HypercholesterolemiaPhase 3NCT01644175

Efficacy and Safety of Alirocumab (SAR236553/REGN727) Versus Placebo on Top of Lipid-Modifying Therapy in Patients With High Cardiovascular Risk and Hypercholesterolemia (ODYSSEY COMBO I)

A Phase 3 study testing Alirocumab and Lipid-Modifying Therapy (LMT) in people with Hypercholesterolemia, run by Sanofi at 76 sites in United States.

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

Alirocumab (SAR236553/REGN727) is a fully human monoclonal antibody that binds proprotein convertase subtilisin/kexin type 9 (PCSK9). Primary Objective of the study: To demonstrate the reduction of low-density lipoprotein cholesterol (LDL-C) by alirocumab as add-on therapy to stable maximally tolerated daily statin… 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 and Lipid-Modifying Therapy (LMT)
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 316 participants
Where: 76 sitesUnited States
Study dates: Jul 2012to Apr 2014
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 hypercholesterolemia and established coronary heart disease (CHD) or CHD risk equivalents who were not adequately controlled with a maximally tolerated daily dose of statin with or without other LMT, both at stable dose for at least 4 weeks to 6 weeks prior to screening (Week -2)

Who cannot join

Age <18 or legal age of adulthood, whichever was greater
Participants without established CHD or CHD risk equivalent
LDL-C <70 mg/dL (<1.81 mmol/L) and participants with a history of documented cardiovascular disease
LDL-C <100 mg/dL (<2.59 mmol/L) and participants without a history of documented cardiovascular disease
Not on a stable dose of LMT (including statin) for at least 4 weeks and/or fenofibrate for at least 6 weeks, as applicable, prior to the screening visit (Week -2) and from screening to randomization
Fasting serum triglycerides > 400 mg/dL (>4.52 mmol/L)
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

76 sites in 1 country.

City, postcode or hospital

76 sites in 1 country

United States76 sites

Investigational Site Number 840872
Anderson, South Carolina, 29621
Investigational Site Number 840890
Battle Creek, Michigan, 49015
Investigational Site Number 840857
Birmingham, Alabama, 35209
Investigational Site Number 840867
Boca Raton, Florida, 33432
Investigational Site Number 840878
Bountiful, Utah, 84010
Investigational Site Number 840884
Boynton Beach, Florida, 33472
Investigational Site Number 840870
Burbank, California, 91505
Investigational Site Number 840824
Cary, North Carolina
Investigational Site Number 840885
Charleston, South Carolina, 29407
Investigational Site Number 840842
Chicago, Illinois, 60611
Investigational Site Number 840846
Cincinnati, Ohio, 45219
Investigational Site Number 840899
Cincinnati, Ohio, 45245
Investigational Site Number 840836
Clearwater, Florida, 33761
Investigational Site Number 840850
Columbus, Georgia, 31904
Investigational Site Number 840831
Columbus, Ohio, 43231
Investigational Site Number 840866
Coral Gables, Florida, 33134
Investigational Site Number 840868
Corpus Christi, Texas, 78404
Investigational Site Number 840803
Downington, Pennsylvania, 19335
Investigational Site Number 840840
Eagle, Idaho
Investigational Site Number 840839
Edina, Minnesota, 55435
Investigational Site Number 840812
Eugene, Oregon, 97404
Investigational Site Number 840858
Eunice, Louisiana, 70535
Investigational Site Number 840898
Evanston, Illinois, 60201
Investigational Site Number 840895
Fort Lauderdale, Florida, 33308-4311
Investigational Site Number 840865
Glendale, Arizona, 85306
Investigational Site Number 840813
Greer, South Carolina, 29651
Investigational Site Number 840820
Hialeah, Florida
Investigational Site Number 840877
Houston, Texas, 77070
Investigational Site Number 840841
Houston, Texas, 77072
Investigational Site Number 840896
Indianapolis, Indiana, 46260
Investigational Site Number 840814
Jefferson City, Missouri, 65109
Investigational Site Number 840826
Jonesboro, Arkansas, 72401
Investigational Site Number 840860
Kettering, Ohio, 45429
Investigational Site Number 840851
Los Angeles, California, 90057
Investigational Site Number 840845
Los Gatos, California, 95032
Investigational Site Number 840804
Manassas, Virginia, 20110
Investigational Site Number 840805
Miami, Florida, 33143
Investigational Site Number 840894
Michigan City, Indiana, 46360
Investigational Site Number 840888
Minneapolis, Minnesota, 55455
Investigational Site Number 840838
Mishawaka, Indiana, 46545
Investigational Site Number 840891
Mobile, Alabama, 36693
Investigational Site Number 840876
Montgomery, Alabama, 36109
Investigational Site Number 840847
Morton, Illinois, 61550
Investigational Site Number 840827
Mt. Pleasant, South Carolina, 29464
Investigational Site Number 840802
New Orleans, Louisiana, 70119
Investigational Site Number 840853
New Windsor, New York, 12553
Investigational Site Number 840817
Newington, New Hampshire, 3801
Investigational Site Number 840882
Norfolk, Virginia, 23507
Investigational Site Number 840818
Norman, Oklahoma, 73069
Investigational Site Number 840819
Orem, Utah, 84058
Investigational Site Number 840811
Oviedo, Florida, 32765
Investigational Site Number 840823
Paducah, Kentucky, 42003
Investigational Site Number 840869
Philadelphia, Pennsylvania, 19146
Investigational Site Number 840825
Pittsburgh, Pennsylvania, 15206
Investigational Site Number 840837
Port Gibson, Mississippi, 39150
Investigational Site Number 840881
Port Orange, Florida, 32127
Investigational Site Number 840822
Rochester, New York, 14609
Investigational Site Number 840844
Sacramento, California, 95823
Investigational Site Number 840855
Salisbury, Massachusetts, 01952
Investigational Site Number 840863
Salt Lake City, Utah, 84102
Investigational Site Number 840830
San Antonio, Texas, 78224
Investigational Site Number 840854
San Antonio, Texas, 78229
Investigational Site Number 840883
San Antonio, Texas, 78258
Investigational Site Number 840801
San Jose, California, 95116
Investigational Site Number 840880
Smithfield, North Carolina
Investigational Site Number 840832
Southfield, Michigan, 48034
Investigational Site Number 840833
Sparks, Nevada
Investigational Site Number 840886
Tarzana, California, 91356
Investigational Site Number 840889
Tomball, Texas, 77375
Investigational Site Number 840862
Torrance, California, 90505
Investigational Site Number 840893
Vista, California, 92083
Investigational Site Number 840810
Weber City, Virginia, 24290
Investigational Site Number 840816
West Palm Beach, Florida
Investigational Site Number 840809
Willoughby Hills, Ohio, 44094
Investigational Site Number 840502
Winston-Salem, North Carolina, 27103
Investigational Site Number 840852
Winston-Salem, North Carolina, 27103

Other trials in United States

About this study

Official title: A Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study to Evaluate the Efficacy and Safety of SAR236553/REGN727 in High Cardiovascular Risk Patients With Hypercholesterolemia Not Adequately Controlled With Their Lipid-Modifying Therapy

Alirocumab (SAR236553/REGN727) is a fully human monoclonal antibody that binds proprotein convertase subtilisin/kexin type 9 (PCSK9).

Primary Objective of the study:

To demonstrate the reduction of low-density lipoprotein cholesterol (LDL-C) by alirocumab as add-on therapy to stable maximally tolerated daily statin therapy with or without other lipid-modifying therapy (LMT) in comparison with placebo after 24 weeks of treatment in high cardiovascular (CV) risk participants with hypercholesterolemia

Secondary Objectives:

To evaluate the effect of alirocumab in comparison with placebo on LDL-C at other time points
To evaluate the effect of alirocumab on other lipid parameters
To evaluate the safety and tolerability of alirocumab

Read the detailed description

The maximum study duration was 62 weeks per participant, including a 2-week screening period, 52-week randomized treatment period, and 8-week follow-up period.

