Evaluation of Alirocumab in Addition to Lipid-Modifying Therapy in Patients With High Cardiovascular Risk and Hypercholesterolemia in South Korea and Taiwan

Hypercholesterolemia Clinical Trial

Official title:

A Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study to Evaluate the Efficacy and Safety of Alirocumab in High Cardiovascular Risk Patients With Hypercholesterolemia Not Adequately Controlled With Their Lipid-Modifying Therapy in South Korea and Taiwan

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02289963
• Other study ID #: EFC14074
• Secondary ID: U1111-1157-3294
• Status: Completed
• Phase: Phase 3
• First received: November 10, 2014
• Last updated: June 22, 2017
• Start date: January 2015
• Est. completion date: April 2016

Study information

• Verified date: June 2017
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• 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 maximally tolerated daily statin therapy with or without other lipid-modifying therapy (LMT) in comparison with placebo after 24 weeks of treatment in high cardiovascular risk participants with hypercholesterolemia in South Korea and Taiwan.

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: apolipoprotein B (Apo B), non high-density lipoprotein cholesterol (non-HDL-C), total cholesterol (TC), lipoprotein (a) (Lp [a]), high-density lipoprotein cholesterol (HDL-C), triglycerides (TGs), and apolipoprotein A-1 (Apo A-1).

• To evaluate the safety and tolerability of alirocumab.

• To evaluate the development of anti-alirocumab antibodies (ADA).

Description:

The maximum study duration was approximately 35 weeks per participant, including up to 3 weeks screening period, 24 weeks double-blind treatment period, and 8 weeks follow-up period.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 199
• Est. completion date: April 2016
• Est. primary completion date: April 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion criteria:

Participants with hypercholesterolemia and established coronary heart disease (CHD) or CHD risk equivalents who are not adequately controlled with a maximally tolerated daily dose of statin with or without other LMT, both at stable dose for at least 4 weeks prior to screening visit (Week -3).

Exclusion criteria:

• Aged <18 years or legal age of adulthood, whichever was greater.

• Participants without established CHD or CHD risk equivalent.

• LDL-C <70 mg/dL (<1.81 mmol/L) in participants with a history of documented cardiovascular disease.

• LDL-C <100 mg/dL (<2.59 mmol/L) in participants without a history of documented cardiovascular disease.

• Not on a stable dose of LMT (including statin) for at least 4 weeks prior to the screening visit (Week -3) or between screening to randomization visits.

• Currently taking a statin other than atorvastatin, rosuvastatin or simvastatin.

• Atorvastatin, rosuvastatin or simvastatin was not taken daily or not taken at a registered dose.

• Daily doses above atorvastatin 80 mg, rosuvastatin 20 mg or simvastatin 40 mg.

• Fasting serum triglycerides >400 mg/dL (>4.52 mmol/L) at the screening period.

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

Related Conditions & MeSH terms

• Hypercholesterolemia

Intervention

Drug:
• Placebo (for Alirocumab)
Solution for injection, one subcutaneous injection in the abdomen with a disposable auto-injector.
• Alirocumab
Solution for injection, one subcutaneous injection in the abdomen with a disposable auto-injector.
• Lipid-Modifying Therapy (LMT)
Statins (Rosuvastatin, Simvastatin or Atorvastatin) at stable dose with or without other LMT as clinically indicated.

Locations

Country	Name	City	State
Korea, Republic of	Investigational Site Number 410001	Anyang
Korea, Republic of	Investigational Site Number 410009	Anyang-Si
Korea, Republic of	Investigational Site Number 410007	Busan
Korea, Republic of	Investigational Site Number 410017	Busan
Korea, Republic of	Investigational Site Number 410002	Daegu
Korea, Republic of	Investigational Site Number 410011	Goyang-Si
Korea, Republic of	Investigational Site Number 410003	Gwangju
Korea, Republic of	Investigational Site Number 410012	Incheon
Korea, Republic of	Investigational Site Number 410018	Jeonju-Si
Korea, Republic of	Investigational Site Number 410004	Seoul
Korea, Republic of	Investigational Site Number 410005	Seoul
Korea, Republic of	Investigational Site Number 410006	Seoul
Korea, Republic of	Investigational Site Number 410008	Seoul
Korea, Republic of	Investigational Site Number 410010	Seoul
Korea, Republic of	Investigational Site Number 410015	Seoul
Korea, Republic of	Investigational Site Number 410013	Ulsan
Taiwan	Investigational Site Number 158007	Changhua
Taiwan	Investigational Site Number 158005	Hsinchu
Taiwan	Investigational Site Number 158010	Kaohsiung
Taiwan	Investigational Site Number 158011	Kaohsiung
Taiwan	Investigational Site Number 158006	Taichung
Taiwan	Investigational Site Number 158008	Tainan
Taiwan	Investigational Site Number 158009	Tainan Hsien
Taiwan	Investigational Site Number 158001	Taipei
Taiwan	Investigational Site Number 158002	Taipei
Taiwan	Investigational Site Number 158003	Taipei
Taiwan	Investigational Site Number 158004	Taoyuan Hsien

Sponsors (2)

Lead Sponsor	Collaborator
Sanofi	Regeneron Pharmaceuticals

Countries where clinical trial is conducted

Korea, Republic of,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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 up to Week 24 regardless of status on- or off-treatment were used in the model (ITT analysis).	From Baseline to Week 24
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 up to Week 24 (i.e. up to 21 days after last injection) (on-treatment analysis).	From Baseline to Week 24
Secondary	Percent Change From Baseline in Calculated LDL-C at Week 12 - ITT Analysis	Adjusted LS means and standard errors at Week 12 were obtained from MMRM model including all available post-baseline data up to Week 24 regardless of status on- or off-treatment.	From Baseline to Week 24
Secondary	Percent Change From Baseline in Calculated LDL-C at Week 12 - On-Treatment Analysis	Adjusted LS means and standard errors at Week 12 were obtained from MMRM model including available post-baseline on-treatment data up to Week 24 (i.e. up to 21 days after last injection).	From Baseline to Week 24
Secondary	Percent Change From Baseline in Apolipoprotein (Apo) B at Week 24 - ITT Analysis	Adjusted LS means and standard errors at Week 24 were obtained from MMRM model including all available post-baseline data up to Week 24 regardless of status on- or off-treatment.	From Baseline to Week 24
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 up to Week 24 (i.e. up to 21 days after last injection).	From Baseline to Week 24
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 were obtained from MMRM model including all available post-baseline data up to Week 24 regardless of status on- or off-treatment.	From Baseline to Week 24
Secondary	Percent Change From Baseline in Non-HDL-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 up to Week 24 (i.e. up to 21 days after last injection).	From Baseline to Week 24
Secondary	Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24 - ITT Analysis	Adjusted LS means and standard errors at Week 24 were obtained from MMRM model including all available post-baseline data up to Week 24 regardless of status on- or off-treatment.	From Baseline to Week 24
Secondary	Percent Change From Baseline in Apo B at Week 12 - ITT Analysis	Adjusted LS means and standard errors at Week 12 were obtained from MMRM model including all available post-baseline data up to Week 24 regardless of status on- or off-treatment.	From Baseline to Week 24
Secondary	Percent Change From Baseline in Non-HDL-C at Week 12 - ITT Analysis	Adjusted LS means and standard errors at Week 12 were obtained from MMRM model including all available post-baseline data up to Week 24 regardless of status on- or off-treatment.	From Baseline to Week 24
Secondary	Percent Change From Baseline in Total-C at Week 12 - ITT Analysis	Adjusted LS means and standard errors at Week 12 were obtained from MMRM model including all available post-baseline data up to Week 24 regardless of status on- or off-treatment.	From Baseline to Week 24
Secondary	Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - ITT Analysis	Adjusted percentages at Week 24 were obtained from multiple imputation approach model for handling of missing data. All available post-baseline data up to Week 24 regardless of status on- or off-treatment were included in the imputation model.	From Baseline to Week 24
Secondary	Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - On-treatment Analysis	Adjusted percentages at Week 24 were obtained from multiple imputation approach model including available post-baseline on-treatment data up to Week 24 (i.e. up to 21 days after last injection).	From Baseline to Week 24
Secondary	Percent Change From Baseline in Lipoprotein(a) at Week 24 - ITT Analysis	Adjusted means and standard errors at Week 24 were obtained from multiple imputation approach followed by robust regression model for handling of missing data. All available post-baseline data up to Week 24 regardless of status on- or off-treatment were included in the imputation model.	From Baseline to Week 24
Secondary	Percent Change From Baseline in High Density Lipoprotein (HDL-C) at Week 24 - ITT Analysis	Adjusted LS means and standard errors at Week 24 were obtained from MMRM model including all available post-baseline data up to Week 24 regardless of status on- or off-treatment.	From Baseline to Week 24
Secondary	Percent Change From Baseline in Fasting Triglycerides at Week 24 - ITT Analysis	Adjusted means and standard errors at Week 24 were obtained from multiple imputation approach followed by robust regression model including all available post-baseline data up to Week 24 regardless of status on- or off-treatment.	From Baseline to Week 24
Secondary	Percent Change From Baseline in Apolipoprotein A-1 (Apo A-1) at Week 24 - ITT Analysis	Adjusted LS means and standard errors at Week 24 were obtained from MMRM model including all available post-baseline data up to Week 24 regardless of status on- or off-treatment.	From Baseline to Week 24
Secondary	Percent Change From Baseline in Lipoprotein(a) at Week 12- ITT Analysis	Adjusted means and standard errors at Week 12 were obtained from multiple imputation approach followed by robust regression model including all available post-baseline data up to Week 24 regardless of status on- or off-treatment.	From Baseline to Week 24
Secondary	Percent Change From Baseline in HDL-C at Week 12 - ITT Analysis	Adjusted LS means and standard errors at Week 12 were obtained from MMRM model including all available post-baseline data up to Week 24 regardless of status on- or off-treatment.	From Baseline to Week 24
Secondary	Percent Change From Baseline in Fasting Triglycerides at Week 12 - ITT Analysis	Adjusted means and standard errors at Week 12 were obtained from multiple imputation approach followed by a robust regression model including all available post-baseline data up to Week 24 regardless of status on- or off-treatment.	From Baseline to Week 24
Secondary	Percent Change From Baseline in Apo A-1 at Week 12 - ITT Analysis	Adjusted LS means and standard errors at Week 12 were obtained from MMRM model including all available post-baseline data up to Week 24 regardless of status on- or off-treatment.	From Baseline to Week 24