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

NCT ID: NCT01812707

Last Updated: 2016-10-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-03-31
• Study Completion Date: 2014-01-31

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.

Conditions

Hypercholesterolemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo (for alirocumab)

Intervention Type: DRUG

Two subcutaneous (SC) injections in the abdomen only

Route of administration: subcutaneous injection (1 mL) in the abdomen

Atorvastatin

Intervention Type: DRUG

Orally once daily at a stable dose of 5 to 20 mg as background therapy

Route of administration: oral administration in the evening

Alirocumab 50 mg Q2W

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

Group Type: EXPERIMENTAL

Alirocumab

Intervention Type: DRUG

Two SC injections in the abdomen only

Atorvastatin

Intervention Type: DRUG

Orally once daily at a stable dose of 5 to 20 mg as background therapy

Route of administration: oral administration in the evening

Alirocumab 75 mg Q2W

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

Group Type: EXPERIMENTAL

Alirocumab

Intervention Type: DRUG

Two SC injections in the abdomen only

Atorvastatin

Intervention Type: DRUG

Orally once daily at a stable dose of 5 to 20 mg as background therapy

Route of administration: oral administration in the evening

Alirocumab 150 mg Q2W

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

Group Type: PLACEBO_COMPARATOR

Alirocumab

Intervention Type: DRUG

Two SC injections in the abdomen only

Atorvastatin

Intervention Type: DRUG

Orally once daily at a stable dose of 5 to 20 mg as background therapy

Route of administration: oral administration in the evening

Interventions

Alirocumab

Two SC injections in the abdomen only

Intervention Type: DRUG

Placebo (for alirocumab)

Two subcutaneous (SC) injections in the abdomen only

Route of administration: subcutaneous injection (1 mL) in the abdomen

Intervention Type: DRUG

Atorvastatin

Orally once daily at a stable dose of 5 to 20 mg as background therapy

Route of administration: oral administration in the evening

Intervention Type: DRUG

Other Intervention Names

SAR236553; RGEN727

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

1. 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

2. Participants with type 1 diabetes

3. 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.

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Regeneron Pharmaceuticals

INDUSTRY

Sponsor Role: collaborator

Sanofi

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

Investigational Site Number 392002

Koganeishi, , Japan

Investigational Site Number 392001

Shinjuku-Ku, , Japan

Investigational Site Number 392003

Suita-Shi, , Japan

Investigational Site Number 392004

Suita-Shi, , Japan

Countries

Japan

References

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.

Reference Type: RESULT

PMID: 27184170 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 30183102 (View on PubMed)

Other Identifiers

U1111-1134-4749

Identifier Type: OTHER

Identifier Source: secondary_id

DFI12361

Identifier Type: -

Identifier Source: org_study_id