Conditions: Hypercholesterolemia
Being tested: Placebo (for alirocumab), Alirocumab, Lipid-Modifying Therapy (LMT)
Medical subject headings: Hypercholesterolemia

What participants receive

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

Placebo (for 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 pre-filled pen).
AlirocumabDrug
Also called SAR236553, REGN727
Solution for injection, one subcutaneous injection in the abdomen, thigh, or outer area of upper arm with a disposable auto-injector (also known as pre-filled pen).
Lipid-Modifying Therapy (LMT)Drug
Statin (rosuvastatin, simvastatin or atorvastatin) at stable dose with or without other LMT as clinically indicated.

Study groups in NCT01644175
Study group	Role	What they receive
Placebo Q2W	Placebo comparator	Placebo (for alirocumab) every 2 weeks (Q2W) added to stable Lipid-Modifying Therapy (LMT) for 52 weeks. Receives: Drug: Placebo (for alirocumab); Drug: Lipid-Modifying Therapy (LMT)
Alirocumab	Experimental	Alirocumab 75 mg Q2W added to stable LMT for 52 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8. Receives: Drug: Alirocumab; Drug: Lipid-Modifying Therapy (LMT)

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 52 regardless of status on- or off-treatment were used in the model (ITT analysis).
Measured: From Baseline to Week 52

Secondary outcomes (22)

Percent Change From Baseline in Calculated LDL-C at Week 24 - On-Treatment Analysis
Adjusted LS means and standard errors at Week 24 were obtained from MMRM model including available post-baseline on-treatment data from Week 4 to Week 52 (i.e. up to 21 days after last injection) (on-treatment analysis).
Measured: From Baseline to Week 52
Percent Change From Baseline in Calculated LDL-C at Week 12 - ITT Analysis
Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.
Measured: From Baseline to Week 52
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 52 (i.e. up to 21 days after last injection).
Measured: From Baseline to Week 52
Percent Change From Baseline in Apolipoprotein (Apo) B at Week 24 - ITT Analysis
Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.
Measured: From baseline to Week 52
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 52 (i.e. up to 21 days after last injection).
Measured: From Baseline to Week 52
Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 24 - ITT Analysis
Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.
Measured: From Baseline to Week 52
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 52 (i.e. up to 21 days after last injection).
Measured: From Baseline to Week 52
Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24 - ITT Analysis
Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.
Measured: From Baseline to Week 52
Percent Change From Baseline in Apo B at Week 12 - ITT Analysis
Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.
Measured: From Baseline to Week 52
Percent Change From Baseline in Non-HDL-C at Week 12 - ITT Analysis
Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.
Measured: From Baseline to Week 52
Percent Change From Baseline in Total-C at Week 12 - ITT Analysis
Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.
Measured: From Baseline to Week 52
Percent Change From Baseline in Calculated LDL-C at Week 52 - ITT Analysis
Adjusted LS means and standard errors at Week 52 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.
Measured: From Baseline to Week 52
Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - ITT Analysis
Adjusted percentages at Week 24 were obtained from multiple imputation approach model for handling of missing data. All available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment were included in the imputation model.
Measured: Up to Week 52
Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - On-treatment Analysis
Adjusted percentages at Week 24 from multiple imputation approach model including available post-baseline on-treatment data from Week 4 to Week 52 i.e. up to 21 days after last injection.
Measured: Up to Week 52
Percent Change From Baseline in Lipoprotein(a) at Week 24 - ITT Analysis
Adjusted means and standard errors at Week 24 were obtained from multiple imputation approach followed by robust regression model for handling of missing data. All available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment were included in the imputation model.
Measured: From baseline to Week 52
Percent Change From Baseline in HDL-C at Week 24 - ITT Analysis
Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.
Measured: From Baseline to Week 52
Percent Change From Baseline in Fasting Triglycerides at Week 24 - ITT Analysis
Adjusted means and standard errors at Week 24 from multiple imputation approach followed be robust regression model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.
Measured: From Baseline to Week 52
Percent Change From Baseline in Apolipoprotein A-1 at Week 24 - ITT Analysis
Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.
Measured: From Baseline to Week 52
Percent Change From Baseline in Lipoprotein(a) at Week 12- ITT Analysis
Adjusted means and standard errors at Week 12 from multiple imputation approach followed by robust regression model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.
Measured: From Baseline to Week 52
Percent Change From Baseline in HDL-C at Week 12 - ITT Analysis
Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.
Measured: From Baseline to Week 52
Percent Change From Baseline in Fasting Triglycerides at Week 12 - ITT Analysis
Adjusted means and standard errors at Week 12 from multiple imputation approach followed by a robust regression model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.
Measured: From Baseline to Week 52
Percent Change From Baseline in Apo A-1 at Week 12 - ITT Analysis
Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 4 to Week 52 regardless of status on- or off-treatment.
Measured: From Baseline to Week 52

