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Efficacy and Safety Evaluation of Alirocumab (SAR236553/REGN727) in Patients With Primary Hypercholesterolemia on Stable Atorvastatin Therapy in Japan

Primary Purpose

Hypercholesterolemia

Status

Completed

Phase

Phase 2

Locations

Japan

Study Type

Interventional

Intervention

Alirocumab

Placebo (for alirocumab)

Atorvastatin

About this trial

This is an interventional treatment trial for Hypercholesterolemia

Eligibility Criteria

20 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion criteria :

- Participants with primary hypercholesterolemia treated with atorvastatin at stable dose of 5-20 mg for at least 6 weeks prior to screening and likely to have LDL-C ≥100 mg/dL (≥2.59 mmol/L) at the screening visit.

- Participants with primary hypercholesterolemia who were receiving a lipid-lowering treatment other than atorvastatin, or who were not at stable dose of atorvastatin 5-20 mg for at least 6 weeks prior to screening if they were likely to have LDL-C ≥100 mg/dL (≥2.59 mmol/L) after a 6-week run-in treatment period on atorvastatin therapy.

Exclusion criteria:

LDL-C <100 mg/dL (<2.59 mmol/L)
- at screening visit for participants who were being treated with stable dose of atorvastatin 5-20 mg for at least 6 weeks prior to screening OR
- at the end of the 6-week run-in period on atorvastatin for participants receiving a lipid lowering treatment other than atorvastatin, or not at stable dose of atorvastatin 5-20 mg for at least 6 weeks prior to screening
Participants with type 1 diabetes
Participants with type 2 diabetes treated with insulin, or without, and considered poorly controlled at screening.

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

Sites / Locations

Investigational Site Number 392002
Investigational Site Number 392001
Investigational Site Number 392003
Investigational Site Number 392004

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Placebo Comparator

Experimental

Placebo Comparator

Arm Label

Placebo

Alirocumab 50 mg Q2W

Alirocumab 75 mg Q2W

Alirocumab 150 mg Q2W

Arm Description

Placebo (for alirocumab) every 2 weeks (Q2W) for 12-weeks in combination with atorvastatin stable dose.

Alirocumab 50 mg Q2W for 12-weeks in combination with atorvastatin stable dose.

Alirocumab 75 mg Q2W for 12-weeks in combination with atorvastatin stable dose.

Alirocumab 150 mg Q2W for 12-weeks in combination with atorvastatin stable dose.

Outcomes

Primary Outcome Measures

Percent Change From Baseline in Calculated LDL-C at Week 12 - On-Treatment Analysis

Calculated LDL-C values were obtained using the Friedewald formula. Baseline adjusted least squares (LS) means and standard errors were estimated using an analysis of covariance (ANCOVA) model including available post-baseline data on treatment from first investigational product (IP) injection up to 21 days after last IP injection (on-treatment analysis). Missing Week 12 data were imputed by last observation carried forward [LOCF] method.

Secondary Outcome Measures

Absolute Change From Baseline in Calculated LDL-C (mmol/L) at Week 12 - On-Treatment Analysis

Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.

Absolute Change From Baseline in Calculated LDL-C (mg/dL) at Week 12 - On-Treatment Analysis

Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.

Percentage of Participants Achieving Calculated LDL-C <100 mg/dL (2.59 mmol/L) and < 70 mg/dL (1.81 mmol/L) at Week 12 - On-Treatment Analysis

Percent Change From Baseline in Total Cholesterol, High-Density Lipoprotein Cholesterol (HDL-C), Non-HDL-C, and Apolipoprotein B (Apo-B) at Week 12 - On-Treatment Analysis

Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.

Percent Change From Baseline in Fasting Triglycerides and Lipoprotein (a) at Week 12 - On-Treatment Analysis

Since the assumptions of normal distribution and equality of variances were not verified for the lipid parameters, percent changes were expressed as median (inter-quartile range).

Absolute Change From Baseline in Apolipoprotein B/Apolipoprotein A-1 (ApoB/ApoA-1) Ratio at Week 12 - On-Treatment Analysis

Adjusted LS mean and standard errors were estimated using the same ANCOVA as for primary endpoint.

Full Information

NCT ID

NCT01812707

First Posted

March 14, 2013

Last Updated

September 27, 2016

Sponsor

Sanofi

Collaborators

Regeneron Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT01812707

Brief Title

Efficacy and Safety Evaluation of Alirocumab (SAR236553/REGN727) in Patients With Primary Hypercholesterolemia on Stable Atorvastatin Therapy in Japan

Official Title

A Multicenter, Randomized, Double-blind, Parallel-group, Placebo-controlled Study Evaluating the Efficacy and Safety of Three Doses of SAR236553 (REGN727) Over 12 Weeks in Patients With Primary Hypercholesterolemia and LDL-cholesterol ≥100 mg/dL (≥2.59 mmol/L) on Ongoing Stable Atorvastatin Therapy

Study Type

Interventional

2. Study Status

Record Verification Date

August 2015

Overall Recruitment Status

Completed

Study Start Date

March 2013 (undefined)

Primary Completion Date

January 2014 (Actual)

Study Completion Date

January 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Sanofi

Collaborators

Regeneron Pharmaceuticals

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

Alirocumab (SAR236553/REGN727) is a fully human monoclonal antibody that binds proprotein convertase subtilisin/kexin type 9 (PCSK9). Primary Objective of the study: To evaluate the effect of alirocumab on low-density lipoprotein cholesterol (LDL-C) levels after 12 weeks of treatment in comparison with placebo in participants with LDL-C ≥100 mg/dL (≥2.59 mmol/L) on ongoing stable atorvastatin therapy. Secondary Objectives: To evaluate the effects of alirocumab on other lipid levels after 12 weeks of treatment in comparison with placebo To evaluate the safety and tolerability of alirocumab To evaluate the development of anti-alirocumab antibodies To evaluate the pharmacokinetics of alirocumab

Detailed Description

The duration of study participation depended on the status of the participant at screening: 21 to 27 weeks including a screening/run-in period of 1 to 7 weeks, a double-blind treatment period of 12 weeks, followed by an 8-week follow-up period.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hypercholesterolemia

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

100 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Placebo (for alirocumab) every 2 weeks (Q2W) for 12-weeks in combination with atorvastatin stable dose.

Arm Title

Alirocumab 50 mg Q2W

Arm Type

Experimental

Arm Description

Alirocumab 50 mg Q2W for 12-weeks in combination with atorvastatin stable dose.

Arm Title

Alirocumab 75 mg Q2W

Arm Type

Experimental

Arm Description

Alirocumab 75 mg Q2W for 12-weeks in combination with atorvastatin stable dose.

Arm Title

Alirocumab 150 mg Q2W

Arm Type

Placebo Comparator

Arm Description

Alirocumab 150 mg Q2W for 12-weeks in combination with atorvastatin stable dose.

Intervention Type

Drug

Intervention Name(s)

Alirocumab

Other Intervention Name(s)

SAR236553, RGEN727

Intervention Description

Two SC injections in the abdomen only

Intervention Type

Drug

Intervention Name(s)

Placebo (for alirocumab)

Intervention Description

Two subcutaneous (SC) injections in the abdomen only Route of administration: subcutaneous injection (1 mL) in the abdomen

Intervention Type

Drug

Intervention Name(s)

Atorvastatin

Intervention Description

Orally once daily at a stable dose of 5 to 20 mg as background therapy Route of administration: oral administration in the evening

Primary Outcome Measure Information:

Title

Percent Change From Baseline in Calculated LDL-C at Week 12 - On-Treatment Analysis

Description

Time Frame

Baseline to Week 12 (LOCF)

Secondary Outcome Measure Information:

Title

Absolute Change From Baseline in Calculated LDL-C (mmol/L) at Week 12 - On-Treatment Analysis

Description

Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.

Time Frame

Baseline to Week 12 (LOCF)

Title

Absolute Change From Baseline in Calculated LDL-C (mg/dL) at Week 12 - On-Treatment Analysis

Description

Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.

