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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 : June 21, 2019
Sponsor:
Collaborator:
Regeneron Pharmaceuticals
Information provided by (Responsible Party):
Sanofi

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
Hypercholesterolaemia 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 Drug: Placebo 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).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 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
Estimated Primary Completion Date : February 2022
Estimated Study Completion Date : February 2022

Resource links provided by the National Library of Medicine

Drug Information available for: Alirocumab

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 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

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
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




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. Percent change in LDL-C [ Time Frame: From baseline to Week 12 ]
    Percent change in LDL-C from baseline to Week 12

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

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

  12. 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

  13. Tanner stage [ Time Frame: At Weeks 24, 44, 68, and 104 ]
    The Tanner stages will be measured to assess stages of pubertal development -



Information from the National Library of Medicine

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Ages Eligible for Study:   8 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03510884


Contacts
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Contact: Trial Transparency email recommended (Toll free number for US & Canada) 800-633-1610 ext 1 then # Contact-Us@sanofi.com

  Show 48 Study Locations
Sponsors and Collaborators
Sanofi
Regeneron Pharmaceuticals
Investigators
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Study Director: Clinical Sciences & Operations Sanofi

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Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT03510884     History of Changes
Other Study ID Numbers: EFC14643
2017-001903-60 ( EudraCT Number )
U1111-1193-0721 ( Other Identifier: UTN )
First Posted: April 27, 2018    Key Record Dates
Last Update Posted: June 21, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Cholestyramine Resin
Hypercholesterolemia
Hyperlipoproteinemia Type II
Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Lipid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Hyperlipoproteinemias
Atorvastatin
Rosuvastatin Calcium
Simvastatin
Ezetimibe
Pravastatin
Lovastatin
Fenofibrate
Niacin
Antibodies, Monoclonal
Nicotinic Acids
Niacinamide
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors
Immunologic Factors