Timeline

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

Jul 2012Apr 2014

First posted18 Jul 2012 (estimated)
Study startJul 2012
Primary completionApr 2014
Study completionApr 2014

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 (5)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
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 316 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01644175
Sponsor's protocol ID: EFC11568
Other IDs: U1111-1121-4356
Status last verified: Oct 2015
First submitted: 16 Jul 2012
Last updated: 6 Nov 2015
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

Colhoun HM, Robinson JG, Farnier M, Cariou B, Blom D, Kereiakes DJ, Lorenzato C, Pordy R, Chaudhari U. Efficacy and safety of alirocumab, a fully human PCSK9 monoclonal antibody, in high cardiovascular risk patients with poorly controlled hypercholesterolemia on maximally tolerated doses of statins: rationale and design of the ODYSSEY COMBO I and II trials. BMC Cardiovasc Disord. 2014 Sep 20;14:121. doi: 10.1186/1471-2261-14-121.
PubMed 25240705
Kereiakes DJ, Robinson JG, Cannon CP, Lorenzato C, Pordy R, Chaudhari U, Colhoun HM. Efficacy and safety of the proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab among high cardiovascular risk patients on maximally tolerated statin therapy: The ODYSSEY COMBO I study. Am Heart J. 2015 Jun;169(6):906-915.e13. doi: 10.1016/j.ahj.2015.03.004. Epub 2015 Mar 13.
PubMed 26027630
Mahmood T, Minnier J, Ito MK, Li QH, Koren A, Kam IW, Fazio S, Shapiro MD. Discordant responses of plasma low-density lipoprotein cholesterol and lipoprotein(a) to alirocumab: A pooled analysis from 10 ODYSSEY Phase 3 studies. Eur J Prev Cardiol. 2021 Jul 23;28(8):816-822. doi: 10.1177/2047487320915803. Epub 2020 Apr 10.
PubMed 34298554
Leiter LA, Tinahones FJ, Karalis DG, Bujas-Bobanovic M, Letierce A, Mandel J, Samuel R, Jones PH. Alirocumab safety in people with and without diabetes mellitus: pooled data from 14 ODYSSEY trials. Diabet Med. 2018 Dec;35(12):1742-1751. doi: 10.1111/dme.13817. Epub 2018 Oct 9.
PubMed 30183102
Ray KK, Ginsberg HN, Davidson MH, Pordy R, Bessac L, Minini P, Eckel RH, Cannon CP. Reductions in Atherogenic Lipids and Major Cardiovascular Events: A Pooled Analysis of 10 ODYSSEY Trials Comparing Alirocumab With Control. Circulation. 2016 Dec 13;134(24):1931-1943. doi: 10.1161/CIRCULATIONAHA.116.024604. Epub 2016 Oct 24.
PubMed 27777279

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

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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 6 Nov 2015. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study to Evaluate the Efficacy and Safety of SAR236553/REGN727 in High Cardiovascular Risk Patients With Hypercholesterolemia Not Adequately Controlled With Their Lipid-Modifying Therapy
ClinicalTrials.gov ID: NCT01644175
Acronym / sponsor ID: EFC11568
Conditions: Hypercholesterolemia
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 316 participants (actual)
Lead sponsor: SanofiIndustry (pharma, biotech, devices)
Collaborators: Regeneron Pharmaceuticals
Study start: Jul 2012
Primary completion: Apr 2014 (actual)
Study completion: Apr 2014 (actual)
First posted: 18 Jul 2012 (estimated)
Results: Posted 6 Nov 2015

Clinical summary

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

Alirocumab (SAR236553/REGN727) is a fully human monoclonal antibody that binds proprotein convertase subtilisin/kexin type 9 (PCSK9).

