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An 8-Week Dose-Finding Study to Evaluate the Efficacy and Safety of Alirocumab in Children and Adolescents With Heterozygous Familial Hypercholesterolemia (ODYSSEY KIDS)

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ClinicalTrials.gov Identifier: NCT02890992
Recruitment Status : Recruiting
First Posted : September 7, 2016
Last Update Posted : January 19, 2018
Sponsor:
Collaborator:
Regeneron Pharmaceuticals
Information provided by (Responsible Party):
Sanofi

Brief Summary:

Primary Objective:

To evaluate the effect of alirocumab on low-density lipoprotein cholesterol (LDL-C) levels after 8 weeks of treatment in heterozygous familial hypercholesterolemia (heFH) patients age of 8 to 17 years, with LDL-C ≥130 mg/dL (3.37 mmol/L) 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 for at least 4 weeks prior to the screening period.

Secondary Objective:

  • To evaluate the safety and tolerability of alirocumab.
  • To evaluate the pharmacokinetics profile of alirocumab.
  • To evaluate the effects of alirocumab on other lipid parameters.

Condition or disease Intervention/treatment Phase
Hypercholesterolaemia Drug: alirocumab SAR236553 (REGN727) Drug: statins Drug: ezetimibe Drug: cholestyramine Drug: fenofibrate Drug: omega-3 fatty acids Drug: nicotinic acid Phase 2

Detailed Description:

For Cohorts 1 to 3, a study duration of approximately 16-23 weeks (screening period: up to 6 (+1) weeks, open-label dose finding treatment period: 8 weeks, follow up period: 6-8 weeks).

For Cohort 4, a study duration of approximately 14-19 weeks (screening period up to 6 [+1] weeks, open-label dose finding treatment period: 12 weeks).

Optional extension period: up to a maximum of 2 years for the first patients enrolled in Cohorts 1 to 3, but a maximum of approximately 5 months for the first patients enrolled in Cohort 4.

For all patients who decline participation in the phase 3 study, their last alirocumab injection will be on December 2018.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An 8-Week Open-Label, Sequential, Repeated Dose-Finding Study to Evaluate the Efficacy and Safety of Alirocumab in Children and Adolescents With Heterozygous Familial Hypercholesterolemia Followed by an Extension Phase
Study Start Date : September 15, 2016
Estimated Primary Completion Date : October 2018
Estimated Study Completion Date : February 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Alirocumab
U.S. FDA Resources

Arm Intervention/treatment
Experimental: Cohort 1 - Dose 1
Alirocumab Dose 1 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: statins
Pharmaceutical form: tablet Route of administration: oral
Drug: ezetimibe
Pharmaceutical form:tablet Route of administration: oral
Drug: cholestyramine
Pharmaceutical form:tablet Route of administration: oral
Drug: fenofibrate
Pharmaceutical form: tablet Route of administration: oral
Drug: omega-3 fatty acids
Pharmaceutical form: tablet Route of administration: oral
Drug: nicotinic acid
Pharmaceutical form: tablet Route of administration: oral
Experimental: Cohort 1 - Dose 2
Alirocumab Dose 2 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: alirocumab SAR236553 (REGN727)
Pharmaceutical form: solution Route of administration: subcutaneous injection
Other Name: Praluent
Drug: statins
Pharmaceutical form: tablet Route of administration: oral
Drug: ezetimibe
Pharmaceutical form:tablet Route of administration: oral
Drug: cholestyramine
Pharmaceutical form:tablet Route of administration: oral
Drug: fenofibrate
Pharmaceutical form: tablet Route of administration: oral
Drug: omega-3 fatty acids
Pharmaceutical form: tablet Route of administration: oral
Drug: nicotinic acid
Pharmaceutical form: tablet Route of administration: oral
Experimental: Cohort 2 - Dose 3
Alirocumab Dose 3 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: alirocumab SAR236553 (REGN727)
Pharmaceutical form: solution Route of administration: subcutaneous injection
Other Name: Praluent
Drug: statins
Pharmaceutical form: tablet Route of administration: oral
Drug: ezetimibe
Pharmaceutical form:tablet Route of administration: oral
Drug: cholestyramine
Pharmaceutical form:tablet Route of administration: oral
Drug: fenofibrate
Pharmaceutical form: tablet Route of administration: oral
Drug: omega-3 fatty acids
Pharmaceutical form: tablet Route of administration: oral
Drug: nicotinic acid
Pharmaceutical form: tablet Route of administration: oral
Experimental: Cohort 2 - Dose 4
Experimental - Alirocumab Dose 4 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: alirocumab SAR236553 (REGN727)
Pharmaceutical form: solution Route of administration: subcutaneous injection
Other Name: Praluent
Drug: statins
Pharmaceutical form: tablet Route of administration: oral
Drug: ezetimibe
Pharmaceutical form:tablet Route of administration: oral
Drug: cholestyramine
Pharmaceutical form:tablet Route of administration: oral
Drug: fenofibrate
Pharmaceutical form: tablet Route of administration: oral
Drug: omega-3 fatty acids
Pharmaceutical form: tablet Route of administration: oral
Drug: nicotinic acid
Pharmaceutical form: tablet Route of administration: oral
Experimental: Cohort 3 - Dose 5
Experimental - Alirocumab Dose 5 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: alirocumab SAR236553 (REGN727)
Pharmaceutical form: solution Route of administration: subcutaneous injection
Other Name: Praluent
Drug: statins
Pharmaceutical form: tablet Route of administration: oral
Drug: ezetimibe
Pharmaceutical form:tablet Route of administration: oral
Drug: cholestyramine
Pharmaceutical form:tablet Route of administration: oral
Drug: fenofibrate
Pharmaceutical form: tablet Route of administration: oral
Drug: omega-3 fatty acids
Pharmaceutical form: tablet Route of administration: oral
Drug: nicotinic acid
Pharmaceutical form: tablet Route of administration: oral
Experimental: Cohort 3 - Dose 6
Experimental - Alirocumab Dose 6 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: alirocumab SAR236553 (REGN727)
Pharmaceutical form: solution Route of administration: subcutaneous injection
Other Name: Praluent
Drug: statins
Pharmaceutical form: tablet Route of administration: oral
Drug: ezetimibe
Pharmaceutical form:tablet Route of administration: oral
Drug: cholestyramine
Pharmaceutical form:tablet Route of administration: oral
Drug: fenofibrate
Pharmaceutical form: tablet Route of administration: oral
Drug: omega-3 fatty acids
Pharmaceutical form: tablet Route of administration: oral
Drug: nicotinic acid
Pharmaceutical form: tablet Route of administration: oral
Experimental: Cohort 4 - Dose 7
Alirocumab Dose 7 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: alirocumab SAR236553 (REGN727)
Pharmaceutical form: solution Route of administration: subcutaneous injection
Other Name: Praluent
Drug: statins
Pharmaceutical form: tablet Route of administration: oral
Drug: ezetimibe
Pharmaceutical form:tablet Route of administration: oral
Drug: cholestyramine
Pharmaceutical form:tablet Route of administration: oral
Drug: fenofibrate
Pharmaceutical form: tablet Route of administration: oral
Drug: omega-3 fatty acids
Pharmaceutical form: tablet Route of administration: oral
Drug: nicotinic acid
Pharmaceutical form: tablet Route of administration: oral
Experimental: Cohort 4 - Dose 8
Alirocumab Dose 8 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: alirocumab SAR236553 (REGN727)
Pharmaceutical form: solution Route of administration: subcutaneous injection
Other Name: Praluent
Drug: statins
Pharmaceutical form: tablet Route of administration: oral
Drug: ezetimibe
Pharmaceutical form:tablet Route of administration: oral
Drug: cholestyramine
Pharmaceutical form:tablet Route of administration: oral
Drug: fenofibrate
Pharmaceutical form: tablet Route of administration: oral
Drug: omega-3 fatty acids
Pharmaceutical form: tablet Route of administration: oral
Drug: nicotinic acid
Pharmaceutical form: tablet Route of administration: oral



Primary Outcome Measures :
  1. Percent change in calculated low-density lipoprotein cholesterol (LDL-C) [ Time Frame: From baseline to Week 8 ]

