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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02023879




Registration number
NCT02023879
Ethics application status
Date submitted
6/12/2013
Date registered
30/12/2013
Date last updated
27/07/2018

Titles & IDs
Public title
Phase III Study To Evaluate Alirocumab in Patients With Hypercholesterolemia Not Treated With a Statin (ODYSSEY CHOICE II)
Scientific title
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study Evaluating the Efficacy and Safety of Alirocumab in Patients With Primary Hypercholesterolemia Not Treated With a Statin
Secondary ID [1] 0 0
2013-002659-14
Secondary ID [2] 0 0
EFC13786
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hypercholesterolemia 0 0
Condition category
Condition code
Metabolic and Endocrine 0 0 0 0
Other metabolic disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Alirocumab
Treatment: Drugs - Placebo (for Alirocumab)
Treatment: Drugs - Non-statin LMT
Other interventions - Diet Alone

Placebo comparator: Placebo Q2W - 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.

Other: Alirocumab 75 mg Q2W/Up to 150 mg Q2W (Calibrator) - 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.

Experimental: Alirocumab 150 mg Q4W/Up to 150 mg Q2W - 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.


Treatment: Drugs: Alirocumab
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).

Treatment: Drugs: Placebo (for Alirocumab)
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).

Treatment: Drugs: Non-statin LMT
Ezetimibe or Fenofibrate at stable dose as background therapy.

Other interventions: Diet Alone
Stable cholesterol-lowering diet as background therapy.
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent-to-Treat (ITT Analysis)
Timepoint [1] 0 0
From Baseline to Week 24
Secondary outcome [1] 0 0
Percent Change From Baseline in Calculated LDL-C at Week 24 - On-Treatment Analysis
Timepoint [1] 0 0
From Baseline to Week 24
Secondary outcome [2] 0 0
Percent Change From Baseline in Calculated LDL-C at Week 12 - ITT Analysis
Timepoint [2] 0 0
From Baseline to Week 24
Secondary outcome [3] 0 0
Percent Change From Baseline in Calculated LDL-C at Week 12 - On-Treatment Analysis
Timepoint [3] 0 0
From Baseline to Week 24
Secondary outcome [4] 0 0
Percent Change From Baseline in Calculated LDL-C to Averaged Weeks 9 to 12 - ITT- Analysis
Timepoint [4] 0 0
From Baseline to Week 24
Secondary outcome [5] 0 0
Percent Change From Baseline in Calculated LDL-C at Averaged Week 9 to 12 - On-Treatment Analysis
Timepoint [5] 0 0
From Baseline to Week 24
Secondary outcome [6] 0 0
Percent Change From Baseline in Apolipoprotein (Apo) B at Week 24 - ITT Analysis
Timepoint [6] 0 0
From Baseline to Week 24
Secondary outcome [7] 0 0
Percent Change From Baseline in Apo B at Week 24 - On-treatment Analysis
Timepoint [7] 0 0
From Baseline to Week 24
Secondary outcome [8] 0 0
Percent Change From Baseline in Non-HDL-C at Week 24 - ITT Analysis
Timepoint [8] 0 0
From Baseline to Week 24
Secondary outcome [9] 0 0
Percent Change From Baseline in Non-HDL-C at Week 24 - On-treatment Analysis
Timepoint [9] 0 0
From Baseline to Week 24
Secondary outcome [10] 0 0
Percent Change From Baseline in Total-C at Week 24 - ITT Analysis
Timepoint [10] 0 0
From Baseline to Week 24
Secondary outcome [11] 0 0
Percent Change From Baseline in Apo B at Week 12 - ITT Analysis
Timepoint [11] 0 0
From Baseline to Week 24
Secondary outcome [12] 0 0
Percent Change From Baseline in Non-HDL-C at Week 12 - ITT Analysis
Timepoint [12] 0 0
From Baseline to Week 24
Secondary outcome [13] 0 0
Percent Change From Baseline in Total-C at Week 12 - ITT Analysis
Timepoint [13] 0 0
From Baseline to Week 24
Secondary outcome [14] 0 0
Percentage of Very High Cardiovascular (CV) Risk Participants Achieving Calculated LDL-C <70 mg/dL (<1.81 mmol/L) or Moderate or High CV Risk Participants Achieving Calculated LDL-C <100 mg/dL (<2.59 mmol/L) at Week 24 - ITT Analysis
Timepoint [14] 0 0
From Baseline to Week 24
Secondary outcome [15] 0 0
Percentage of Very High CV Risk Participants Achieving Calculated LDL-C< 70 mg/dL (<1.81 mmol/L) or Moderate or High CV Risk Participants Achieving Calculated LDL-C< 100 mg/dL (<2.59 mmol/L) at Week 24 - On-treatment Analysis
Timepoint [15] 0 0
From Baseline to Week 24
Secondary outcome [16] 0 0
Percentage of Participants Achieving Calculated LDL-C< 70 mg/dL (<1.81 mmol/L) at Week 24 - ITT Analysis
Timepoint [16] 0 0
From Baseline to Week 24
Secondary outcome [17] 0 0
Percentage of Participants Achieving Calculated LDL-C <70 mg/dL (<1.81 mmol/L) at Week 24 - On-treatment Analysis
Timepoint [17] 0 0
From Baseline to Week 24
Secondary outcome [18] 0 0
Percent Change From Baseline in Lipoprotein (a) at Week 24 - ITT Analysis
Timepoint [18] 0 0
From Baseline to Week 24
Secondary outcome [19] 0 0
Percent Change From Baseline in Lipoprotein (a) at Week 12 - ITT Analysis
Timepoint [19] 0 0
From Baseline to Week 24
Secondary outcome [20] 0 0
Percent Change From Baseline in HDL-C at Week 24 - ITT Analysis
Timepoint [20] 0 0
From Baseline to Week 24
Secondary outcome [21] 0 0
Percent Change From Baseline in HDL-C at Week 12 - ITT Analysis
Timepoint [21] 0 0
From Baseline to Week 24
Secondary outcome [22] 0 0
Percent Change From Baseline in Fasting Triglycerides at Week 24 - ITT Analysis
Timepoint [22] 0 0
From Baseline to Week 24
Secondary outcome [23] 0 0
Percent Change From Baseline in Fasting Triglycerides at Week 12 - ITT Analysis
Timepoint [23] 0 0
From Baseline to Week 24
Secondary outcome [24] 0 0
Percent Change From Baseline in Apo A-1 at Week 24 - ITT Analysis
Timepoint [24] 0 0
From Baseline to Week 24
Secondary outcome [25] 0 0
Percent Change From Baseline in Apo A-1 at Week 12 - ITT Analysis
Timepoint [25] 0 0
From Baseline to Week 24