Time Frame

Baseline to Week 12 (LOCF)

Title

Percentage of Participants Achieving Calculated LDL-C <100 mg/dL (2.59 mmol/L) and < 70 mg/dL (1.81 mmol/L) at Week 12 - On-Treatment Analysis

Time Frame

Week 12 (LOCF)

Title

Percent Change From Baseline in Total Cholesterol, High-Density Lipoprotein Cholesterol (HDL-C), Non-HDL-C, and Apolipoprotein B (Apo-B) at Week 12 - On-Treatment Analysis

Description

Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.

Time Frame

Baseline to Week 12 (LOCF)

Title

Percent Change From Baseline in Fasting Triglycerides and Lipoprotein (a) at Week 12 - On-Treatment Analysis

Description

Since the assumptions of normal distribution and equality of variances were not verified for the lipid parameters, percent changes were expressed as median (inter-quartile range).

Time Frame

Baseline to Week 12 (LOCF)

Title

Absolute Change From Baseline in Apolipoprotein B/Apolipoprotein A-1 (ApoB/ApoA-1) Ratio at Week 12 - On-Treatment Analysis

Description

Adjusted LS mean and standard errors were estimated using the same ANCOVA as for primary endpoint.

Time Frame

From Baseline to Week 12 (LOCF)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

20 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion criteria : - Participants with primary hypercholesterolemia treated with atorvastatin at stable dose of 5-20 mg for at least 6 weeks prior to screening and likely to have LDL-C ≥100 mg/dL (≥2.59 mmol/L) at the screening visit. OR - Participants with primary hypercholesterolemia who were receiving a lipid-lowering treatment other than atorvastatin, or who were not at stable dose of atorvastatin 5-20 mg for at least 6 weeks prior to screening if they were likely to have LDL-C ≥100 mg/dL (≥2.59 mmol/L) after a 6-week run-in treatment period on atorvastatin therapy. Exclusion criteria: LDL-C <100 mg/dL (<2.59 mmol/L) at screening visit for participants who were being treated with stable dose of atorvastatin 5-20 mg for at least 6 weeks prior to screening OR at the end of the 6-week run-in period on atorvastatin for participants receiving a lipid lowering treatment other than atorvastatin, or not at stable dose of atorvastatin 5-20 mg for at least 6 weeks prior to screening Participants with type 1 diabetes Participants with type 2 diabetes treated with insulin, or without, and considered poorly controlled at screening. The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Clinical Sciences & Operations

Organizational Affiliation

Sanofi

Official's Role

Study Director

Facility Information:

Facility Name

Investigational Site Number 392002

City

Koganei-Shi

Country

Japan

Facility Name

Investigational Site Number 392001

City

Shinjuku-Ku

Country

Japan

Facility Name

Investigational Site Number 392003

City

Suita-Shi

Country

Japan

Facility Name

Investigational Site Number 392004

City

Suita-Shi

Country

Japan

12. IPD Sharing Statement

Citations:

PubMed Identifier

27184170

Citation

Teramoto T, Kobayashi M, Uno K, Takagi Y, Matsuoka O, Sugimoto M, Inoue S, Minami F, Baccara-Dinet MT. Efficacy and Safety of Alirocumab in Japanese Subjects (Phase 1 and 2 Studies). Am J Cardiol. 2016 Jul 1;118(1):56-63. doi: 10.1016/j.amjcard.2016.04.011. Epub 2016 Apr 21.

Results Reference

result

PubMed Identifier

30183102

Citation

Leiter LA, Tinahones FJ, Karalis DG, Bujas-Bobanovic M, Letierce A, Mandel J, Samuel R, Jones PH. Alirocumab safety in people with and without diabetes mellitus: pooled data from 14 ODYSSEY trials. Diabet Med. 2018 Dec;35(12):1742-1751. doi: 10.1111/dme.13817. Epub 2018 Oct 9.

Results Reference

derived

Learn more about this trial

Efficacy and Safety Evaluation of Alirocumab (SAR236553/REGN727) in Patients With Primary Hypercholesterolemia on Stable Atorvastatin Therapy in Japan

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