HypercholesterolaemiaPhase 2ODYSSEY KIDSNCT02890992
An 8-Week Dose-Finding Study to Evaluate the Efficacy and Safety of Alirocumab in Children and Adolescents With Heterozygous Familial Hypercholesterolemia
A Phase 2 study testing alirocumab SAR236553 (REGN727), statins and ezetimibe in people with Hypercholesterolaemia, run by Sanofi at 16 sites in 10 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 8 to 17 years
- Conditions the study is for
- Hypercholesterolaemia
- What is being tested?
- alirocumab SAR236553 (REGN727), statins and ezetimibe
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 42 participants
- Where
- 16 sitesin 10 countries
- Study dates
- 15 Sep 2016to 22 Feb 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 8 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
16 sites in 10 countries.
16 sites in 10 countries
United States3 sites
Investigational Site Number 8400005
Charlotte, North Carolina, 28204
Investigational Site Number 8400001
Cincinnati, Ohio, 45229
Investigational Site Number 8400002
St Louis, Missouri, 63110
Czechia3 sites
Investigational Site Number 2030001
Brno, 62500
Investigational Site Number 2030003
Praha 5 - Motol, 15006
Investigational Site Number 2030002
Zlín, 76275
Russia2 sites
Investigational Site Number 6430001
Kemerovo, 650002
Investigational Site Number 6430004
Saint Petersburg, 194100
Spain2 sites
Investigational Site Number 7240004
A Coruña, 15001
Investigational Site Number 7240001
Madrid, 28009
About this study
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
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.
Read more
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.
Read the 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.
- Conditions
- Hypercholesterolaemia
- Being tested
- alirocumab SAR236553 (REGN727), statins, ezetimibe, cholestyramine, fenofibrate
- Medical subject headings
- Hypercholesterolemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
alirocumab SAR236553 (REGN727)Drug
Also called Praluent
Pharmaceutical form: solution Route of administration: subcutaneous injection
statinsDrug
Pharmaceutical form: tablet Route of administration: oral
ezetimibeDrug
Pharmaceutical form:tablet Route of administration: oral
cholestyramineDrug
Pharmaceutical form:tablet Route of administration: oral
fenofibrateDrug
Pharmaceutical form: tablet Route of administration: oral
omega-3 fatty acidsDrug
Pharmaceutical form: tablet Route of administration: oral
nicotinic acidDrug
Pharmaceutical form: tablet Route of administration: oral
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 - Alirocumab 30 mg Q2W: <50 kg | Experimental | 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. Receives: Drug: alirocumab SAR236553 (REGN727); Drug: statins; Drug: ezetimibe; Drug: cholestyramine; Drug: fenofibrate; Drug: omega-3 fatty acids; Drug: nicotinic acid |
| Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg | Experimental | 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. Receives: Drug: alirocumab SAR236553 (REGN727); Drug: statins; Drug: ezetimibe; Drug: cholestyramine; Drug: fenofibrate; Drug: omega-3 fatty acids; Drug: nicotinic acid |
| Cohort 2 - Alirocumab 40 mg Q2W: <50 kg | Experimental | 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. Receives: Drug: alirocumab SAR236553 (REGN727); Drug: statins; Drug: ezetimibe; Drug: cholestyramine; Drug: fenofibrate; Drug: omega-3 fatty acids; Drug: nicotinic acid |
| Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg | Experimental | 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. Receives: Drug: alirocumab SAR236553 (REGN727); Drug: statins; Drug: ezetimibe; Drug: cholestyramine; Drug: fenofibrate; Drug: omega-3 fatty acids; Drug: nicotinic acid |
| Cohort 3 - Alirocumab 75 mg Q4W: <50 kg | Experimental | 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. Receives: Drug: alirocumab SAR236553 (REGN727); Drug: statins; Drug: ezetimibe; Drug: cholestyramine; Drug: fenofibrate; Drug: omega-3 fatty acids; Drug: nicotinic acid |
| Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg | Experimental | 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. Receives: Drug: alirocumab SAR236553 (REGN727); Drug: statins; Drug: ezetimibe; Drug: cholestyramine; Drug: fenofibrate; Drug: omega-3 fatty acids; Drug: nicotinic acid |
| Cohort 4 - Alirocumab 150 mg Q4W: <50 kg | Experimental | 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. Receives: Drug: alirocumab SAR236553 (REGN727); Drug: statins; Drug: ezetimibe; Drug: cholestyramine; Drug: fenofibrate; Drug: omega-3 fatty acids; Drug: nicotinic acid |
| Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg | Experimental | 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. Receives: Drug: alirocumab SAR236553 (REGN727); Drug: statins; Drug: ezetimibe; Drug: cholestyramine; Drug: fenofibrate; Drug: omega-3 fatty acids; Drug: nicotinic acid |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline, Week 8
Secondary outcomes (19)
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.
Measured: Baseline, Week 8
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.
Measured: At Week 8
Percentage of Participants Achieving Calculated LDL-C <110 mg/dL (2.84 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.
Measured: 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.
Measured: Baseline, Week 12
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.
Measured: Baseline, Week 8
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.
Measured: Baseline, Week 8
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.
Measured: Baseline, Week 8
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.
Measured: Baseline, Week 8
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.
Measured: Baseline, Week 8
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.
Measured: Baseline, Week 8
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.
Measured: Baseline, Week 8
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.
Measured: Baseline, Week 8
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.
Measured: Baseline, Week 8
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.
Measured: Baseline, Week 8
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.
Measured: Baseline, Week 8
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.
Measured: Baseline, Week 8
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.
Measured: Baseline, Week 8
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.
Measured: Baseline, Week 8
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.
Measured: Baseline, Week 8
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Sep 2016 (estimated)
- Study start15 Sep 2016
- Primary completion13 Sep 2018
- Study completion22 Feb 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HypercholesterolaemiaStudies of the same condition, open and under way.
- More trials run by SanofiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 42 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sanofi
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Regeneron Pharmaceuticals
- Responsible party
- Sponsor
- Investigators
- Clinical Sciences & Operations, Study director, Sanofi
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02890992
- Sponsor's protocol ID
- DFI14223
- Other IDs
- 2015-003766-85, U1111-1178-4764, 2015
- Acronym
- ODYSSEY KIDS
- Status last verified
- Aug 2019
- First submitted
- 31 Aug 2016
- Last updated
- 6 Sep 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 32331936
Study at a glance
From the registry record, last updated by the sponsor on 6 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02890992
- Acronym / sponsor ID
- ODYSSEY KIDS / DFI14223
- Conditions
- Hypercholesterolaemia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 42 participants (actual)
- Lead sponsor
- SanofiIndustry (pharma, biotech, devices)
- Collaborators
- Regeneron Pharmaceuticals
- Study start
- 15 Sep 2016 (actual)
- Primary completion
- 13 Sep 2018 (actual)
- Study completion
- 22 Feb 2019 (actual)
- First posted
- 7 Sep 2016 (estimated)
- Results
- Posted 6 Sep 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 8
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 - Alirocumab 30 mg Q2W: <50 kg | Experimental | Drug: alirocumab SAR236553 (REGN727), Drug: statins, Drug: ezetimibe, Drug: cholestyramine, Drug: fenofibrate, Drug: omega-3 fatty acids, Drug: nicotinic acidPeriod 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. |
| Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg | Experimental | Drug: alirocumab SAR236553 (REGN727), Drug: statins, Drug: ezetimibe, Drug: cholestyramine, Drug: fenofibrate, Drug: omega-3 fatty acids, Drug: nicotinic acidPeriod 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. |
| Cohort 2 - Alirocumab 40 mg Q2W: <50 kg | Experimental | Drug: alirocumab SAR236553 (REGN727), Drug: statins, Drug: ezetimibe, Drug: cholestyramine, Drug: fenofibrate, Drug: omega-3 fatty acids, Drug: nicotinic acidPeriod 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. |
| Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg | Experimental | Drug: alirocumab SAR236553 (REGN727), Drug: statins, Drug: ezetimibe, Drug: cholestyramine, Drug: fenofibrate, Drug: omega-3 fatty acids, Drug: nicotinic acidPeriod 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. |
| Cohort 3 - Alirocumab 75 mg Q4W: <50 kg | Experimental | Drug: alirocumab SAR236553 (REGN727), Drug: statins, Drug: ezetimibe, Drug: cholestyramine, Drug: fenofibrate, Drug: omega-3 fatty acids, Drug: nicotinic acidPeriod 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. |
| Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg | Experimental | Drug: alirocumab SAR236553 (REGN727), Drug: statins, Drug: ezetimibe, Drug: cholestyramine, Drug: fenofibrate, Drug: omega-3 fatty acids, Drug: nicotinic acidPeriod 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. |
| Cohort 4 - Alirocumab 150 mg Q4W: <50 kg | Experimental | Drug: alirocumab SAR236553 (REGN727), Drug: statins, Drug: ezetimibe, Drug: cholestyramine, Drug: fenofibrate, Drug: omega-3 fatty acids, Drug: nicotinic acidPeriod 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. |
| Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg | Experimental | Drug: alirocumab SAR236553 (REGN727), Drug: statins, Drug: ezetimibe, Drug: cholestyramine, Drug: fenofibrate, Drug: omega-3 fatty acids, Drug: nicotinic acidPeriod 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. |
Who may qualify
- Ages
- 8 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| alirocumab SAR236553 (REGN727)Also: PraluentPharmaceutical form: solution Route of administration: subcutaneous injection | Drug | 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 150 mg Q4W: >=50 kg, Cohort 3 - Alirocumab 75 mg Q4W: <50 kg, Cohort 4 - Alirocumab 150 mg Q4W: <50 kg, Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg |
| statinsPharmaceutical form: tablet Route of administration: oral | Drug | 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 150 mg Q4W: >=50 kg, Cohort 3 - Alirocumab 75 mg Q4W: <50 kg, Cohort 4 - Alirocumab 150 mg Q4W: <50 kg, Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg |
| ezetimibePharmaceutical form:tablet Route of administration: oral | Drug | 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 150 mg Q4W: >=50 kg, Cohort 3 - Alirocumab 75 mg Q4W: <50 kg, Cohort 4 - Alirocumab 150 mg Q4W: <50 kg, Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg |
| cholestyraminePharmaceutical form:tablet Route of administration: oral | Drug | 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 150 mg Q4W: >=50 kg, Cohort 3 - Alirocumab 75 mg Q4W: <50 kg, Cohort 4 - Alirocumab 150 mg Q4W: <50 kg, Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg |
| fenofibratePharmaceutical form: tablet Route of administration: oral | Drug | 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 150 mg Q4W: >=50 kg, Cohort 3 - Alirocumab 75 mg Q4W: <50 kg, Cohort 4 - Alirocumab 150 mg Q4W: <50 kg, Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg |
| omega-3 fatty acidsPharmaceutical form: tablet Route of administration: oral | Drug | 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 150 mg Q4W: >=50 kg, Cohort 3 - Alirocumab 75 mg Q4W: <50 kg, Cohort 4 - Alirocumab 150 mg Q4W: <50 kg, Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg |
| nicotinic acidPharmaceutical form: tablet Route of administration: oral | Drug | 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 150 mg Q4W: >=50 kg, Cohort 3 - Alirocumab 75 mg Q4W: <50 kg, Cohort 4 - Alirocumab 150 mg Q4W: <50 kg, Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg |
Primary outcome
Percent Change From Baseline in Calculated Low Density Lipoprotein Cholesterol (LDL-C) at Week 8
Time frame: Baseline, 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.
19 secondary outcomes
Absolute Change From Baseline in Calculated Low Density Lipoprotein Cholesterol (LDL-C) at Week 8
Time frame: Baseline, Week 8
Percentage of Participants Achieving Calculated Low Density Lipoprotein Cholesterol (LDL-C) <130 mg/dL (3.37 mmol/L) at Week 8
Time frame: At Week 8
Percentage of Participants Achieving Calculated LDL-C <110 mg/dL (2.84 mmol/L) at Week 8
Time frame: At Week 8
Percent Change From Baseline in Calculated LDL-C at Week 12: Cohort 4
Time frame: Baseline, Week 12
Percent Change From Baseline in Apolipoprotein (Apo) B at Week 8
Time frame: Baseline, Week 8
Percent Change From Baseline in Non-High Density Lipoprotein (HDL-C) at Week 8
Time frame: Baseline, Week 8
Percent Change From Baseline in Total Cholesterol (Total-C) at Week 8
Time frame: Baseline, Week 8
Percent Change From Baseline in Lipoprotein(a) at Week 8
Time frame: Baseline, Week 8
Percent Change From Baseline in Fasting Triglyceride at Week 8
Time frame: Baseline, Week 8
Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at Week 8
Time frame: Baseline, Week 8
Percent Change From Baseline in Apolipoprotein A-1 at Week 8
Time frame: Baseline, Week 8
Absolute Change From Baseline in Apolipoprotein B at Week 8
Time frame: Baseline, Week 8
Absolute Change From Baseline in Non-High-Density Lipoprotein (Non-HDL-C) at Week 8
Time frame: Baseline, Week 8
Absolute Change From Baseline in Total Cholesterol (Total-C) at Week 8
Time frame: Baseline, Week 8
Absolute Change From Baseline in Lipoprotein(a) at Week 8
Time frame: Baseline, Week 8
Absolute Change From Baseline in HDL-C at Week 8
Time frame: Baseline, Week 8
Absolute Change From Baseline in Fasting Triglyceride at Week 8
Time frame: Baseline, Week 8
Absolute Change From Baseline in Apolipoprotein A-1 at Week 8
Time frame: Baseline, Week 8
Absolute Change From Baseline in Ratio Apolipoprotein B/Apolipoprotein A-1 at Week 8
Time frame: Baseline, Week 8
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Sep 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32331936Daniels 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Sciences & Operations study director
Sanofi
16 sites in 10 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing alirocumab SAR236553 (REGN727), statins and ezetimibe in people with Hypercholesterolaemia, run by Sanofi at 16 sites in 10 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 16 sites in United States, Czechia, Russia, Spain, Canada and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 Sep 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percent Change From Baseline in Calculated Low Density Lipoprotein Cholesterol (LDL-C) at Week 8 (time frame: Baseline, Week 8). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02890992, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Sep 2019; AzTrials last refreshed its copy on 27 Oct 2026.