Secondary Outcome Measures :
  1. Absolute change in calculated LDL-C [ Time Frame: From baseline to Week 8 ]
  2. Proportion of patients achieving a calculated LDL-C <130 mg/dL (3.37 mmol/L) [ Time Frame: At Week 8 ]
  3. Proportion of patients achieving a calculated LDL-C level <110 mg/dL (2.84 mmol/L) [ Time Frame: At Week 8 ]
  4. Percent change in calculated LDL-C (for Cohort 4) [ Time Frame: From baseline to Week 8 ]
  5. Percent change in Apolipoprotein B (Apo B) [ Time Frame: From baseline to Week 8 ]
  6. Percent change in non-high density lipoprotein cholesterol (non HDL-C) [ Time Frame: From baseline to Week 8 ]
  7. Percent change in Total-C [ Time Frame: From baseline to Week 8 ]
  8. Percent change in Lipoprotein (a) (Lp[a]) [ Time Frame: From baseline to Week 8 ]
  9. Percent change in triglycerides (TG) [ Time Frame: From baseline to Week 8 ]
  10. Percent change in HDL-C [ Time Frame: From baseline to Week 8 ]
  11. Percent change in Apo A-1 [ Time Frame: From baseline to Week 8 ]
  12. Absolute change in Apo B [ Time Frame: From baseline to Week 8 ]
  13. Absolute change in non-HDL-C [ Time Frame: From baseline to Week 8 ]
  14. Absolute change in Total-C [ Time Frame: From baseline to Week 8 ]
  15. Absolute change in Lp(a) [ Time Frame: From baseline to Week 8 ]
  16. Absolute change in HDL-C [ Time Frame: From baseline to Week 8 ]
  17. Absolute change in TG [ Time Frame: From baseline to Week 8 ]
  18. Absolute change in Apo A-1 [ Time Frame: From baseline to Week 8 ]
  19. Absolute change in ratio Apo B/Apo A-1 [ Time Frame: From baseline to Week 8 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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 age of 8 to 17 years at the time of signed informed consent. For Russia only: Male and female patients aged ≥12 and ≤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.
  • Patients with body weight greater than or equal to 25kg.
  • Patients age of 8 to 9 years to be at Tanner stage 1 and patients age of 10 to 17 years to be at least at Tanner stage 2 in their development.
  • A signed informed consent indicating parental permission with or without patient assent.

Exclusion criteria:

  • Patient 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.
  • Known history of type 1 or type 2 diabetes mellitus.
  • Known history of thyroid disease.
  • Known history of hypertension.
  • Fasting triglycerides >350 mg/dL (3.95 mmol/L).
  • Severe renal impairment (ie, estimated glomerular filtration rate [eGFR] <30 mL/min/1.73 m².
  • 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): NCT02890992


Contacts
Contact: For site information, send an email with site number to Contact-Us@sanofi.com

Locations
United States, Missouri
Investigational Site Number 8400002 Active, not recruiting
Saint Louis, Missouri, United States, 63110
United States, North Carolina
Investigational Site Number 8400005 Recruiting
Charlotte, North Carolina, United States, 28204
United States, Ohio
Investigational Site Number 8400001 Active, not recruiting
Cincinnati, Ohio, United States, 45229
Canada
Investigational Site Number 1240001 Active, not recruiting
Quebec, Canada, G1V 4W2
Czechia
Investigational Site Number 2030001 Active, not recruiting
Brno, Czechia, 62500
Investigational Site Number 2030003 Active, not recruiting
Praha 5 - Motol, Czechia, 15006
Investigational Site Number 2030002 Completed
Zlin, Czechia, 76275
France
Investigational Site Number 2500001 Active, not recruiting
Bron Cedex, France, 69677
Netherlands
Investigational Site Number 5280001 Active, not recruiting
Amsterdam, Netherlands, 1105 AZ
Norway
Investigational Site Number 5780001 Active, not recruiting
Oslo, Norway
Russian Federation
Investigational Site Number 6430001 Active, not recruiting
Kemerovo, Russian Federation, 650002
Investigational Site Number 6430004 Completed
Saint-Petersburg, Russian Federation, 194100
South Africa
Investigational Site Number 7100001 Active, not recruiting
Parow, South Africa, 7500
Spain
Investigational Site Number 7240004 Active, not recruiting
A Coruna, Spain, 15001
Investigational Site Number 7240001 Completed
Madrid, Spain, 28009
Sweden
Investigational Site Number 7520001 Active, not recruiting
Stockholm, Sweden, 171 76
Sponsors and Collaborators
Sanofi
Regeneron Pharmaceuticals
Investigators
Study Director: Clinical Sciences & Operations Sanofi

Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT02890992     History of Changes
Other Study ID Numbers: DFI14223
2015-003766-85 ( EudraCT Number )
U1111-1178-4764 ( Other Identifier: UTN )
First Posted: September 7, 2016    Key Record Dates
Last Update Posted: January 19, 2018
Last Verified: January 2018

Additional relevant MeSH terms:
Hypercholesterolemia
Hyperlipoproteinemia Type II
Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Lipid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Hyperlipoproteinemias
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Ezetimibe
Cholestyramine Resin
Fenofibrate
Niacin
Antibodies, Monoclonal
Nicotinic Acids
Niacinamide
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors
Lipid Regulating Agents
Immunologic Factors
Physiological Effects of Drugs
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances