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

Hypercholesterolemia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01812707
• Other study ID #: DFI12361
• Secondary ID: U1111-1134-4749
• Status: Completed
• Phase: Phase 2
• First received: March 14, 2013
• Last updated: September 27, 2016
• Start date: March 2013
• Est. completion date: January 2014

Study information

• Verified date: August 2015
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: Japan: Pharmaceuticals and Medical Devices Agency
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: January 2014
• Est. primary completion date: January 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years to 75 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hypercholesterolemia

Intervention

Drug:
• Alirocumab
Two SC injections in the abdomen only
• Placebo (for alirocumab)
Two subcutaneous (SC) injections in the abdomen only Route of administration: subcutaneous injection (1 mL) in the abdomen
• Atorvastatin
Orally once daily at a stable dose of 5 to 20 mg as background therapy Route of administration: oral administration in the evening

Locations

Country	Name	City	State
Japan	Investigational Site Number 392002	Koganei-Shi
Japan	Investigational Site Number 392001	Shinjuku-Ku
Japan	Investigational Site Number 392003	Suita-Shi
Japan	Investigational Site Number 392004	Suita-Shi

Sponsors (2)

Lead Sponsor	Collaborator
Sanofi	Regeneron Pharmaceuticals

Country where clinical trial is conducted

Japan, 

References & Publications (1)

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.2016.04.01 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	No
Secondary	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.	Baseline to Week 12 (LOCF)	No
Secondary	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.	Baseline to Week 12 (LOCF)	No
Secondary	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)	No
Secondary	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.	Baseline to Week 12 (LOCF)	No
Secondary	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).	Baseline to Week 12 (LOCF)	No
Secondary	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.	From Baseline to Week 12 (LOCF)	No