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

NCT02584504 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: EFC14305U1111-1170-7697
• Study Type: interventional
• Target: 163
• Locations: 1 country
• Sites: 30

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.

Conditions

Hypercholesterolemia

Keywords

Non-statin LMT; Low dose statin

Outcome Measures

Primary Outcomes (1)

• Percent Change From Baseline in Calculated LDL-C at Week 12- Intent to Treat (ITT) Analysis

  Adjusted Least-squares (LS) means and standard errors at Week 12 were obtained from a mixed-effect model with repeated measures (MMRM) to account for missing data. All available post-baseline data from Week 4 to Week 12 regardless of status on- or off-treatment were used in the model (ITT analysis).

  From Baseline to Week 12

Secondary Outcomes (14)

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

  From Baseline to Week 12

• Percent Change From Baseline in Calculated LDL-C to Averaged Week 10 to 12: ITT Analysis

  From Baseline to Week 12

• Percent Change From Baseline in Calculated LDL-C to Averaged Week 10 to 12- On-Treatment Analysis

  From Baseline to Week 12

• Percent Change From Baseline in Apolipoprotein B (Apo-B) at Week 12: ITT Analysis

  From Baseline to Week 12

• Percent Change From Baseline in Apo-B at Week 12- On-Treatment Analysis

  From Baseline to Week 12

Other Outcomes (1)

• Percent Change From Baseline in Calculated LDL-C at Week 20, 24, 36, 48 and 64 -OLTP Analysis

  Baseline, Weeks 20, 24, 36, 48 and 64

Study Arms (3)

Alirocumab 150 mg Q4W

EXPERIMENTAL

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)

Drug: Alirocumab; Drug: Placebo; Drug: Atorvastatin; Drug: Non-statin Lipid-Modifying Therapy; Other: Diet Alone

Alirocumab 150 mg Q2W

EXPERIMENTAL

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.

Drug: Alirocumab; Drug: Atorvastatin; Drug: Non-statin Lipid-Modifying Therapy; Other: Diet Alone

Placebo Q2W

PLACEBO COMPARATOR

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.

Drug: Placebo; Drug: Atorvastatin; Drug: Non-statin Lipid-Modifying Therapy; Other: Diet Alone

Interventions

Alirocumab DRUG

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

Also known as: SAR236553, REGN727

Alirocumab 150 mg Q2W; Alirocumab 150 mg Q4W

Placebo DRUG

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

Alirocumab 150 mg Q4W; Placebo Q2W

Atorvastatin DRUG

Atorvastatin 5 mg tablet orally.

Alirocumab 150 mg Q2W; Alirocumab 150 mg Q4W; Placebo Q2W

Non-statin Lipid-Modifying Therapy DRUG

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

Alirocumab 150 mg Q2W; Alirocumab 150 mg Q4W; Placebo Q2W

Diet Alone OTHER

Stable cholesterol-lowering diet as background therapy.

Alirocumab 150 mg Q2W; Alirocumab 150 mg Q4W; Placebo Q2W

Eligibility Criteria

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

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sanofi: lead
• Regeneron Pharmaceuticals: collaborator

Study Sites (30)

Investigational Site Number 392028

Ageo-Shi, Japan

Location

Investigational Site Number 392007

Chūōku, Japan

Location

Investigational Site Number 392029

Chūōku, Japan

Location

Investigational Site Number 392014

Fukui-shi, Japan

Location

Investigational Site Number 392023

Hachioji-Shi, Japan

Location

Investigational Site Number 392013

Itoshima-Shi, Japan

Location

Investigational Site Number 392010

Kanazawa, Japan

Location

Investigational Site Number 392024

Kasuga-Shi, Japan

Location

Investigational Site Number 392004

Kawanishi-Shi, Japan

Location

Investigational Site Number 392015

Kitakyushu-Shi, Japan

Location

Investigational Site Number 392005

Komatsu-Shi, Japan

Location

Investigational Site Number 392032

Matsudo-Shi, Japan

Location

Investigational Site Number 392017

Matsumoto-Shi, Japan

Location

Investigational Site Number 392003

Mito, Japan

Location

Investigational Site Number 392018

Morioka, Japan

Location

Investigational Site Number 392009

Moriya-Shi, Japan

Location

Investigational Site Number 392006

Nagoya, Japan

Location

Investigational Site Number 392011

Nagoya, Japan

Location

Investigational Site Number 392019

Nagoya, Japan

Location

Investigational Site Number 392025

Nagoya, Japan

Location

Investigational Site Number 392027

Osaka, Japan

Location

Investigational Site Number 392030

Sakura-Shi, Japan

Location

Investigational Site Number 392016

Shinagawa-Ku, Japan

Location

Investigational Site Number 392001

Shinjuku-Ku, Japan

Location

Investigational Site Number 392008

Shinjuku-Ku, Japan

Location

Investigational Site Number 392012

Shizuoka, Japan

Location

Investigational Site Number 392002

Suita-Shi, Japan

Location

Investigational Site Number 392031

Suita-Shi, Japan

Location

Investigational Site Number 392020

Toyonaka-Shi, Japan

Location

Investigational Site Number 392022

Yakushi, Japan

Location

Related Publications (2)

• 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.

  PMID: 28623954 BACKGROUND

• 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.

  PMID: 30509509 DERIVED

MeSH Terms

Conditions

Hypercholesterolemia

Interventions

alirocumab; Atorvastatin; Diet

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; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi

Contact-US@sanofi.com

800-633-1610

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 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 21, 2015
• First Posted: October 22, 2015
• Study Start: November 30, 2015
• Primary Completion: April 5, 2017
• Study Completion: January 9, 2018
• Last Updated: January 23, 2019
• Results First Posted: May 7, 2018

Record last verified: 2019-01

Locations

JP (30)