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

NCT01812707 | Completed Phase 2 Results DMC

• 2 other identifiers: DFI12361U1111-1134-4749
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 4

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

Conditions

Hypercholesterolemia

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline to Week 12 (LOCF)

Secondary Outcomes (6)

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

  Baseline to Week 12 (LOCF)

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

  Baseline to Week 12 (LOCF)

• 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

  Week 12 (LOCF)

• 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

  Baseline to Week 12 (LOCF)

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

  Baseline to Week 12 (LOCF)

Study Arms (4)

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo (for alirocumab); Drug: Atorvastatin

Alirocumab 50 mg Q2W

EXPERIMENTAL

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

Drug: Alirocumab; Drug: Atorvastatin

Alirocumab 75 mg Q2W

EXPERIMENTAL

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

Drug: Alirocumab; Drug: Atorvastatin

Alirocumab 150 mg Q2W

PLACEBO COMPARATOR

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

Drug: Alirocumab; Drug: Atorvastatin

Interventions

Alirocumab DRUG

Two SC injections in the abdomen only

Also known as: SAR236553, RGEN727

Alirocumab 150 mg Q2W; Alirocumab 50 mg Q2W; Alirocumab 75 mg Q2W

Placebo (for alirocumab) DRUG

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

Placebo

Atorvastatin 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 50 mg Q2W; Alirocumab 75 mg Q2W; Placebo

Eligibility Criteria

• Age: 20 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \- 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sanofi: lead
• Regeneron Pharmaceuticals: collaborator

Study Sites (4)

Investigational Site Number 392002

Koganeishi, Japan

Location

Investigational Site Number 392001

Shinjuku-Ku, Japan

Location

Investigational Site Number 392003

Suita-Shi, Japan

Location

Investigational Site Number 392004

Suita-Shi, Japan

Location

Related Publications (2)

• 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.

  PMID: 27184170 RESULT

• 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.

  PMID: 30183102 DERIVED

MeSH Terms

Conditions

Hypercholesterolemia

Interventions

alirocumab; Atorvastatin

Condition Hierarchy (Ancestors)

Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi

Contact --US@sanofi.com

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 14, 2013
• First Posted: March 18, 2013
• Study Start: March 1, 2013
• Primary Completion: January 1, 2014
• Study Completion: January 1, 2014
• Last Updated: October 4, 2016
• Results First Posted: September 24, 2015

Record last verified: 2015-08

Locations

JP (4)