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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)

Primary Purpose

Hypercholesterolaemia

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

alirocumab SAR236553 (REGN727)

statins

ezetimibe

cholestyramine

fenofibrate

omega-3 fatty acids

nicotinic acid

About this trial

This is an interventional treatment trial for Hypercholesterolaemia

Eligibility Criteria

8 Years - 17 Years (Child)All SexesDoes not accept healthy volunteers

Inclusion criteria :

Children and adolescent male and female participants aged of 8 to 17 years at the time of signed informed consent. For Russia only: Male and female participants aged >=12 and <=17 years at the time of signed informed consent.
Participants with diagnosis of heterozygous familial hypercholesterolemia (heFH) through genotyping or clinical criteria.
Participants 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.
Participants with calculated LDL-C greater than or equal to 130 mg/dL (>=3.37 mmol/L) at the screening visit.
Participants with body weight greater than or equal to 25 kg.
Participants aged of 8 to 9 years to be at Tanner stage 1 and participants aged 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 participant assent.

Exclusion criteria:

Participant with secondary hyperlipidemia.
Diagnosis of homozygous familial hypercholesterolemia.
Participant who had 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 (i.e., 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 participant's potential participation in a clinical trial.

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm Type

Experimental

Arm Label

Cohort 1 - Alirocumab 30 mg Q2W: <50 kg

Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg

Cohort 2 - Alirocumab 40 mg Q2W: <50 kg

Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg

Cohort 3 - Alirocumab 75 mg Q4W: <50 kg

Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg

Cohort 4 - Alirocumab 150 mg Q4W: <50 kg

Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg

Arm Description

Period 1: Participants with body weight less than (<) 50 kilograms (kg) received subcutaneous (SC) injection of alirocumab 30 milligram(mg) administered every 2 weeks (Q2W) up to 8 weeks added to lipid modifying therapy (LMT). Period 2: Participants with body weight < 50 kg received SC injection of alirocumab 30 mg administered Q2W from Week 16 until they started receiving dose matching to Cohort 2 dosage including dose adjustment to body weight as required. Cohort 2 dosage was: if body weight was still < 50 kg, participants received SC injection of alirocumab 40 mg administered Q2W until Week 130; if body weight was > = 50 kg participants received SC injection of alirocumab 75 mg administered Q2W until Week 130.

Period 1: Participants with body weight greater than or equal to (>=) 50 kg received SC injection of alirocumab 50 mg administered Q2W up to 8 weeks added to LMT. Period 2: Participants with body weight >= 50 kg received SC injection of alirocumab 50 mg administered Q2W from Week 16 until switch to Cohort 2 dosage then SC injection of alirocumab 75 mg administered Q2W until Week 130.

Period 1: Participants with body weight < 50 kg received SC injection of alirocumab 40 mg administered Q2W up to 8 weeks added to LMT. Period 2: Participants with body weight < 50 kg received SC injection of alirocumab 40 mg administered Q2W from Week 16 until switch of dosage in Cohorts 1 and 3. If body weight was still < 50 kg, participants continued to receive SC injection of alirocumab 40 mg administered Q2W until Week 130; if body weight was > = 50 kg participants received SC injection of alirocumab 75 mg administered Q2W until Week 130.

Period 1: Participants with body weight >= 50 kg received SC injection of alirocumab 75 mg administered Q2W up to 8 weeks added to LMT. Period 2: Participants with body weight >= 50 kg received SC injection of alirocumab 75 mg administered Q2W from Week 16 until Week 130.

Period 1: Participants with body weight < 50 kg received SC injection of alirocumab 75 mg administered every 4 weeks (Q4W) up to 8 weeks added to LMT. Period 2: Participants with body weight < 50 kg received SC injection of alirocumab 75 mg administered Q4W from Week 14 until switch to Cohort 2 dosage including dose adjustment to body weight as required, then Cohort 2 dosage: if body weight was still < 50 kg, participants received SC injection of alirocumab 40 mg administered Q2W until Week 130; if body weight was > = 50 kg participants received SC injection of alirocumab 75 mg administered Q2W until Week 130.

Period 1: Participants with body weight >= 50 kg received SC injection of alirocumab 150 mg administered Q4W up to Week 8 added to LMT. Period 2: Participants with body weight >= 50 kg received SC injection of alirocumab 150 mg administered Q4W from Week 14 until switch to Cohort 2 dosage then SC injection of alirocumab 75 mg administered Q2W until Week 130.

Period 1: Participants with body weight < 50 kg received SC injection of alirocumab 150 mg administered Q4W up to 12 weeks added to LMT. Period 2: Participants with body weight < 50 kg received SC injection of Alirocumab 150 mg administered Q4W from Week 12 until Week 48.

Period 1: Participants with body weight >= 50 kg received SC injection of alirocumab 300 mg administered Q4W up to 12 weeks added to LMT. Period 2: Participants with body weight >= 50 kg received SC injection of alirocumab 300 mg administered Q4W from Week 12 until Week 48.

Outcomes

Primary Outcome Measures

Percent Change From Baseline in Calculated Low Density Lipoprotein Cholesterol (LDL-C) at Week 8

Percent change in calculated LDL-C was defined as 100*(calculated LDL-C value at Week 8 - calculated LDL-C value at baseline)/calculated LDL-C value at baseline. All available baseline and post-baseline calculated LDL-C value during the OLDFI efficacy treatment period & within one of the analysis windows up to Week 8 were used in the model. OLDFI efficacy treatment period was defined as the period from first investigational medicinal product (IMP) injection to last OLDFI IMP injection + 21 days(for Cohorts 1 & 2) or +35 days (for Cohorts 3 & 4). Adjusted Least-squares (LS) mean & standard error (SE) at Week 8 were obtained from mixed-effect model with repeated measures (MMRM) analysis, with fixed categorical effects of alirocumab dose/dose regimen (30 mg Q2W [<50 kg], 40 mg Q2W [<50 kg], 50 mg Q2W [>=50 kg], 75 mg Q2W [>=50 kg], 75 mg Q4W [<50 kg],150 mg Q4W [>=50 kg], 150 mg Q4W [<50 kg] and 300 mg Q4W ([>=50 kg] dose), time point & dose/dose regimen-by-time point interaction.

Secondary Outcome Measures

Absolute Change From Baseline in Calculated Low Density Lipoprotein Cholesterol (LDL-C) at Week 8

Absolute change in LDL-C was calculated by subtracting baseline value from Week 8 value. Adjusted LS means and SE were obtained using MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction.

Percentage of Participants Achieving Calculated Low Density Lipoprotein Cholesterol (LDL-C) <130 mg/dL (3.37 mmol/L) at Week 8

Combined estimate for percentage of participants was obtained by averaging out all the imputed percentage of participants reaching the level of interest. A two-step multiple imputation procedure was used to address missing values in the mITT population in the two steps respectively; with number of imputations = 1000. In the first step, the monotone missing pattern was induced in the multiply-imputed data. In the second step, the missing data at subsequent visits were imputed using the regression method for continuous variables.

Percentage of Participants Achieving Calculated LDL-C <110 mg/dL (2.84 mmol/L) at Week 8

Percent Change From Baseline in Calculated LDL-C at Week 12: Cohort 4

Adjusted LS means and standard error at Week 12 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction.

Percent Change From Baseline in Apolipoprotein (Apo) B at Week 8

Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. All available baseline value and post-baseline values in at least one of the analysis windows used in the model.

Percent Change From Baseline in Non-High Density Lipoprotein (HDL-C) at Week 8

Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. All available baselines value and post-baseline values in at least one of the analysis windows up to Week 8 were used in the model.

