Efficacy and Safety of Alirocumab in Patients With Hypercholesterolemia Not Adequately Controlled With Non-statin Lipid Modifying Therapy or the Lowest Strength of Statin

NCT ID: NCT02584504

Last Updated: 2019-01-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 163 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-11-30
• Study Completion Date: 2018-01-09

Brief Summary

Primary Objective:

To demonstrate the reduction of low-density lipoprotein cholesterol (LDL-C) by alirocumab administration as add-on therapy to non-statin lipid modifying therapy (LMT) including diet therapy alone or the lowest strength of statin in comparison with placebo after 12 weeks of treatment in participants with hypercholesterolemia.

Secondary Objective:

• To evaluate the effect of two treatment regimens 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), triglyceride (TG), and apolipoprotein A-1 (Apo A-1).
• To evaluate the safety and tolerability of alirocumab administration.
• To evaluate the development of anti-alirocumab antibodies.
• To evaluate the pharmacokinetic and pharmacodynamic profiles of alirocumab administration.
• To evaluate the long-term safety in participants receiving open-label alirocumab administration.

Detailed Description

The duration of study per participant was approximately 71 weeks consisting of a run-in period (4 weeks), a screening period (3 weeks), a double-blind treatment period (12 weeks), and an open-label treatment period (52 weeks).

Conditions

Hypercholesterolemia

Study Design

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

Study Groups

Alirocumab 150 mg Q4W

Double-blind treatment period(DBTP):participants received Alirocumab 150 mg subcutaneous injection every 4 week(Q4W) alternating with placebo(for alirocumab)Q4W added to lowest-strength statin therapy(atorvastatin 5 mg daily),stable non-statin LMT/diet therapy alone for 12weeks. Participants completed DBTP,entered open-label treatment period(OLTP),received alirocumab 150 mg Q4W up to additional 52 weeks. Alirocumab dose up-titrated to 150 mg every 2 weeks(Q2W) at Week 24(OLTP:Week 12),when targeted LDL-C level at Week 20 not achieved as Japan Atherosclerosis Society Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012:1) ≥100 mg/dL(2.59 mmol/L) in heterozygous familial hypercholesterolemia (heFH) participants/non-familial hypercholesterolemia (non-FH)participants with history of documented coronary heart disease;2) ≥120 mg/dL(3.10 mmol/L)in non-FH participants with history of documented diseases/other risk factors as categorized in primary prevention category III)

Group Type: EXPERIMENTAL

Alirocumab

Intervention Type: DRUG

Solution for injection, one subcutaneous injection in the abdomen, thigh, or outer area of upper arm with a disposable auto-injector.

Placebo

Intervention Type: DRUG

Solution for injection, one subcutaneous injection in the abdomen, thigh, or outer area of upper arm with a disposable auto-injector.

Atorvastatin

Intervention Type: DRUG

Atorvastatin 5 mg tablet orally.

Non-statin Lipid-Modifying Therapy

Intervention Type: DRUG

Ezetimibe, Bezafibrate or Fenofibrate at stable dose as background therapy.

Diet Alone

Intervention Type: OTHER

Stable cholesterol-lowering diet as background therapy.

Alirocumab 150 mg Q2W

In DBTP, participants received Alirocumab 150 mg subcutaneous (SC) injection Q2W added to lowest-strength statin therapy (atorvastatin 5 mg daily), stable non-statin LMT or diet therapy alone for 12 weeks. Participants who completed DBTP were entered in OLTP and received alirocumab 150 mg Q4W up to additional 52 weeks. Alirocumab dose up-titrated to 150 mg Q2W at Week 24 (Week 12 of OLTP), when targeted LDL-C levels at Week 20 were not achieved i.e. LDL-C ≥100 mg/dL (2.59 mmol/L) or ≥120 mg/dL (3.10 mmol/L) according to Japan Atherosclerosis Society(JAS) Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012.

Group Type: EXPERIMENTAL

Alirocumab

Intervention Type: DRUG

Solution for injection, one subcutaneous injection in the abdomen, thigh, or outer area of upper arm with a disposable auto-injector.

Atorvastatin

Intervention Type: DRUG

Atorvastatin 5 mg tablet orally.

Non-statin Lipid-Modifying Therapy

Intervention Type: DRUG

Ezetimibe, Bezafibrate or Fenofibrate at stable dose as background therapy.

Diet Alone

Intervention Type: OTHER

Stable cholesterol-lowering diet as background therapy.

Placebo Q2W

In DBTP, participants received Placebo (for alirocumab) SC injection Q2W added to lowest-strength statin therapy (atorvastatin 5 mg), stable non-statin LMT or diet therapy alone for 12 weeks. Participants who completed DBTP were entered in OLTP and received alirocumab 150 mg Q4W up to additional 52 weeks. Alirocumab dose up-titrated to 150 mg Q2W at Week 24 (Week 12 of OLTP), when targeted LDL-C levels at Week 20 were not achieved i.e. LDL-C ≥100 mg/dL (2.59 mmol/L) or ≥120 mg/dL (3.10 mmol/L) according to JAS Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Solution for injection, one subcutaneous injection in the abdomen, thigh, or outer area of upper arm with a disposable auto-injector.

Atorvastatin

Intervention Type: DRUG

Atorvastatin 5 mg tablet orally.

Non-statin Lipid-Modifying Therapy

Intervention Type: DRUG

Ezetimibe, Bezafibrate or Fenofibrate at stable dose as background therapy.

Diet Alone

Intervention Type: OTHER

Stable cholesterol-lowering diet as background therapy.

Interventions

Alirocumab

Solution for injection, one subcutaneous injection in the abdomen, thigh, or outer area of upper arm with a disposable auto-injector.

Intervention Type: DRUG

Placebo

Solution for injection, one subcutaneous injection in the abdomen, thigh, or outer area of upper arm with a disposable auto-injector.

Intervention Type: DRUG

Atorvastatin

Atorvastatin 5 mg tablet orally.

Intervention Type: DRUG

Non-statin Lipid-Modifying Therapy

Ezetimibe, Bezafibrate or Fenofibrate at stable dose as background therapy.

Intervention Type: DRUG

Diet Alone

Stable cholesterol-lowering diet as background therapy.

Intervention Type: OTHER

Other Intervention Names

SAR236553; REGN727

Eligibility Criteria

Inclusion Criteria

Participants with hypercholesterolemia (heFH or non-FH) receiving non statin LMTs or the lowest strength of statin.

Exclusion Criteria

• LDL-C <100 mg/dL (<2.59 mmol/L) at the screening visit (Week -3) in participants with heFH or in participants with non-FH who have a history of documented coronary heart disease.
• LDL-C <120 mg/dL (<3.10 mmol/L) at the screening visit (Week -3) in participants with non-FH participants who had a history of documented diseases or other risk factors classified as primary prevention category III as defined in JAS Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012.
• Not on a stable dose of LMT (including diet therapy alone) in the run-in period or the screening period.
• Fasting serum TGs >400 mg/dL (>4.52 mmol/L) at the screening period.
• Systolic blood pressure (BP) >160 mmHg or diastolic BP >100 mmHg at the run-in visit (Week -7) or the screening visit (Week -3) or the randomization visit (Week 0).

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

• Minimum Eligible Age: 20 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 392028

Ageo-Shi, , Japan

Investigational Site Number 392007

Chūōku, , Japan

Investigational Site Number 392029

Chūōku, , Japan

Investigational Site Number 392014

Fukui-shi, , Japan

Investigational Site Number 392023

Hachioji-Shi, , Japan

Investigational Site Number 392013

Itoshima-Shi, , Japan

Investigational Site Number 392010

Kanazawa, , Japan

Investigational Site Number 392024

Kasuga-Shi, , Japan

Investigational Site Number 392004

Kawanishi-Shi, , Japan

Investigational Site Number 392015

Kitakyushu-Shi, , Japan

Investigational Site Number 392005

Komatsu-Shi, , Japan

Investigational Site Number 392032

Matsudo-Shi, , Japan

Investigational Site Number 392017

Matsumoto-Shi, , Japan

Investigational Site Number 392003

Mito, , Japan

Investigational Site Number 392018

Morioka, , Japan

Investigational Site Number 392009

Moriya-Shi, , Japan

Investigational Site Number 392006

Nagoya, , Japan

Investigational Site Number 392011

Nagoya, , Japan

Investigational Site Number 392019

Nagoya, , Japan

Investigational Site Number 392025

Nagoya, , Japan

Investigational Site Number 392027

Osaka, , Japan

Investigational Site Number 392030

Sakura-Shi, , Japan

Investigational Site Number 392016

Shinagawa-Ku, , Japan

Investigational Site Number 392001

Shinjuku-Ku, , Japan

Investigational Site Number 392008

Shinjuku-Ku, , Japan

Investigational Site Number 392012

Shizuoka, , Japan

Investigational Site Number 392002

Suita-Shi, , Japan

Investigational Site Number 392031

Suita-Shi, , Japan

Investigational Site Number 392020

Toyonaka-Shi, , Japan

Investigational Site Number 392022

Yakushi, , Japan

Countries

Japan

References

Teramoto T, Kondo A, Kiyosue A, Harada-Shiba M, Ishigaki Y, Tobita K, Kawabata Y, Ozaki A, Baccara-Dinet MT, Sata M. Efficacy and safety of alirocumab in patients with hypercholesterolemia not adequately controlled with non-statin lipid-lowering therapy or the lowest strength of statin: ODYSSEY NIPPON study design and rationale. Lipids Health Dis. 2017 Jun 17;16(1):121. doi: 10.1186/s12944-017-0513-7.

Reference Type: BACKGROUND

PMID: 28623954 (View on PubMed)

Teramoto T, Kiyosue A, Ishigaki Y, Harada-Shiba M, Kawabata Y, Ozaki A, Baccara-Dinet MT, Sata M. Efficacy and safety of alirocumab 150mg every 4 weeks in hypercholesterolemic patients on non-statin lipid-lowering therapy or lowest strength dose of statin: ODYSSEY NIPPON. J Cardiol. 2019 Mar;73(3):218-227. doi: 10.1016/j.jjcc.2018.10.004. Epub 2018 Nov 30.

Reference Type: DERIVED

PMID: 30509509 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

U1111-1170-7697

Identifier Type: OTHER

Identifier Source: secondary_id

EFC14305

Identifier Type: -

Identifier Source: org_study_id