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

• Sponsor: Sanofi
• Collaborator: Regeneron Pharmaceuticals
• Information provided by (Responsible Party): Sanofi

Study Description

Brief 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).

Condition or disease	Intervention/treatment	Phase
Hypercholesterolemia	Drug: Placebo (for Alirocumab); Drug: Alirocumab; Drug: Lipid-Modifying Therapy (LMT)	Phase 3

Detailed 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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 199 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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
• Study Start Date: January 2015
• Actual Primary Completion Date: April 2016
• Actual Study Completion Date: April 2016

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Placebo Q2W; Placebo (for alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable Lipid-Modifying Therapy (LMT) for 24 weeks.	Drug: Placebo (for Alirocumab); Solution for injection, one subcutaneous injection in the abdomen with a disposable auto-injector.; Drug: Lipid-Modifying Therapy (LMT); Statins (Rosuvastatin, Simvastatin or Atorvastatin) at stable dose with or without other LMT as clinically indicated.
Placebo Comparator: Alirocumab 75 mg Q2W/Up to 150 mg Q2W; Alirocumab 75 mg SC injection Q2W added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Drug: Alirocumab; Solution for injection, one subcutaneous injection in the abdomen with a disposable auto-injector.; Other Names: SAR236553; REGN727; Praluent®; Drug: Lipid-Modifying Therapy (LMT); Statins (Rosuvastatin, Simvastatin or Atorvastatin) at stable dose with or without other LMT as clinically indicated.

Outcome Measures

Primary Outcome Measures :

1. Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent-to-Treat (ITT) Analysis [ Time Frame: From Baseline to Week 24 ]
   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).

Secondary Outcome Measures :

1. Percent Change From Baseline in Calculated LDL-C at Week 24 - On-Treatment Analysis [ Time Frame: From Baseline to Week 24 ]
   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).
2. Percent Change From Baseline in Calculated LDL-C at Week 12 - ITT Analysis [ Time Frame: From Baseline to Week 24 ]
   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.
3. Percent Change From Baseline in Calculated LDL-C at Week 12 - On-Treatment Analysis [ Time Frame: From Baseline to Week 24 ]
   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).
4. Percent Change From Baseline in Apolipoprotein (Apo) B at Week 24 - ITT Analysis [ Time Frame: From Baseline to Week 24 ]
   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.
5. Percent Change From Baseline in Apo B at Week 24 - On-treatment Analysis [ Time Frame: From Baseline to Week 24 ]
   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).
6. Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 24 - ITT Analysis [ Time Frame: From Baseline to Week 24 ]
   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.
7. Percent Change From Baseline in Non-HDL-C at Week 24 - On-treatment Analysis [ Time Frame: From Baseline to Week 24 ]
   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).
8. Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24 - ITT Analysis [ Time Frame: From Baseline to Week 24 ]
   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.
9. Percent Change From Baseline in Apo B at Week 12 - ITT Analysis [ Time Frame: From Baseline to Week 24 ]
   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.
10. Percent Change From Baseline in Non-HDL-C at Week 12 - ITT Analysis [ Time Frame: From Baseline to Week 24 ]
    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.
11. Percent Change From Baseline in Total-C at Week 12 - ITT Analysis [ Time Frame: From Baseline to Week 24 ]
    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.
12. Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - ITT Analysis [ Time Frame: From Baseline to Week 24 ]
    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.
13. Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - On-treatment Analysis [ Time Frame: From Baseline to Week 24 ]
    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).
14. Percent Change From Baseline in Lipoprotein(a) at Week 24 - ITT Analysis [ Time Frame: From Baseline to Week 24 ]
    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.
15. Percent Change From Baseline in High Density Lipoprotein (HDL-C) at Week 24 - ITT Analysis [ Time Frame: From Baseline to Week 24 ]
    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.
16. Percent Change From Baseline in Fasting Triglycerides at Week 24 - ITT Analysis [ Time Frame: From Baseline to Week 24 ]
    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.
17. Percent Change From Baseline in Apolipoprotein A-1 (Apo A-1) at Week 24 - ITT Analysis [ Time Frame: From Baseline to Week 24 ]
    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.
18. Percent Change From Baseline in Lipoprotein(a) at Week 12- ITT Analysis [ Time Frame: From Baseline to Week 24 ]
    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.
19. Percent Change From Baseline in HDL-C at Week 12 - ITT Analysis [ Time Frame: From Baseline to Week 24 ]
    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.
20. Percent Change From Baseline in Fasting Triglycerides at Week 12 - ITT Analysis [ Time Frame: From Baseline to Week 24 ]
    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.
21. Percent Change From Baseline in Apo A-1 at Week 12 - ITT Analysis [ Time Frame: From Baseline to Week 24 ]
    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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