Percent Change From Baseline in Total Cholesterol (Total-C) at Week 8

Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. All available baseline values and post-baseline values in at least one of the analysis windows up to Week 8 were used in the model.

Percent Change From Baseline in Lipoprotein(a) at Week 8

Combined estimates and SE were obtained by combining adjusted means and SE from robust regression model analyses of the different imputed data sets. The robust regression models included the fixed categorical effect of alirocumab dose/dose regimen. A two-step multiple imputation procedure was used to address missing values in the mITT population in the two steps respectively (with number of imputations = 1000). In the first step, the monotone missing pattern was induced in the multiply-imputed data. In the second step, the missing data at subsequent visits were imputed using the regression method for continuous variables.

Percent Change From Baseline in Fasting Triglyceride at Week 8

Combined estimates and SE were obtained by combining adjusted means and SE from robust regression model analyses of the different imputed data sets. The robust regression models included the fixed categorical effect of alirocumab dose/dose regimen. A two-step multiple imputation procedure was used to address missing values in the mITT population (in the two steps respectively; with number of imputations = 1000). In the first step, the monotone missing pattern was induced in the multiply-imputed data. In the second step, the missing data at subsequent visits were imputed using the regression method for continuous variables.

Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at Week 8

Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. All available baseline values and post-baseline values in at least one of the analysis windows up to Week 8 were used in the model.

Percent Change From Baseline in Apolipoprotein A-1 at Week 8

Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. All available baseline values and post-baseline values in at least one of the analysis windows up to Week 8 were used in the model.

Absolute Change From Baseline in Apolipoprotein B at Week 8

Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. All available baseline values and post-baseline values in at least one of the analysis windows up to Week 8 were used in the model.

Absolute Change From Baseline in Non-High-Density Lipoprotein (Non-HDL-C) at Week 8

Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. All available baseline values and post-baseline values in at least one of the analysis windows up to Week 8 were used in the model.

Absolute Change From Baseline in Total Cholesterol (Total-C) at Week 8

Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. All available baseline values and post-baseline values in at least one of the analysis windows up to Week 8 were used in the model.

Absolute Change From Baseline in Lipoprotein(a) at Week 8

Combined estimates and SE were obtained by combining adjusted means and SE from robust regression model analyses of the different imputed data sets. The robust regression models included the fixed categorical effect of alirocumab dose/dose regimen. A two-step multiple imputation procedure was used to address missing values in the mITT population (in the two steps respectively; with number of imputations = 1000). In the first step, the monotone missing pattern was induced in the multiply-imputed data. In the second step, the missing data at subsequent visits were imputed using the regression method for continuous variables.

Absolute Change From Baseline in HDL-C at Week 8

Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. All available baseline values and post-baseline values in at least one of the analysis windows up to Week 8 were used in the model.

Absolute Change From Baseline in Fasting Triglyceride at Week 8

Combined estimates and SE were obtained by combining adjusted means and SE from robust regression model analyses of the different imputed data sets. The robust regression models included the fixed categorical effect of alirocumab dose/dose regimen. A two-step multiple imputation procedure was used to address missing values in the mITT population (in the two steps respectively; with number of imputations = 1000). In the first step, the monotone missing pattern was induced in the multiply-imputed data. In the second step, the missing data at subsequent visits were imputed using the regression method for continuous variables.

Absolute Change From Baseline in Apolipoprotein A-1 at Week 8

Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. All available baseline values and post-baseline values in at least one of the analysis windows up to Week 8 were used in the model.

Absolute Change From Baseline in Ratio Apolipoprotein B/Apolipoprotein A-1 at Week 8

Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. All available baseline values and post-baseline values in at least one of the analysis windows up to Week 8 were used in the model.

