Phase III Study To Evaluate Alirocumab in Patients With Hypercholesterolemia Not Treated With a Statin (ODYSSEY CHOICE II)

NCT02023879 | Completed Phase 3 Results DMC

• 3 other identifiers: EFC137862013-002659-14U1111-1146-3517
• Study Type: interventional
• Target: 233
• Locations: 8 countries
• Sites: 43

Brief Summary

Primary Objective: To demonstrate the reduction of low-density lipoprotein cholesterol (LDL-C) by a regimen of Alirocumab including a starting dose of 150 mg every 4 weeks (Q4W) as add-on to non-statin lipid modifying background therapy or as monotherapy in comparison with placebo in participants with primary hypercholesterolemia not treated with a statin. Secondary Objective:

• To evaluate the effects on other lipid parameters of Alirocumab 150 mg Q4W versus placebo.
• To evaluate the safety and tolerability of Alirocumab 150 mg Q4W. Alirocumab 75 mg Q2W was added as a calibrator arm.

Conditions

Hypercholesterolemia

Outcome Measures

Primary Outcomes (1)

• Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent-to-Treat (ITT Analysis)

  Adjusted Least-squares (LS) means and standard errors at Week 24 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 24 regardless of status on- or off-treatment were used in the model (ITT analysis).

  From Baseline to Week 24

Secondary Outcomes (25)

• Percent Change From Baseline in Calculated LDL-C at Week 24 - On-Treatment Analysis

  From Baseline to Week 24

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

  From Baseline to Week 24

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

  From Baseline to Week 24

• Percent Change From Baseline in Calculated LDL-C to Averaged Weeks 9 to 12 - ITT- Analysis

  From Baseline to Week 24

• Percent Change From Baseline in Calculated LDL-C at Averaged Week 9 to 12 - On-Treatment Analysis

  From Baseline to Week 24

Other Outcomes (1)

• Percent Change From Baseline in Calculated LDL-C at Week 32, 36, 48, 72, 96, 120, 144, 168 On-Treatment Analysis in Open Label Extension Treatment Phase

  Baseline, Week 32, 36, 48, 72, 96, 120, 144 and Week 168

Study Arms (3)

Placebo Q2W

PLACEBO COMPARATOR

Period 1: Placebo (for Alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable non-statin lipid modifying therapy (LMT) or diet alone for 24 weeks. Period 2: Alirocumab 150 mg SC injection every 4 weeks (Q4W) from Week 24 until second quarter 2017 or until the drug is commercially available in the country, whatever occurred first. Alirocumab dose could be either up-titrated to 150 mg Q2W from Week 36 or maintained according to the investigator judgement and low-density lipoprotein cholesterol (LDL-C) values. Subsequent down titration to 150 mg Q4W was allowed.

Drug: Alirocumab; Drug: Placebo (for Alirocumab); Drug: Non-statin LMT; Other: Diet Alone

Alirocumab 75 mg Q2W/Up to 150 mg Q2W (Calibrator)

OTHER

Period 1: Alirocumab 75 mg SC injection Q2W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted LDL-C levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or \<30% LDL-C reduction from baseline. Period 2: Alirocumab 150 mg SC injection Q4W from Week 24 until second quarter 2017 or until the drug is commercially available in the country, whatever occurred first. Alirocumab dose could be either up-titrated to 150 mg Q2W from Week 36 or maintained according to the investigator judgement and LDL-C values. Subsequent down titration to 150 mg Q4W was allowed.

Drug: Alirocumab; Drug: Non-statin LMT; Other: Diet Alone

Alirocumab 150 mg Q4W/Up to 150 mg Q2W

EXPERIMENTAL

Period 1: Alirocumab 150 mg SC injection Q4W alternating with placebo (for alirocumab) Q4W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted LDL-C levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or \<30% LDL-C reduction from baseline. Period 2: Alirocumab 150 mg SC injection Q4W from Week 24 until second quarter 2017 or until the drug is commercially available in the country, whatever occurred first. Alirocumab dose could be either up-titrated to 150 mg Q2W from Week 36 or maintained according to the investigator judgement and LDL-C values. Subsequent down titration to 150 mg Q4W was allowed.

Drug: Alirocumab; Drug: Placebo (for Alirocumab); Drug: Non-statin LMT; Other: Diet Alone

Interventions

Alirocumab DRUG

Solution for injection in the abdomen, thigh, or outer area of the upper arm by self-injection or by another designated person using auto-injector (also known as pre-filled pen).

Also known as: SAR236553, REGN727, Praluent®

Alirocumab 150 mg Q4W/Up to 150 mg Q2W; Alirocumab 75 mg Q2W/Up to 150 mg Q2W (Calibrator); Placebo Q2W

Placebo (for Alirocumab) DRUG

Solution for injection in the abdomen, thigh, or outer area of the upper arm by self-injection or by another designated person using auto-injector (also known as pre-filled pen).

Alirocumab 150 mg Q4W/Up to 150 mg Q2W; Placebo Q2W

Non-statin LMT DRUG

Ezetimibe or Fenofibrate at stable dose as background therapy.

Alirocumab 150 mg Q4W/Up to 150 mg Q2W; Alirocumab 75 mg Q2W/Up to 150 mg Q2W (Calibrator); Placebo Q2W

Diet Alone OTHER

Stable cholesterol-lowering diet as background therapy.

Alirocumab 150 mg Q4W/Up to 150 mg Q2W; Alirocumab 75 mg Q2W/Up to 150 mg Q2W (Calibrator); Placebo Q2W

Eligibility Criteria

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

You may qualify if:

• Participants with primary hypercholesterolemia (heterozygous familial hypercholesterolemia \[heFH\] or non-FH) not adequately controlled with their non-statin LMT (either ezetimibe or fenofibrate) or diet alone.

You may not qualify if:

• LDL-C \<70 mg/dL (1.81 mmol/L) at screening for statin intolerant participants at very high cardiovascular (CV) risk;
• LDL-C \<100 mg/dL (\<2.59 mmol/L) at screening for statin intolerant participants at high or moderate CV risk or, participants not fulfilling the statin intolerant definition at moderate CV risk;
• LDL-C ≥160 mg/dL (≥4.1 mmol/L) at screening for participants receiving diet only or, participants not fulfilling the statin intolerant definition at moderate CV risk and receiving a non-statin LMT.
• 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 (43)

Investigational Site Number 840703

Beverly Hills, California, 90211, United States

Location

Investigational Site Number 840704

Atlantis, Florida, 33462, United States

Location

Investigational Site Number 840708

Jacksonville, Florida, 32216, United States

Location

Investigational Site Number 840701

Sarasota, Florida, 34239, United States

Location

Investigational Site Number 840706

Fall River, Massachusetts, 02720, United States

Location

Investigational Site Number 840705

St Louis, Missouri, 63131, United States

Location

Investigational Site Number 840707

Durham, North Carolina, 27710, United States

Location

Investigational Site Number 840702

Summerville, South Carolina, 29485, United States

Location

Investigational Site Number 036703

Ashford, 5035, Australia

Location

Investigational Site Number 036702

Perth, 6000, Australia

Location

Investigational Site Number 036701

Woolloongabba, 4102, Australia

Location

Investigational Site Number 056702

Antwerp, 2060, Belgium

Location

Investigational Site Number 056703

Haine-Saint-Paul, 7100, Belgium

Location

Investigational Site Number 056701

Leuven, 3000, Belgium

Location

Investigational Site Number 124703

Chicoutimi, G7H 7P2, Canada

Location

Investigational Site Number 124701

Québec, G1V 4M6, Canada

Location

Investigational Site Number 124704

Sherbrooke, J1H 1Z1, Canada

Location

Investigational Site Number 124706

Toronto, M9V 4B4, Canada

Location

Investigational Site Number 124702

Vancouver, V5Z 1M9, Canada

Location

Investigational Site Number 124705

Victoria, V8T 5G4, Canada

Location

Investigational Site Number 208703

Aarhus, 8200, Denmark

Location

Investigational Site Number 208702

Esbjerg, 6700, Denmark

Location

Investigational Site Number 208701

Glostrup Municipality, 2600, Denmark

Location

Investigational Site Number 208704

Hvidovre, 2650, Denmark

Location

Investigational Site Number 208705

Køge, 4600, Denmark

Location

Investigational Site Number 528701

Amsterdam, 1105 AZ, Netherlands

Location

Investigational Site Number 528708

Den Helder, 1782 GZ, Netherlands

Location

Investigational Site Number 528702

Hoogeveen, 7909 AA, Netherlands

Location

Investigational Site Number 528703

Hoorn, 1625 HV, Netherlands

Location

Investigational Site Number 528706

Rotterdam, 3045 PM, Netherlands

Location

Investigational Site Number 528709

Sneek, 8601 ZK, Netherlands

Location

Investigational Site Number 528704

Utrecht, 3584 CX, Netherlands

Location

Investigational Site Number 528707

Venlo, 5912 BL, Netherlands

Location

Investigational Site Number 554702

Auckland, 1023, New Zealand

Location

Investigational Site Number 554701

Christchurch, 8011, New Zealand

Location

Investigational Site Number 724703

A Coruña, 15006, Spain

Location

Investigational Site Number 724707

Barcelona, 08025, Spain

Location

Investigational Site Number 724710

Barcelona, 08035, Spain

Location

Investigational Site Number 724702

Córdoba, 14004, Spain

Location

Investigational Site Number 724705

Granada, 18012, Spain

Location

Investigational Site Number 724709

Sant Joan Despí, 08970, Spain

Location

Investigational Site Number 724706

Santiago de Compostela, 15706, Spain

Location

Investigational Site Number 724701

Zaragoza, 50009, Spain

Location

Related Publications (1)

• Stroes E, Guyton JR, Lepor N, Civeira F, Gaudet D, Watts GF, Baccara-Dinet MT, Lecorps G, Manvelian G, Farnier M; ODYSSEY CHOICE II Investigators. Efficacy and Safety of Alirocumab 150 mg Every 4 Weeks in Patients With Hypercholesterolemia Not on Statin Therapy: The ODYSSEY CHOICE II Study. J Am Heart Assoc. 2016 Sep 13;5(9):e003421. doi: 10.1161/JAHA.116.003421.

  PMID: 27625344 RESULT

MeSH Terms

Conditions

Hypercholesterolemia

Interventions

alirocumab; Diet

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

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

Limitations and Caveats

The systematic randomization error was not anticipated to have an impact on the power of the study. The sample size to detect a difference in efficacy endpoints was reached (it was increased to obtain additional safety data) and blind was maintained.

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 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Masking during the double-blind treatment period
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: A double-blind treatment period of 24 weeks (3 parallel arms) followed by an open-label extension period (single arm)

Study Record Dates

• First Submitted: December 6, 2013
• First Posted: December 30, 2013
• Study Start: December 16, 2013
• Primary Completion: October 27, 2014
• Study Completion: June 30, 2017
• Last Updated: July 27, 2018
• Results First Posted: March 15, 2017

Record last verified: 2018-06

Locations

AU (3); BE (3); CA (6); NZ (2); DK (5); ES (8); US (8); NL (8)