/dL (2.84 mmol/L) [From baseline to Week 12 and to Week 24]

      Proportion of patients with LDL-C level < 110 mg/dL (2.84 mmol/L) at Week 12 and at Week 24

    7. Percent change in Lp(a) [From baseline to Week 12 and to Week 24]

      Percent change in lipoprotein (a) from baseline to Week 12 and to Week 24

    8. Percent change in HDL-C [From baseline to Week 12 and to Week 24]

      Percent change in HDL-C from baseline to Week 12 and to Week 24

    9. Percent change in TG [From baseline to Week 12 and to Week 24]

      Percent change in fasting triglycerides (TG) from baseline to Week 12 and to Week 24

    10. Percent change in Apo A-1 [From baseline to Week 12 and to Week 24]

      Percent change in apolipoprotein A1 (Apo A-1) from baseline to Week 12 and to Week 24

    11. Number of patients with adverse events [Up to Week 104]

      Number of patients with adverse events

    12. Cogstate battery test [At Day 1, Weeks 24, 68, and 104]

      The Cogstate battery test will assess maturing cognition across a broad number of key developmental functions

    13. Tanner stage [At Weeks 24, 44, 68, and 104]

      The Tanner stages will be measured to assess stages of pubertal development -

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    8 Years to 17 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion criteria:

    • Children and adolescent male and female Patients aged 8 to 17 years at the time of signed informed consent.

    • Patients with diagnosis of heterozygous familial hypercholesterolemia (heFH) through genotyping or clinical criteria.

    • Patients 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.

    • Patients with calculated LDL-C greater than or equal to 130 mg/dL (≥3.37 mmol/L) at the screening visit except for Patients who have previously participated in the DFI14223 study.

    • A signed informed consent indicating parental permission with or without patient assent.

    Exclusion criteria:

    • Patient with body weight less than 25 kilograms.

    • Patients aged of 8 to 9 years not at Tanner stage 1 and patients aged of 10 to 17 years not at least at Tanner stage 2 in their development.

    • Patients with secondary hyperlipidemia.

    • Diagnosis of homozygous familial hypercholesterolemia.

    • Patient who has received lipid apheresis treatment within 2 months prior to the screening period, or has plans to receive it during the study.

    • Patients with uncontrolled type 1 or type 2 diabetes mellitus.

    • Patients with known uncontrolled thyroid disease.

    • Patients with uncontrolled hypertension.

    • Fasting triglycerides >350 mg/dL (3.95 mmol/L).

    • Severe renal impairment (ie, 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 patient's potential participation in a clinical trial.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Excel Medical Clinical Trials, LLC-Site Number:8400001 Boca Raton Florida United States 33434
    2 Washington University School of Medicine-Site Number:8400006 Saint Louis Missouri United States 63110
    3 Presbyterian Novant Heart & Wellness-Site Number:8400002 Charlotte North Carolina United States 28204
    4 Cincinnati Children's Hospital Medical Center-Site Number:8400005 Cincinnati Ohio United States 45229
    5 Vanderbilt University-Site Number:8400003 Nashville Tennessee United States 37232
    6 Investigational Site Number :0320001 Buenos Aires Argentina C1245AAM
    7 Investigational Site Number :0400001 Wien Austria 1090
    8 Investigational Site Number :0760004 Porto Alegre Rio Grande Do Sul Brazil 91350-200
    9 Investigational Site Number :0760001 Sao Paulo Brazil 05403-900
    10 Investigational Site Number :1000002 Plovdiv Bulgaria 4002
    11 Investigational Site Number :1240001 Quebec Canada G1V 4W2
    12 Investigational Site Number :2030002 Brno Czechia 62500
    13 Investigational Site Number :2030001 Praha 5 - Motol Czechia 15006
    14 Investigational Site Number :2080001 Copenhagen Denmark 2100
    15 Investigational Site Number :2460001 HUS Finland 00029
    16 Investigational Site Number :2500001 Bron France 69500
    17 Investigational Site Number :2500002 Nantes France 44093
    18 Investigational Site Number :3480001 Budapest Hungary 1094
    19 Investigational Site Number :3800003 Milano Italy 20142
    20 Investigational Site Number :3800001 Palermo Italy 90127
    21 Investigational Site Number :3800002 Roma Italy
    22 Investigational Site Number :4220001 Beirut Lebanon
    23 Investigational Site Number :4220003 Room Hospital Street, Achrafie Lebanon 00000
    24 Investigational Site Number :4840008 Guadalajara Jalisco Mexico 44100
    25 Investigational Site Number :4840007 Oaxaca Mexico 68000
    26 Investigational Site Number :5280001 Amsterdam Netherlands 1105AZ
    27 Investigational Site Number :5780001 Oslo Norway
    28 Investigational Site Number :6160002 Gdansk Pomorskie Poland
    29 Investigational Site Number :6160001 Lodz Poland 93-338
    30 Investigational Site Number :6430006 Kazan Russian Federation 420138
    31 Investigational Site Number :6430001 Kemerovo Russian Federation 650002
    32 Investigational Site Number :6430004 Moscow Russian Federation 115446
    33 Investigational Site Number :6430002 Ufa Russian Federation 450083
    34 Investigational Site Number :7050001 Ljubljana Slovenia 1000
    35 Investigational Site Number :7100002 Parow South Africa 7500
    36 Investigational Site Number :7240003 Pamplona Navarra Spain 31008
    37 Investigational Site Number :7240002 A Coruna Spain 15001
    38 Investigational Site Number :7240004 Badalona Spain 08916
    39 Investigational Site Number :7240001 Barcelona Spain 08208
    40 Investigational Site Number :7520001 Stockholm Sweden 171 76
    41 Investigational Site Number :1580001 Taipei Taiwan 112
    42 Investigational Site Number :7920002 Ankara Turkey 06500
    43 Investigational Site Number :7920001 Izmir Turkey 35040

    Sponsors and Collaborators

    • Sanofi
    • Regeneron Pharmaceuticals

    Investigators

    • Study Director: Clinical Sciences & Operations, Sanofi

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Sanofi
    ClinicalTrials.gov Identifier:
    NCT03510884
    Other Study ID Numbers:
    • EFC14643
    • 2017-001903-60
    • U1111-1193-0721
    First Posted:
    Apr 27, 2018
    Last Update Posted:
    Aug 19, 2022
    Last Verified:
    Aug 17, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Hyperlipoproteinemia Type II
    Hypercholesterolemia
    Nicotinic Acids
    Niacin
    Niacinamide
    Atorvastatin
    Rosuvastatin Calcium
    Simvastatin
    Ezetimibe
    Pravastatin
    Lovastatin
    Cholestyramine Resin
    Fenofibrate

    Study Results

    No Results Posted as of Aug 19, 2022