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

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ClinicalTrials.gov Identifier: NCT02289963
Recruitment Status : Completed
First Posted : November 13, 2014
Results First Posted : June 26, 2017
Last Update Posted : June 26, 2017
Sponsor:
Collaborator:
Regeneron Pharmaceuticals
Information provided by (Responsible Party):
Sanofi

Tracking Information
First Submitted Date  ICMJE November 10, 2014
First Posted Date  ICMJE November 13, 2014
Results First Submitted Date  ICMJE April 24, 2017
Results First Posted Date  ICMJE June 26, 2017
Last Update Posted Date June 26, 2017
Study Start Date  ICMJE January 2015
Actual Primary Completion Date April 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 22, 2017)
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).
Original Primary Outcome Measures  ICMJE
 (submitted: November 10, 2014)
The percent change in calculated LDL-C from baseline to Week 24 in the intent-to-treat population [ Time Frame: From Baseline to Week 24 ]
Change History Complete list of historical versions of study NCT02289963 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 22, 2017)
  • 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).
  • 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.
  • 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).
  • 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.
  • 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).
  • 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.
  • 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).
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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).
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: November 10, 2014)
  • The percent change in calculated LDL-C in the modified intent-to-treat population [ Time Frame: From Baseline to Week 24 ]
  • The percent change in calculated low density lipoprotein cholesterol (LDL-C) [ Time Frame: From baseline to Week 12 ]
  • The percent change in apolipoprotein B (Apo B) [ Time Frame: From baseline to Week 24 and Week 12 ]
  • The percent change in non high density lipoprotein cholesterol (non-HDL-C) [ Time Frame: From baseline to Week 24 and Week 12 ]
  • The percent change in total cholesterol (TC) [ Time Frame: From baseline to Week 24 and Week 12 ]
  • The proportion of patients reaching calculated LDL-C <70 mg/dL (1.81 mmol/L) [ Time Frame: At Week 24 ]
  • The percent change in lipoprotein a (Lp [a]) [ Time Frame: From baseline to Week 24 and Week 12 ]
  • The percent change in high density lipoprotein cholesterol (HDL-C) [ Time Frame: From baseline to Week 24 and Week 12 ]
  • The percent change in fasting triglycerides (TGs) [ Time Frame: From baseline to Week 24 and Week 12 ]
  • The percent change in apolipoprotein A-1 (Apo A-1) [ Time Frame: From baseline to Week 24 and Week 12 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Evaluation of Alirocumab in Addition to Lipid-Modifying Therapy in Patients With High Cardiovascular Risk and Hypercholesterolemia in South Korea and Taiwan
Official Title  ICMJE 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
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).
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Hypercholesterolemia
Intervention  ICMJE
  • Drug: Placebo (for Alirocumab)
    Solution for injection, one subcutaneous injection in the abdomen with a disposable auto-injector.
  • 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.
Study Arms  ICMJE
  • Placebo Comparator: Placebo Q2W
    Placebo (for alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable Lipid-Modifying Therapy (LMT) for 24 weeks.
    Interventions:
    • Drug: Placebo (for Alirocumab)
    • Drug: Lipid-Modifying Therapy (LMT)
  • 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.
    Interventions:
    • Drug: Alirocumab
    • Drug: Lipid-Modifying Therapy (LMT)
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 18, 2016)
199
Original Estimated Enrollment  ICMJE
 (submitted: November 10, 2014)
184
Actual Study Completion Date  ICMJE April 2016
Actual Primary Completion Date April 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Korea, Republic of,   Taiwan
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02289963
Other Study ID Numbers  ICMJE EFC14074
U1111-1157-3294 ( Other Identifier: UTN )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Product Manufactured in and Exported from the U.S.: Yes
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Sanofi
Study Sponsor  ICMJE Sanofi
Collaborators  ICMJE Regeneron Pharmaceuticals
Investigators  ICMJE
Study Director: Clinical Sciences & Operations Sanofi
PRS Account Sanofi
Verification Date June 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP