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

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ClinicalTrials.gov Identifier: NCT03510884
Recruitment Status : Recruiting
First Posted : April 27, 2018
Last Update Posted : November 19, 2019
Sponsor:
Collaborator:
Regeneron Pharmaceuticals
Information provided by (Responsible Party):
Sanofi

Tracking Information
First Submitted Date  ICMJE April 18, 2018
First Posted Date  ICMJE April 27, 2018
Last Update Posted Date November 19, 2019
Actual Study Start Date  ICMJE May 31, 2018
Estimated Primary Completion Date February 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 18, 2018)
Percent change in low-density lipoprotein cholesterol (LDL-C) [ Time Frame: From baseline to Week 24 ]
Percent change in LDL-C from baseline to Week 24
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03510884 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 18, 2018)
  • Percent change in LDL-C [ Time Frame: From baseline to Week 12 ]
    Percent change in LDL-C from baseline to Week 12
  • Percent change in Apo B [ Time Frame: From baseline to Week 12 and to Week 24 ]
    Percent change in Apo B from baseline to Week 12 and to Week 24
  • Percent change in non-high density lipoprotein cholesterol (non HDL-C) [ Time Frame: From baseline to Week 12 and to Week 24 ]
    Percent change in non-HDL-C from baseline to Week 12 and to Week 24
  • Percent change in Total-C [ Time Frame: From baseline to Week 12 and to Week 24 ]
    Percent change in Total-C from baseline to Week 12 and to Week 24
  • Patients with LDL-C level <130 mg/dL (3.37 mmol/L) [ Time Frame: 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
  • Patients with LDL-C level <110 mg/dL (2.84 mmol/L) [ Time Frame: 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
  • Percent change in Lp(a) [ Time Frame: From baseline to Week 12 and to Week 24 ]
    Percent change in lipoprotein (a) from baseline to Week 12 and to Week 24
  • Percent change in HDL-C [ Time Frame: From baseline to Week 12 and to Week 24 ]
    Percent change in HDL-C from baseline to Week 12 and to Week 24
  • Percent change in TG [ Time Frame: From baseline to Week 12 and to Week 24 ]
    Percent change in fasting triglycerides (TG) from baseline to Week 12 and to Week 24
  • Percent change in Apo A-1 [ Time Frame: 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
  • Number of patients with adverse events [ Time Frame: Up to Week 104 ]
    Number of patients with adverse events
  • Cogstate battery test [ Time Frame: At Day 1, Weeks 24, 68, and 104 ]
    The Cogstate battery test will assess maturing cognition across a broad number of key developmental functions
  • Tanner stage [ Time Frame: At Weeks 24, 44, 68, and 104 ]
    The Tanner stages will be measured to assess stages of pubertal development -
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE An Efficacy and Safety Study of Alirocumab in Children and Adolescents With Heterozygous Familial Hypercholesterolemia
Official Title  ICMJE 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
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.
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Hypercholesterolaemia
Intervention  ICMJE
  • Drug: Alirocumab SAR236553 (REGN727)
    Pharmaceutical form:solution Route of administration: subcutaneous injection
    Other Name: 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
  • Drug: Placebo
    Pharmaceutical form:solution Route of administration: subcutaneous injection
Study Arms  ICMJE
  • 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.
    Interventions:
    • Drug: Alirocumab SAR236553 (REGN727)
    • Drug: Rosuvastatin
    • Drug: Atorvastatin
    • Drug: Simvastatin
    • Drug: Pravastatin
    • Drug: Lovastatin
    • Drug: Fluvastatin
    • Drug: Ezetimibe
    • Drug: Cholestyramine
    • Drug: Nicotinic acid
    • Drug: Fenofibrate
    • Drug: Omega-3 fatty acids
  • Placebo Comparator: Palcebo
    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
    Interventions:
    • Drug: Rosuvastatin
    • Drug: Atorvastatin
    • Drug: Simvastatin
    • Drug: Pravastatin
    • Drug: Lovastatin
    • Drug: Fluvastatin
    • Drug: Ezetimibe
    • Drug: Cholestyramine
    • Drug: Nicotinic acid
    • Drug: Fenofibrate
    • Drug: Omega-3 fatty acids
    • Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 18, 2018)
150
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE February 2022
Estimated Primary Completion Date February 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 kg.
  • 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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 8 Years to 17 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Trial Transparency email recommended (Toll free number for US & Canada) 800-633-1610 ext 1 then # Contact-Us@sanofi.com
Listed Location Countries  ICMJE Argentina,   Austria,   Brazil,   Bulgaria,   Canada,   Czechia,   Denmark,   Finland,   France,   Hungary,   Italy,   Lebanon,   Mexico,   Netherlands,   Norway,   Poland,   Russian Federation,   Slovenia,   South Africa,   Spain,   Sweden,   Taiwan,   Turkey,   United States
Removed Location Countries Germany
 
Administrative Information
NCT Number  ICMJE NCT03510884
Other Study ID Numbers  ICMJE EFC14643
2017-001903-60 ( EudraCT Number )
U1111-1193-0721 ( Other Identifier: UTN )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Sanofi
Study Sponsor  ICMJE Sanofi
Collaborators  ICMJE Regeneron Pharmaceuticals
Investigators  ICMJE
Study Director: Clinical Sciences & Operations Sanofi
PRS Account Sanofi
Verification Date November 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP