HypercholesterolemiaPhase 3NCT02023879

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

A Phase 3 study testing Alirocumab, Non-statin LMT and Diet Alone in people with Hypercholesterolemia, run by Sanofi at 43 sites in 8 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial 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… Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Hypercholesterolemia
What is being tested?: Alirocumab, Non-statin LMT and Diet Alone
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 233 participants
Where: 43 sitesin 8 countries
Study dates: 16 Dec 2013to 30 Jun 2017
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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.

Trial locations and contacts

43 sites in 8 countries.

Country

City, postcode or hospital

43 sites in 8 countries

United States8 sites

Investigational Site Number 840704
Atlantis, Florida, 33462
Investigational Site Number 840703
Beverly Hills, California, 90211
Investigational Site Number 840707
Durham, North Carolina, 27710
Investigational Site Number 840706
Fall River, Massachusetts, 02720
Investigational Site Number 840708
Jacksonville, Florida, 32216
Investigational Site Number 840701
Sarasota, Florida, 34239
Investigational Site Number 840705
St Louis, Missouri, 63131
Investigational Site Number 840702
Summerville, South Carolina, 29485

Other trials in United States

Netherlands8 sites

Investigational Site Number 528701
Amsterdam, 1105 AZ
Investigational Site Number 528708
Den Helder, 1782 GZ
Investigational Site Number 528702
Hoogeveen, 7909 AA
Investigational Site Number 528703
Hoorn, 1625 HV
Investigational Site Number 528706
Rotterdam, 3045 PM
Investigational Site Number 528709
Sneek, 8601 ZK
Investigational Site Number 528704
Utrecht, 3584 CX
Investigational Site Number 528707
Venlo, 5912 BL

Other trials in Netherlands

Spain8 sites

Investigational Site Number 724703
A Coruña, 15006
Investigational Site Number 724707
Barcelona, 08025
Investigational Site Number 724710
Barcelona, 08035
Investigational Site Number 724702
Córdoba, 14004
Investigational Site Number 724705
Granada, 18012
Investigational Site Number 724709
Sant Joan Despí, 08970
Investigational Site Number 724706
Santiago de Compostela, 15706
Investigational Site Number 724701
Zaragoza, 50009

Other trials in Spain

Canada6 sites

Investigational Site Number 124703
Chicoutimi, G7H 7P2
Investigational Site Number 124701
Québec, G1V 4M6
Investigational Site Number 124704
Sherbrooke, J1H 1Z1
Investigational Site Number 124706
Toronto, M9V 4B4
Investigational Site Number 124702
Vancouver, V5Z 1M9
Investigational Site Number 124705
Victoria, V8T 5G4

Other trials in Canada

Denmark5 sites

Investigational Site Number 208703
Aarhus, 8200
Investigational Site Number 208702
Esbjerg, 6700
Investigational Site Number 208701
Glostrup Municipality, 2600
Investigational Site Number 208704
Hvidovre, 2650
Investigational Site Number 208705
Køge, 4600

Other trials in Denmark

Australia3 sites

Investigational Site Number 036703
Ashford, 5035
Investigational Site Number 036702
Perth, 6000
Investigational Site Number 036701
Woolloongabba, 4102

Other trials in Australia

Belgium3 sites

Investigational Site Number 056702
Antwerp, 2060
Investigational Site Number 056703
Haine-Saint-Paul, 7100
Investigational Site Number 056701
Leuven, 3000

Other trials in Belgium

New Zealand2 sites

Investigational Site Number 554702
Auckland, 1023
Investigational Site Number 554701
Christchurch, 8011

Other trials in New Zealand

About this study

Official 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

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.

Read the detailed description

The core study duration was approximately 35 weeks per participant (screening: 3 weeks, double-blind treatment period: 24 weeks; follow-up: 8 weeks). Participants who successfully completed the treatment period had the possibility to participate in an optional open-label treatment period with Alirocumab 150 mg Q4W until second quarter 2017 or until the drug is commercially available in the country, whatever occurred first.

Conditions: Hypercholesterolemia
Being tested: Alirocumab, Placebo (for Alirocumab), Non-statin LMT, Diet Alone
Medical subject headings: Hypercholesterolemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

AlirocumabDrug
Also called SAR236553, REGN727, Praluent®
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).
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).
Non-statin LMTDrug
Ezetimibe or Fenofibrate at stable dose as background therapy.
Diet AloneOther
Stable cholesterol-lowering diet as background therapy.

Study groups in NCT02023879
Study group	Role	What they receive
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. Receives: 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. Receives: 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. Receives: Drug: Alirocumab; Drug: Placebo (for Alirocumab); Drug: Non-statin LMT; Other: Diet Alone

What is being measured

The primary outcome is the main question the study is designed to answer.

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).
Measured: From Baseline to Week 24

Secondary outcomes (25)

Percent Change From Baseline in Calculated LDL-C at Week 24 - On-Treatment Analysis
Adjusted LS means and standard errors at Week 24 from MMRM model including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection) (on-treatment analysis).
Measured: From Baseline to Week 24
Percent Change From Baseline in Calculated LDL-C at Week 12 - ITT Analysis
Adjusted LS means and standard errors at Week 12 from MMRM including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment.
Measured: From Baseline to Week 24
Percent Change From Baseline in Calculated LDL-C at Week 12 - On-Treatment Analysis
Adjusted LS means and standard errors at Week 12 from MMRM model including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection).
Measured: From Baseline to Week 24
Percent Change From Baseline in Calculated LDL-C to Averaged Weeks 9 to 12 - ITT- Analysis
Adjusted LS means and standard errors at Week 12 from MMRM including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment and assigning a weight of 0.25 for Week 9, 10, 11 and 12 time points.
Measured: From Baseline to Week 24
Percent Change From Baseline in Calculated LDL-C at Averaged Week 9 to 12 - On-Treatment Analysis
Adjusted LS means and standard errors at Week 12 from MMRM model including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection) and assigning a weight of 0.25 for Week 9, 10, 11 and 12 time points.
Measured: From Baseline to Week 24
Percent Change From Baseline in Apolipoprotein (Apo) B at Week 24 - ITT Analysis
Adjusted LS means and standard errors at Week 24 from MMRM including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment.
Measured: From Baseline to Week 24
Percent Change From Baseline in Apo B at Week 24 - On-treatment Analysis
Adjusted LS means and standard errors at Week 24 from MMRM model including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection).
Measured: From Baseline to Week 24
Percent Change From Baseline in Non-HDL-C at Week 24 - ITT Analysis
Adjusted LS means and standard errors at Week 24 from MMRM including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment.
Measured: From Baseline to Week 24
Percent Change From Baseline in Non-HDL-C at Week 24 - On-treatment Analysis
Adjusted LS means and standard errors at Week 24 from MMRM model including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection).
Measured: From Baseline to Week 24
Percent Change From Baseline in Total-C at Week 24 - ITT Analysis
Adjusted LS means and standard errors at Week 24 from MMRM including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment.
Measured: From Baseline to Week 24
Percent Change From Baseline in Apo B at Week 12 - ITT Analysis
Adjusted LS means and standard errors at Week 12 from MMRM including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment.
Measured: From Baseline to Week 24
Percent Change From Baseline in Non-HDL-C at Week 12 - ITT Analysis
Adjusted LS means and standard errors at Week 12 from MMRM including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment.
Measured: From Baseline to Week 24
Percent Change From Baseline in Total-C at Week 12 - ITT Analysis
Adjusted LS means and standard errors at Week 12 from MMRM including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment.
Measured: From Baseline to Week 24
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
Moderate CV risk: 10-year fatal cardiovascular disease (CVD) risk Systemic Coronary Risk Evaluation (SCORE) ≥1 and <5%.
High CV risk: 10-year fatal CVD risk SCORE ≥5% or moderate chronic kidney disease or type 1 or type 2 diabetes mellitus without target organ damage or familial hypercholesterolemia.
Very high CV risk: history of documented coronary heart disease, ischemic stroke, peripheral artery disease, transient ischemic attack, abdominal aortic aneurysm, or carotid artery occlusion >50% without symptoms; carotid endarterectomy or carotid artery stent procedure; renal artery stenosis, or renal artery stent procedure; or type 1 or type 2 diabetes mellitus with target organ damage.
Adjusted percentages at Week 24 were obtained from a multiple imputation approach model for handling of missing data. All available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment were included.
Measured: From Baseline to Week 24
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
Adjusted percentages at Week 24 from multiple imputation approach including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection).
Measured: From Baseline to Week 24
Percentage of Participants Achieving Calculated LDL-C< 70 mg/dL (<1.81 mmol/L) at Week 24 - ITT Analysis
Adjusted percentages at Week 24 from last observation carried forward (LOCF) approach including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
Measured: From Baseline to Week 24
Percentage of Participants Achieving Calculated LDL-C <70 mg/dL (<1.81 mmol/L) at Week 24 - On-treatment Analysis
Adjusted percentages at Week 24 from LOCF approach including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection).
Measured: From Baseline to Week 24
Percent Change From Baseline in Lipoprotein (a) at Week 24 - ITT Analysis
Adjusted means and standard errors at Week 24 from a multiple imputation approach followed by robust regression model including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment.
Measured: From Baseline to Week 24
Percent Change From Baseline in Lipoprotein (a) at Week 12 - ITT Analysis
Adjusted means and standard errors at Week 12 from a multiple imputation approach followed by robust regression model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
Measured: From Baseline to Week 24
Percent Change From Baseline in HDL-C at Week 24 - ITT Analysis
Adjusted LS means and standard errors at Week 24 from MMRM including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment.
Measured: From Baseline to Week 24
Percent Change From Baseline in HDL-C at Week 12 - ITT Analysis
Adjusted LS means and standard errors at Week 12 from MMRM including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment.
Measured: From Baseline to Week 24
Percent Change From Baseline in Fasting Triglycerides at Week 24 - ITT Analysis
Adjusted means and standard errors at Week 24 from a multiple imputation approach followed by robust regression model including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment.
Measured: From Baseline to Week 24
Percent Change From Baseline in Fasting Triglycerides at Week 12 - ITT Analysis
Adjusted means and standard errors at Week 12 from a multiple imputation approach followed by robust regression model including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment.
Measured: From Baseline to Week 24
Percent Change From Baseline in Apo A-1 at Week 24 - ITT Analysis
Adjusted LS means and standard errors at Week 24 from MMRM including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment.
Measured: From Baseline to Week 24
Percent Change From Baseline in Apo A-1 at Week 12 - ITT Analysis
Adjusted LS means and standard errors at Week 12 from MMRM including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment.
Measured: From Baseline to Week 24

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

16 Dec 201330 Jun 2017

First posted30 Dec 2013 (estimated)
Study start16 Dec 2013
Primary completion27 Oct 2014
Study completion30 Jun 2017

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for HypercholesterolemiaStudies of the same condition, open and under way.
More trials run by SanofiThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Model description: A double-blind treatment period of 24 weeks (3 parallel arms) followed by an open-label extension period (single arm)
Masking: Triple blind
Who is masked: Participant, Care provider, Investigator
Enrolment: 233 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02023879
Sponsor's protocol ID: EFC13786
Other IDs: 2013-002659-14, U1111-1146-3517
Status last verified: Jun 2018
First submitted: 6 Dec 2013
Last updated: 27 Jul 2018
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

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.
PubMed 27625344

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Active, not recruitingObservational study
Study Evaluating LDL-C Change and Adherence to Inclisiran Lipid-lowering Therapy in ASCVD
Primary Hypercholesterolemia, Mixed Dyslipidemia
Active, not recruitingPhase 3
A Study of Inclisiran to Prevent Cardiovascular Events in High-risk Primary Prevention Patients.
Primary Prevention of Atherosclerotic Cardiovascular Disease
RecruitingObservational study
Causes and Natural History of Dyslipidemias
Hypercholesterolemia, Atherosclerosis
Active, not recruitingObservational study
Early Detection of Familial Hypercholesterolaemia in Pre-school Children ( CzeCH-IT)
Familial Hypercholesterolaemia
Not yet recruiting
Penn Family Screening for Familial Hypercholesterolemia (NHLBI R33) Trial 3
Familial Hypercholesterolemia

All Hypercholesterolemia trials

Study at a glance

From the registry record, last updated by the sponsor on 27 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official 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
ClinicalTrials.gov ID: NCT02023879
Acronym / sponsor ID: EFC13786
Conditions: Hypercholesterolemia
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 233 participants (actual)
Lead sponsor: SanofiIndustry (pharma, biotech, devices)
Collaborators: Regeneron Pharmaceuticals
Study start: 16 Dec 2013
Primary completion: 27 Oct 2014 (actual)
Study completion: 30 Jun 2017 (actual)
First posted: 30 Dec 2013 (estimated)
Results: Posted 15 Mar 2017

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Primary Objective:

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.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, care provider, investigator)
Number of arms: 3
Model description: A double-blind treatment period of 24 weeks (3 parallel arms) followed by an open-label extension period (single arm)

Arm	Type	Receives
Placebo Q2W	Placebo comparator	Drug: Alirocumab, Drug: Placebo (for Alirocumab), Drug: Non-statin LMT, Other: Diet AlonePeriod 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.
Alirocumab 75 mg Q2W/Up to 150 mg Q2W (Calibrator)	Other	Drug: Alirocumab, Drug: Non-statin LMT, Other: Diet AlonePeriod 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.
Alirocumab 150 mg Q4W/Up to 150 mg Q2W	Experimental	Drug: Alirocumab, Drug: Placebo (for Alirocumab), Drug: Non-statin LMT, Other: Diet AlonePeriod 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.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (1 listed)

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.

Key exclusion criteria (4 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
AlirocumabAlso: SAR236553, REGN727, Praluent®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).	Drug	Alirocumab 150 mg Q4W/Up to 150 mg Q2W, Alirocumab 75 mg Q2W/Up to 150 mg Q2W (Calibrator), Placebo Q2W
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).	Drug	Alirocumab 150 mg Q4W/Up to 150 mg Q2W, Placebo Q2W
Non-statin LMTEzetimibe or Fenofibrate at stable dose as background therapy.	Drug	Alirocumab 150 mg Q4W/Up to 150 mg Q2W, Alirocumab 75 mg Q2W/Up to 150 mg Q2W (Calibrator), Placebo Q2W
Diet AloneStable cholesterol-lowering diet as background therapy.	Other	Alirocumab 150 mg Q4W/Up to 150 mg Q2W, Alirocumab 75 mg Q2W/Up to 150 mg Q2W (Calibrator), Placebo Q2W

Primary outcome

Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent-to-Treat (ITT Analysis)
Time frame: From Baseline to Week 24
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).

25 secondary outcomes

Percent Change From Baseline in Calculated LDL-C at Week 24 - On-Treatment Analysis
Time frame: From Baseline to Week 24
Percent Change From Baseline in Calculated LDL-C at Week 12 - ITT Analysis
Time frame: From Baseline to Week 24
Percent Change From Baseline in Calculated LDL-C at Week 12 - On-Treatment Analysis
Time frame: From Baseline to Week 24
Percent Change From Baseline in Calculated LDL-C to Averaged Weeks 9 to 12 - ITT- Analysis
Time frame: From Baseline to Week 24
Percent Change From Baseline in Calculated LDL-C at Averaged Week 9 to 12 - On-Treatment Analysis
Time frame: From Baseline to Week 24
Percent Change From Baseline in Apolipoprotein (Apo) B at Week 24 - ITT Analysis
Time frame: From Baseline to Week 24
Percent Change From Baseline in Apo B at Week 24 - On-treatment Analysis
Time frame: From Baseline to Week 24
Percent Change From Baseline in Non-HDL-C at Week 24 - ITT Analysis
Time frame: From Baseline to Week 24
Percent Change From Baseline in Non-HDL-C at Week 24 - On-treatment Analysis
Time frame: From Baseline to Week 24
Percent Change From Baseline in Total-C at Week 24 - ITT Analysis
Time frame: From Baseline to Week 24
Percent Change From Baseline in Apo B at Week 12 - ITT Analysis
Time frame: From Baseline to Week 24
Percent Change From Baseline in Non-HDL-C at Week 12 - ITT Analysis
Time frame: From Baseline to Week 24
Percent Change From Baseline in Total-C at Week 12 - ITT Analysis
Time frame: From Baseline to Week 24
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
Time frame: From Baseline to Week 24
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
Time frame: From Baseline to Week 24
Percentage of Participants Achieving Calculated LDL-C< 70 mg/dL (<1.81 mmol/L) at Week 24 - ITT Analysis
Time frame: From Baseline to Week 24
Percentage of Participants Achieving Calculated LDL-C <70 mg/dL (<1.81 mmol/L) at Week 24 - On-treatment Analysis
Time frame: From Baseline to Week 24
Percent Change From Baseline in Lipoprotein (a) at Week 24 - ITT Analysis
Time frame: From Baseline to Week 24
Percent Change From Baseline in Lipoprotein (a) at Week 12 - ITT Analysis
Time frame: From Baseline to Week 24
Percent Change From Baseline in HDL-C at Week 24 - ITT Analysis
Time frame: From Baseline to Week 24
Percent Change From Baseline in HDL-C at Week 12 - ITT Analysis
Time frame: From Baseline to Week 24
Percent Change From Baseline in Fasting Triglycerides at Week 24 - ITT Analysis
Time frame: From Baseline to Week 24
Percent Change From Baseline in Fasting Triglycerides at Week 12 - ITT Analysis
Time frame: From Baseline to Week 24
Percent Change From Baseline in Apo A-1 at Week 24 - ITT Analysis
Time frame: From Baseline to Week 24
Percent Change From Baseline in Apo A-1 at Week 12 - ITT Analysis
Time frame: From Baseline to Week 24

Results and safety

Results posted to the registry on 15 Mar 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Placebo Q2W	58	54
Alirocumab 75 mg Q2W/Up to 150 mg Q2W (Calibrator)	116	107
Alirocumab 150 mg Q4W/Up to 150 mg Q2W	59	50

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

Time frame: From Baseline to Week 24. Least squares mean (Standard Error). Unit: percent change

Measure	Placebo Q2W n = 57	Alirocumab 75 mg Q2W/Up to 150 mg Q2W (Calibrator) n = 115	Alirocumab 150 mg Q4W/Up to 150 mg Q2W n = 58
Value	4.7 (2.3)	-53.5 (1.6)	-51.7 (2.3)

Placebo Q2W vs Alirocumab 150 mg Q4W/Up to 150 mg Q2W: Least square (LS) mean difference: -56.4 (95% CI -62.9 to -49.9), p <0.0001, Mixed Models Analysis

Population analysed: ITT population that included all randomized participants with one baseline and at least one post-baseline calculated LDL-C value on- or off-treatment.

25 secondary outcomes are reported in the full results.

Adverse events

Time frame: All Adverse Events (AE) were collected from signature of informed consent form up to study completion (up to 176 weeks) regardless of seriousness or relationship to investigational product.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Placebo Q2W	4 of 58 (6.9%)	28 of 58 (48.3%)	0 of 58
Alirocumab 75 mg Q2W/Up150 mg Q2W	7 of 115 (6.1%)	61 of 115 (53%)	0 of 115
Alirocumab 150 mg Q4W/Up150 mg Q2W	7 of 58 (12.1%)	29 of 58 (50%)	0 of 58
Alirocumab 150 mg Q4W (After Placebo Q2W)	15 of 51 (29.4%)	42 of 51 (82.4%)	0 of 51
Alirocumab 150 mg Q4W (After Alirocumab 75 Q2W/Up150 Q2W)	28 of 106 (26.4%)	71 of 106 (67%)	2 of 106
Alirocumab 150 mg Q4W (After Alirocumab 150 Q4W/Up150 Q2W)	14 of 48 (29.2%)	31 of 48 (64.6%)	1 of 48

Limitations and caveats (from the sponsor): 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.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 27 Jul 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 27625344Stroes 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.

Related trials for Hypercholesterolemia

Active, not recruitingObservational study
Study Evaluating LDL-C Change and Adherence to Inclisiran Lipid-lowering Therapy in ASCVD
Primary Hypercholesterolemia, Mixed Dyslipidemia
Active, not recruitingPhase 3
A Study of Inclisiran to Prevent Cardiovascular Events in High-risk Primary Prevention Patients.
Primary Prevention of Atherosclerotic Cardiovascular Disease
RecruitingObservational study
Causes and Natural History of Dyslipidemias
Hypercholesterolemia, Atherosclerosis
Active, not recruitingObservational study
Early Detection of Familial Hypercholesterolaemia in Pre-school Children ( CzeCH-IT)
Familial Hypercholesterolaemia
Not yet recruiting
Penn Family Screening for Familial Hypercholesterolemia (NHLBI R33) Trial 3
Familial Hypercholesterolemia

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Clinical Sciences & Operations study director

Sanofi

43 sites in 8 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Alirocumab, Non-statin LMT and Diet Alone in people with Hypercholesterolemia, run by Sanofi at 43 sites in 8 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 1 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 43 sites in United States, Netherlands, Spain, Canada, Denmark and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 15 Mar 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent-to-Treat (ITT Analysis) (time frame: From Baseline to Week 24). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02023879, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jul 2018.