Full Information

NCT ID

NCT02890992

First Posted

August 31, 2016

Last Updated

August 15, 2019

Sponsor

Sanofi

Collaborators

Regeneron Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT02890992

Brief Title

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

Acronym

ODYSSEY KIDS

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 Type

Interventional

2. Study Status

Record Verification Date

August 2019

Overall Recruitment Status

Completed

Study Start Date

September 15, 2016 (Actual)

Primary Completion Date

September 13, 2018 (Actual)

Study Completion Date

February 22, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Sanofi

Collaborators

Regeneron Pharmaceuticals

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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) participants aged of 8 to 17 years, with LDL-C >=130 milligrams per deciliter (mg/dL) (3.37 millimoles per litre [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.

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 participants enrolled in Cohorts 1 to 3, but a maximum of approximately 5 months for the first participants enrolled in Cohort 4. For all participants who declined participation in the phase 3 study, their last alirocumab injection was on December 2018.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hypercholesterolaemia

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Sequential Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

42 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Cohort 1 - Alirocumab 30 mg Q2W: <50 kg

Arm Type

Experimental

Arm Description

Arm Title

Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg

Arm Type

Experimental

Arm Description

Arm Title

Cohort 2 - Alirocumab 40 mg Q2W: <50 kg

Arm Type

Experimental

Arm Description

Arm Title

Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg

Arm Type

Experimental

Arm Description

Arm Title

Cohort 3 - Alirocumab 75 mg Q4W: <50 kg

Arm Type

Experimental

Arm Description

Arm Title

Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg

Arm Type

Experimental

Arm Description

Arm Title

Cohort 4 - Alirocumab 150 mg Q4W: <50 kg

Arm Type

Experimental

Arm Description

Arm Title

Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

alirocumab SAR236553 (REGN727)

Other Intervention Name(s)

Praluent

Intervention Description

Pharmaceutical form: solution Route of administration: subcutaneous injection

Intervention Type

Drug

Intervention Name(s)

statins

Intervention Description

Pharmaceutical form: tablet Route of administration: oral

Intervention Type

Drug

Intervention Name(s)

ezetimibe

Intervention Description

Pharmaceutical form:tablet Route of administration: oral

Intervention Type

Drug

Intervention Name(s)

cholestyramine

Intervention Description

Pharmaceutical form:tablet Route of administration: oral

Intervention Type

Drug

Intervention Name(s)

fenofibrate

Intervention Description

Pharmaceutical form: tablet Route of administration: oral

Intervention Type

Drug

Intervention Name(s)

omega-3 fatty acids

Intervention Description

Pharmaceutical form: tablet Route of administration: oral

Intervention Type

Drug

Intervention Name(s)

nicotinic acid

Intervention Description

Pharmaceutical form: tablet Route of administration: oral

Primary Outcome Measure Information:

Title

Percent Change From Baseline in Calculated Low Density Lipoprotein Cholesterol (LDL-C) at Week 8

Description

Time Frame

Baseline, Week 8

Secondary Outcome Measure Information:

Title

Absolute Change From Baseline in Calculated Low Density Lipoprotein Cholesterol (LDL-C) at Week 8

Description

Time Frame

Baseline, Week 8

Title

Percentage of Participants Achieving Calculated Low Density Lipoprotein Cholesterol (LDL-C) <130 mg/dL (3.37 mmol/L) at Week 8

Description

Time Frame

At Week 8

Title

Percentage of Participants Achieving Calculated LDL-C <110 mg/dL (2.84 mmol/L) at Week 8

Description

Time Frame

At Week 8

Title

Percent Change From Baseline in Calculated LDL-C at Week 12: Cohort 4

Description

Time Frame

Baseline, Week 12

Title

Percent Change From Baseline in Apolipoprotein (Apo) B at Week 8

Description

Time Frame

Baseline, Week 8

Title

Percent Change From Baseline in Non-High Density Lipoprotein (HDL-C) at Week 8

Description

Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. All available baselines value and post-baseline values in at least one of the analysis windows up to Week 8 were used in the model.

Time Frame

Baseline, Week 8

Title

Percent Change From Baseline in Total Cholesterol (Total-C) at Week 8

Description

Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. All available baseline values and post-baseline values in at least one of the analysis windows up to Week 8 were used in the model.

Time Frame

Baseline, Week 8

Title

Percent Change From Baseline in Lipoprotein(a) at Week 8

Description

Time Frame

Baseline, Week 8

Title

Percent Change From Baseline in Fasting Triglyceride at Week 8

Description

Combined estimates and SE were obtained by combining adjusted means and SE from robust regression model analyses of the different imputed data sets. The robust regression models included the fixed categorical effect of alirocumab dose/dose regimen. A two-step multiple imputation procedure was used to address missing values in the mITT population (in the two steps respectively; with number of imputations = 1000). In the first step, the monotone missing pattern was induced in the multiply-imputed data. In the second step, the missing data at subsequent visits were imputed using the regression method for continuous variables.

Time Frame

Baseline, Week 8

Title

Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at Week 8

Description

Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. All available baseline values and post-baseline values in at least one of the analysis windows up to Week 8 were used in the model.

Time Frame

Baseline, Week 8

Title

Percent Change From Baseline in Apolipoprotein A-1 at Week 8

Description

Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. All available baseline values and post-baseline values in at least one of the analysis windows up to Week 8 were used in the model.

Time Frame

Baseline, Week 8

Title

Absolute Change From Baseline in Apolipoprotein B at Week 8

Description

Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. All available baseline values and post-baseline values in at least one of the analysis windows up to Week 8 were used in the model.

Time Frame

Baseline, Week 8

Title

Absolute Change From Baseline in Non-High-Density Lipoprotein (Non-HDL-C) at Week 8

Description

Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. All available baseline values and post-baseline values in at least one of the analysis windows up to Week 8 were used in the model.

Time Frame

Baseline, Week 8

Title

Absolute Change From Baseline in Total Cholesterol (Total-C) at Week 8

Description

Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. All available baseline values and post-baseline values in at least one of the analysis windows up to Week 8 were used in the model.

Time Frame

Baseline, Week 8

Title

Absolute Change From Baseline in Lipoprotein(a) at Week 8

Description

Combined estimates and SE were obtained by combining adjusted means and SE from robust regression model analyses of the different imputed data sets. The robust regression models included the fixed categorical effect of alirocumab dose/dose regimen. A two-step multiple imputation procedure was used to address missing values in the mITT population (in the two steps respectively; with number of imputations = 1000). In the first step, the monotone missing pattern was induced in the multiply-imputed data. In the second step, the missing data at subsequent visits were imputed using the regression method for continuous variables.

Time Frame

Baseline, Week 8

Title

Absolute Change From Baseline in HDL-C at Week 8

Description

Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. All available baseline values and post-baseline values in at least one of the analysis windows up to Week 8 were used in the model.

Time Frame

Baseline, Week 8

Title

Absolute Change From Baseline in Fasting Triglyceride at Week 8

Description

Combined estimates and SE were obtained by combining adjusted means and SE from robust regression model analyses of the different imputed data sets. The robust regression models included the fixed categorical effect of alirocumab dose/dose regimen. A two-step multiple imputation procedure was used to address missing values in the mITT population (in the two steps respectively; with number of imputations = 1000). In the first step, the monotone missing pattern was induced in the multiply-imputed data. In the second step, the missing data at subsequent visits were imputed using the regression method for continuous variables.

Time Frame

Baseline, Week 8

Title

Absolute Change From Baseline in Apolipoprotein A-1 at Week 8

Description

Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. All available baseline values and post-baseline values in at least one of the analysis windows up to Week 8 were used in the model.

Time Frame

Baseline, Week 8

Title

Absolute Change From Baseline in Ratio Apolipoprotein B/Apolipoprotein A-1 at Week 8

Description

Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. All available baseline values and post-baseline values in at least one of the analysis windows up to Week 8 were used in the model.

Time Frame

Baseline, Week 8

10. Eligibility

Sex

All

Minimum Age & Unit of Time

8 Years

Maximum Age & Unit of Time

17 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion criteria : Children and adolescent male and female participants aged of 8 to 17 years at the time of signed informed consent. For Russia only: Male and female participants aged >=12 and <=17 years at the time of signed informed consent. Participants with diagnosis of heterozygous familial hypercholesterolemia (heFH) through genotyping or clinical criteria. Participants 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. Participants with calculated LDL-C greater than or equal to 130 mg/dL (>=3.37 mmol/L) at the screening visit. Participants with body weight greater than or equal to 25 kg. Participants aged of 8 to 9 years to be at Tanner stage 1 and participants aged 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 participant assent. Exclusion criteria: Participant with secondary hyperlipidemia. Diagnosis of homozygous familial hypercholesterolemia. Participant who had 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 (i.e., 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 participant's potential participation in a clinical trial.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Clinical Sciences & Operations

Organizational Affiliation

Sanofi

Official's Role

Study Director

Facility Information:

Facility Name

Investigational Site Number 8400002

City

Saint Louis

State/Province

Missouri

ZIP/Postal Code

63110

Country

United States

Facility Name

Investigational Site Number 8400005

City

Charlotte

State/Province

North Carolina

ZIP/Postal Code

28204

Country

United States

Facility Name

Investigational Site Number 8400001

City

Cincinnati

State/Province

Ohio

ZIP/Postal Code

45229

Country

United States

Facility Name

Investigational Site Number 1240001

City

Quebec

ZIP/Postal Code

G1V 4W2

Country

Canada

Facility Name

Investigational Site Number 2030001

City

Brno

ZIP/Postal Code

62500

Country

Czechia

Facility Name

Investigational Site Number 2030003

City

Praha 5 - Motol

ZIP/Postal Code

15006

Country

Czechia

Facility Name

Investigational Site Number 2030002

City

Zlin

ZIP/Postal Code

76275

Country

Czechia

Facility Name

Investigational Site Number 2500001

City

Bron Cedex

ZIP/Postal Code

69677

Country

France

Facility Name

Investigational Site Number 5280001

City

Amsterdam

ZIP/Postal Code

1105AZ

Country

Netherlands

Facility Name

Investigational Site Number 5780001

City

Oslo

Country

Norway

Facility Name

Investigational Site Number 6430001

City

Kemerovo

ZIP/Postal Code

650002

Country

Russian Federation

Facility Name

Investigational Site Number 6430004

City

Saint-Petersburg

ZIP/Postal Code

194100

Country

Russian Federation

Facility Name

Investigational Site Number 7100001

City

Parow

ZIP/Postal Code

7500

Country

South Africa

Facility Name

Investigational Site Number 7240004

City

A Coruna

ZIP/Postal Code

15001

Country

Spain

Facility Name

Investigational Site Number 7240001

City

Madrid

ZIP/Postal Code

28009

Country

Spain

Facility Name

Investigational Site Number 7520001

City

Stockholm

ZIP/Postal Code

171 76

Country

Sweden

12. IPD Sharing Statement

Citations:

PubMed Identifier

32331936

Citation

Daniels S, Caprio S, Chaudhari U, Manvelian G, Baccara-Dinet MT, Brunet A, Scemama M, Loizeau V, Bruckert E. PCSK9 inhibition with alirocumab in pediatric patients with heterozygous familial hypercholesterolemia: The ODYSSEY KIDS study. J Clin Lipidol. 2020 May-Jun;14(3):322-330.e5. doi: 10.1016/j.jacl.2020.03.001. Epub 2020 Mar 28. Erratum In: J Clin Lipidol. 2020 Sep - Oct;14(5):741.

Results Reference

derived

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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

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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)

Hypercholesterolaemia

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial