Efficacy and Safety Evaluation of Alirocumab in Patients With Heterozygous Familial Hypercholesterolemia or High Cardiovascular Risk Patients With Hypercholesterolemia on Lipid Modifying Therapy (ODYSSEY JAPAN)

Hypercholesterolemia Clinical Trial

Official title:

A Randomized, Double-blind, Placebo-controlled, Parallel Group, Multicenter Study to Evaluate the Efficacy and Safety of Alirocumab in Heterozygous Familial Hypercholesterolemia or High Cardiovascular Risk Patients With Hypercholesterolemia Not Adequately Controlled With Their Lipid Modifying Therapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02107898
• Other study ID #: EFC13672
• Secondary ID: U1111-1115-7486
• Status: Completed
• Phase: Phase 3
• First received: April 4, 2014
• Last updated: September 27, 2016
• Start date: March 2014
• Est. completion date: September 2015

Study information

• Verified date: September 2016
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: Japan: Ministry of Health, Labor and Welfare
• Study type: Interventional

Clinical Trial Summary

Primary Objective:

To demonstrate the reduction of low-density lipoprotein cholesterol (LDL-C) by alirocumab as add-on therapy to stable daily statin therapy with or without other lipid modifying therapy in comparison with placebo after 24 weeks of treatment in heterozygous familial hypercholesterolemia (HeFH) or high cardiovascular risk participants with hypercholesterolemia.

Secondary Objectives:

• To evaluate the effect of alirocumab in comparison with placebo on LDL-C after 12 weeks of treatment.

• To evaluate the effect of alirocumab on other lipid parameters.

• To evaluate the long-term effect of alirocumab in comparison with placebo on LDL-C after 52 weeks of treatment.

• To evaluate the safety and tolerability of alirocumab.

• To evaluate the development of anti-alirocumab antibodies.

• To evaluate the pharmacokinetics of alirocumab.

Description:

Total duration per participant of approximately 63 weeks (14 months) (screening: 3 weeks, double-blind treatment period: 52 weeks, and follow-up period: 8 weeks).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 216
• Est. completion date: September 2015
• Est. primary completion date: January 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years to 80 Years

Eligibility

Inclusion criteria:

Participants with heterozygous familial hypercholesterolemia or non-familial hypercholesterolemia who were not adequately controlled with a stable daily dose of statin with or without other lipid modifying therapy, at stable dose prior to the screening visit (Week -3).

Exclusion criteria:

1. LDL-C <100 mg/dL (<2.59 mmol/L) at the screening visit in participants with heterozygous familial hypercholesterolemia or in participants with non-familial hypercholesterolemia who had a history of documented coronary heart disease as described in Japan Atherosclerosis Society (JAS) Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012.

2. LDL-C <120 mg/dL (<3.10 mmol/L) at the screening visit in participants with non-familial hypercholesterolemia who had a history of documented diseases or other risk factors as categorized in primary prevention category III as described in JAS Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012.

3. Not on a stable daily dose of lipid modifying therapy (including statin) within 4 weeks prior to the screening visit or between screening and randomization visits.

4. Age <20 years at the screening visit.

The above information is not intended to contain all considerations relevant to a participants' potential participation in a clinical trial.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hypercholesterolemia
• Hyperlipoproteinemia Type II

Intervention

Drug:
• Placebo (for alirocumab)
Solution for injection, one subcutaneous injection in the abdomen, thigh, or outer area of upper arm with an auto-injector.
• Alirocumab
Solution for injection, one subcutaneous injection in the abdomen, thigh, or outer area of upper arm with an auto-injector.
• Lipid-Modifying Therapy (LMT)
Statin (pravastatin, simvastatin, fluvastatin, atorvastatin, pitavastatin, rosuvastatin) at stable dose with or without other LMT as clinically indicated.

Locations

Country	Name	City	State
Japan	Investigational Site Number 392016	Adachi-Ku
Japan	Investigational Site Number 392029	Adachi-Ku
Japan	Investigational Site Number 392024	Aki-Gun
Japan	Investigational Site Number 392012	Chuo-Ku
Japan	Investigational Site Number 392013	Chuo-Ku
Japan	Investigational Site Number 392032	Fukui-Shi
Japan	Investigational Site Number 392004	Hakusan-Shi
Japan	Investigational Site Number 392028	Kaga-Shi
Japan	Investigational Site Number 392002	Kanazawa-Shi
Japan	Investigational Site Number 392005	Kanazawa-Shi
Japan	Investigational Site Number 392023	Kawanishi-Shi
Japan	Investigational Site Number 392009	Kisarazu-Shi
Japan	Investigational Site Number 392026	Kitakyushu-Shi
Japan	Investigational Site Number 392003	Komatsu-Shi
Japan	Investigational Site Number 392011	Kuki-Shi
Japan	Investigational Site Number 392017	Matsumoto-Shi
Japan	Investigational Site Number 392007	Mito-Shi
Japan	Investigational Site Number 392006	Moriya-Shi
Japan	Investigational Site Number 392018	Nagoya-Shi
Japan	Investigational Site Number 392014	Oota-Ku
Japan	Investigational Site Number 392019	Osaka-Shi
Japan	Investigational Site Number 392020	Osaka-Shi
Japan	Investigational Site Number 392022	Osaka-Shi
Japan	Investigational Site Number 392030	Osaka-Shi
Japan	Investigational Site Number 392027	Oyabe-Shi
Japan	Investigational Site Number 392010	Saitama-Shi
Japan	Investigational Site Number 392015	Shinjuku-Ku
Japan	Investigational Site Number 392031	Shizuoka-Shi
Japan	Investigational Site Number 392021	Suita-Shi
Japan	Investigational Site Number 392025	Takamatsu-Shi
Japan	Investigational Site Number 392008	Tsuchiura-Shi
Japan	Investigational Site Number 392001	Yamagata-Shi

Sponsors (2)

Lead Sponsor	Collaborator
Sanofi	Regeneron Pharmaceuticals

Country where clinical trial is conducted

Japan, 

References & Publications (1)

Teramoto T, Kobayashi M, Tasaki H, Yagyu H, Higashikata T, Takagi Y, Uno K, Baccara-Dinet MT, Nohara A. Efficacy and Safety of Alirocumab in Japanese Patients With Heterozygous Familial Hypercholesterolemia or at High Cardiovascular Risk With Hypercholest — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Percent Change From Baseline in Calculated LDL-C at Week 52 - ITT Analysis	Adjusted LS means and standard errors at Week 52 from MMRM model including available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.	From Baseline to Week 52	No
Other	Percent Change From Baseline in Calculated LDL-C at Week 52 - On-Treatment Analysis	Adjusted LS means and standard errors at Week 52 were obtained from MMRM model including available post-baseline on-treatment data from Week 4 to Week 52 (i.e. up to 21 days after last injection).	From Baseline to Week 52	No
Primary	Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent-to-Treat (ITT Analysis)	Adjusted least-squares (LS) means and standard errors at Week 24 were obtained from a mixed-effect model with repeated measures (MMRM) to account for missing data. All available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment were used in the model (ITT analysis).	From Baseline to Week 24	No
Secondary	Percent Change From Baseline in Calculated LDL-C at Week 24 - On-Treatment Analysis	Adjusted LS means and standard errors at Week 24 were obtained from MMRM model including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection) (on-treatment analysis).	From Baseline to Week 24	No
Secondary	Percent Change From Baseline in Calculated LDL-C at Week 12 - ITT Analysis	Adjusted LS means and standard errors at Week 12 from MMRM model including available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.	From Baseline to Week 24	No
Secondary	Percent Change From Baseline in Calculated LDL-C at Week 12 - On-treatment Analysis	Adjusted LS means and standard errors at Week 12 from MMRM model including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection).	From Baseline to Week 24	No
Secondary	Percent Change From Baseline in Apolipoprotein (Apo) B at Week 24 - ITT Analysis	Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.	From baseline to Week 24	No
Secondary	Percent Change From Baseline in Apo B at Week 24 - On-Treatment Analysis	Adjusted LS means and standard errors at Week 24 were obtained from MMRM model including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection).	From Baseline to Week 24	No
Secondary	Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 24 - ITT Analysis	Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.	From Baseline to Week 24	No
Secondary	Percent Change From Baseline in Non-HDL-C at Week 24 - On-Treatment Analysis	Adjusted LS means and standard errors at Week 24 from MMRM model including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection).	From Baseline to Week 24	No
Secondary	Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24 - ITT Analysis	Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.	From Baseline to Week 24	No
Secondary	Percent Change From Baseline in Apo B at Week 12 - ITT Analysis	Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.	From Baseline to Week 24	No
Secondary	Percent Change From Baseline in Non-HDL-C at Week 12 - ITT Analysis	Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.	From Baseline to Week 24	No
Secondary	Percent Change From Baseline in Total-C at Week 12 - ITT Analysis	Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.	From Baseline to Week 24	No
Secondary	Percentage of Participants Reaching Calculated LDL-C Goal at Week 24 - ITT Analysis	Calculated LDL-C goal was defined as: <100 mg/dL (2.59 mmol/L) for heFH or non-FH participants who had a history of documented congestive heart disease (CHD), or; <120 mg/dL (3.10 mmol/L) for non-FH participants who had a history of documented diseases (ischemic stroke, peripheral artery disease, chronic kidney disease or diabetes) or other risk factors as defined in JAS Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012.; Adjusted percentages at Week 24 were obtained from multiple imputation approach model for handling of missing data. All available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment were included in imputation model.	Up to Week 24	No
Secondary	Percentage of Participants Reaching Calculated LDL-C Goal at Week 24 - On-Treatment Analysis	Adjusted percentages at Week 24 were from multiple imputation approach model including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection).	Up to Week 24	No
Secondary	Percent Change From Baseline in Lipoprotein (a) at Week 24 - ITT Analysis	Adjusted means and standard errors at Week 24 from a multiple imputation approach followed by robust regression model for handling of missing data. All available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment were included in the imputation model.	From Baseline to Week 24	No
Secondary	Percent Change From Baseline in Fasting Triglycerides at Week 24 - ITT Analysis	Adjusted means and standard errors at Week 24 from multiple imputation approach followed by robust regression model including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment.	From Baseline to Week 24	No
Secondary	Percent Change From Baseline in HDL-C at Week 24 - ITT Analysis	Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.	From Baseline to Week 24	No
Secondary	Percent Change From Baseline in Apo A1 at Week 24 - ITT Analysis	Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.	From Baseline to Week 24	No
Secondary	Percent Change From Baseline in Lipoprotein (a) at Week 12 - ITT Analysis	Adjusted means and standard errors at Week 12 from multiple imputation approach followed by robust regression model including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment.	From Baseline to Week 24	No
Secondary	Percent Change From Baseline in Fasting Triglycerides at Week 12 - ITT Analysis	Adjusted means and standard errors at Week 12 from multiple imputation approach followed by robust regression model including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment.	From Baseline to Week 24	No
Secondary	Percent Change From Baseline in HDL-C at Week 12 - ITT Analysis	Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.	From Baseline to Week 24	No
Secondary	Percent Change From Baseline in Apo A1 at Week 12 - ITT Analysis	Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.	From Baseline to Week 24	No