Eligibility
Key inclusion criteria
Inclusion criteria:

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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria:

* 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
16/12/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
30/06/2017
Sample size
Target
Accrual to date
Final
233
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Investigational Site Number 036703 - Ashford
Recruitment hospital [2] 0 0
Investigational Site Number 036702 - Perth
Recruitment hospital [3] 0 0
Investigational Site Number 036701 - Woolloongabba
Recruitment postcode(s) [1] 0 0
5035 - Ashford
Recruitment postcode(s) [2] 0 0
6000 - Perth
Recruitment postcode(s) [3] 0 0
4102 - Woolloongabba
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Massachusetts
Country [4] 0 0
United States of America
State/province [4] 0 0
Missouri
Country [5] 0 0
United States of America
State/province [5] 0 0
North Carolina
Country [6] 0 0
United States of America
State/province [6] 0 0
South Carolina
Country [7] 0 0
Belgium
State/province [7] 0 0
Antwerpen
Country [8] 0 0
Belgium
State/province [8] 0 0
Haine-Saint-Paul
Country [9] 0 0
Belgium
State/province [9] 0 0
Leuven
Country [10] 0 0
Canada
State/province [10] 0 0
Chicoutimi
Country [11] 0 0
Canada
State/province [11] 0 0
Quebec
Country [12] 0 0
Canada
State/province [12] 0 0
Sherbrooke
Country [13] 0 0
Canada
State/province [13] 0 0
Toronto
Country [14] 0 0
Canada
State/province [14] 0 0
Vancouver
Country [15] 0 0
Canada
State/province [15] 0 0
Victoria
Country [16] 0 0
Denmark
State/province [16] 0 0
Aarhus
Country [17] 0 0
Denmark
State/province [17] 0 0
Esbjerg
Country [18] 0 0
Denmark
State/province [18] 0 0
Glostrup
Country [19] 0 0
Denmark
State/province [19] 0 0
Hvidovre
Country [20] 0 0
Denmark
State/province [20] 0 0
Køge
Country [21] 0 0
Netherlands
State/province [21] 0 0
Amsterdam
Country [22] 0 0
Netherlands
State/province [22] 0 0
Den Helder
Country [23] 0 0
Netherlands
State/province [23] 0 0
Hoogeveen
Country [24] 0 0
Netherlands
State/province [24] 0 0
Hoorn
Country [25] 0 0
Netherlands
State/province [25] 0 0
Rotterdam
Country [26] 0 0
Netherlands
State/province [26] 0 0
Sneek
Country [27] 0 0
Netherlands
State/province [27] 0 0
Utrecht
Country [28] 0 0
Netherlands
State/province [28] 0 0
Venlo
Country [29] 0 0
New Zealand
State/province [29] 0 0
Auckland
Country [30] 0 0
New Zealand
State/province [30] 0 0
Christchurch
Country [31] 0 0
Spain
State/province [31] 0 0
A Coruna
Country [32] 0 0
Spain
State/province [32] 0 0
Barcelona
Country [33] 0 0
Spain
State/province [33] 0 0
Córdoba
Country [34] 0 0
Spain
State/province [34] 0 0
Granada
Country [35] 0 0
Spain
State/province [35] 0 0
Sant Joan Despí
Country [36] 0 0
Spain
State/province [36] 0 0
Santiago De Compostela
Country [37] 0 0
Spain
State/province [37] 0 0
Zaragoza

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Sanofi
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Regeneron Pharmaceuticals
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT02023879
Trial related presentations / publications
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.
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Sciences & Operations
Address 0 0
Sanofi
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT02023879