Korea, Republic of

Investigational Site Number 410009

Anyang-Si, Korea, Republic of, 431-070

Investigational Site Number 410001

Anyang, Korea, Republic of, 431-070

Investigational Site Number 410017

Busan, Korea, Republic of, 602-715

Investigational Site Number 410007

Busan, Korea, Republic of, 614-735

Investigational Site Number 410002

Daegu, Korea, Republic of, 700-712

Investigational Site Number 410011

Goyang-Si, Korea, Republic of, 410-773

Investigational Site Number 410003

Gwangju, Korea, Republic of, 501-757

Investigational Site Number 410012

Incheon, Korea, Republic of, 405-760

Investigational Site Number 410018

Jeonju-Si, Korea, Republic of, 561-712

Investigational Site Number 410006

Seoul, Korea, Republic of, 06591

Investigational Site Number 410004

Seoul, Korea, Republic of, 07061

Investigational Site Number 410015

Seoul, Korea, Republic of, 08308

Investigational Site Number 410008

Seoul, Korea, Republic of, 110-746

Investigational Site Number 410005

Seoul, Korea, Republic of, 134-727

Investigational Site Number 410010

Seoul, Korea, Republic of, 152-703

Investigational Site Number 410013

Ulsan, Korea, Republic of

Taiwan

Investigational Site Number 158007

Changhua, Taiwan, 500

Investigational Site Number 158005

Hsinchu, Taiwan, 30071

Investigational Site Number 158011

Kaohsiung, Taiwan, 807

Investigational Site Number 158010

Kaohsiung, Taiwan, 833

Investigational Site Number 158006

Taichung, Taiwan

Investigational Site Number 158009

Tainan Hsien, Taiwan, 710

Investigational Site Number 158008

Tainan, Taiwan, 704

Investigational Site Number 158001

Taipei, Taiwan, 100

Investigational Site Number 158003

Taipei, Taiwan, 104

Investigational Site Number 158002

Taipei, Taiwan, 112

Investigational Site Number 158004

Taoyuan Hsien, Taiwan

Sponsors and Collaborators

Sanofi

Regeneron Pharmaceuticals

Investigators

• Study Director: Clinical Sciences & Operations; Sanofi

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Chao TH, Hsiao PJ, Liu ME, Wu CJ, Chiang FT, Chen ZC, Chen CP, Yeh HI, Lee TH, Chiang CE. A subanalysis of Taiwanese patients from ODYSSEY South Korea and Taiwan study evaluating the efficacy and safety of alirocumab. J Chin Med Assoc. 2019 Apr;82(4):265-271. doi: 10.1097/JCMA.0000000000000062.

Koh KK, Nam CW, Chao TH, Liu ME, Wu CJ, Kim DS, Kim CJ, Li I, Li J, Baccara-Dinet MT, Hsiao PJ, Chiang CE. A randomized trial evaluating the efficacy and safety of alirocumab in South Korea and Taiwan (ODYSSEY KT). J Clin Lipidol. 2018 Jan - Feb;12(1):162-172.e6. doi: 10.1016/j.jacl.2017.09.007. Epub 2017 Oct 19.

• Responsible Party: Sanofi
• ClinicalTrials.gov Identifier: NCT02289963 History of Changes
• Other Study ID Numbers: EFC14074; U1111-1157-3294 ( Other Identifier: UTN )
• First Posted: November 13, 2014
• Results First Posted: June 26, 2017
• Last Update Posted: June 26, 2017
• Last Verified: June 2017

• Studies a U.S. FDA-regulated Drug Product: Yes
• Product Manufactured in and Exported from the U.S.: Yes

Additional relevant MeSH terms:

Hypercholesterolemia; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Antibodies, Monoclonal; Immunologic Factors; Physiological Effects of Drugs