Primary Objective of the study:

To demonstrate the reduction of low-density lipoprotein cholesterol (LDL-C) by alirocumab as add-on therapy to stable maximally tolerated daily statin therapy with or without other lipid-modifying therapy (LMT) in comparison with placebo after 24 weeks of treatment in high cardiovascular (CV) risk participants with hypercholesterolemia

Secondary Objectives:

To evaluate the effect of alirocumab in comparison with placebo on LDL-C at other time points
To evaluate the effect of alirocumab on other lipid parameters
To evaluate the safety and tolerability of alirocumab

Detailed description

The maximum study duration was 62 weeks per participant, including a 2-week screening period, 52-week randomized treatment period, and 8-week follow-up period.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Placebo Q2W	Placebo comparator	Drug: Placebo (for alirocumab), Drug: Lipid-Modifying Therapy (LMT)Placebo (for alirocumab) every 2 weeks (Q2W) added to stable Lipid-Modifying Therapy (LMT) for 52 weeks.
Alirocumab	Experimental	Drug: Alirocumab, Drug: Lipid-Modifying Therapy (LMT)Alirocumab 75 mg Q2W added to stable LMT for 52 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.

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 hypercholesterolemia and established coronary heart disease (CHD) or CHD risk equivalents who were not adequately controlled with a maximally tolerated daily dose of statin with or without other LMT, both at stable dose for at least 4 weeks to 6 weeks prior to screening (Week -2)

Key exclusion criteria (7 listed)

Age <18 or legal age of adulthood, whichever was greater
Participants without established CHD or CHD risk equivalent
LDL-C <70 mg/dL (<1.81 mmol/L) and participants with a history of documented cardiovascular disease
LDL-C <100 mg/dL (<2.59 mmol/L) and participants without a history of documented cardiovascular disease
Not on a stable dose of LMT (including statin) for at least 4 weeks and/or fenofibrate for at least 6 weeks, as applicable, prior to the screening visit (Week -2) and from screening to randomization

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
Placebo (for alirocumab)Solution for injection, one subcutaneous injection in the abdomen, thigh, or outer area of upper arm with a disposable auto-injector (also known as pre-filled pen).	Drug	Placebo Q2W
AlirocumabAlso: SAR236553, REGN727Solution for injection, one subcutaneous injection in the abdomen, thigh, or outer area of upper arm with a disposable auto-injector (also known as pre-filled pen).	Drug	Alirocumab
Lipid-Modifying Therapy (LMT)Statin (rosuvastatin, simvastatin or atorvastatin) at stable dose with or without other LMT as clinically indicated.	Drug	Alirocumab, 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 52
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 52 regardless of status on- or off-treatment were used in the model (ITT analysis).

22 secondary outcomes

Percent Change From Baseline in Calculated LDL-C at Week 24 - On-Treatment Analysis
Time frame: From Baseline to Week 52
Percent Change From Baseline in Calculated LDL-C at Week 12 - ITT Analysis
Time frame: From Baseline to Week 52
Percent Change From Baseline in Calculated LDL-C at Week 12 - On-Treatment Analysis
Time frame: From Baseline to Week 52
Percent Change From Baseline in Apolipoprotein (Apo) B at Week 24 - ITT Analysis
Time frame: From baseline to Week 52
Percent Change From Baseline in Apo B at Week 24 - On-treatment Analysis
Time frame: From Baseline to Week 52
Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 24 - ITT Analysis
Time frame: From Baseline to Week 52
Percent Change From Baseline in Non-HDL-C at Week 24 - On-treatment Analysis
Time frame: From Baseline to Week 52
Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24 - ITT Analysis
Time frame: From Baseline to Week 52
Percent Change From Baseline in Apo B at Week 12 - ITT Analysis
Time frame: From Baseline to Week 52
Percent Change From Baseline in Non-HDL-C at Week 12 - ITT Analysis
Time frame: From Baseline to Week 52
Percent Change From Baseline in Total-C at Week 12 - ITT Analysis
Time frame: From Baseline to Week 52
Percent Change From Baseline in Calculated LDL-C at Week 52 - ITT Analysis
Time frame: From Baseline to Week 52
Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - ITT Analysis
Time frame: Up to Week 52
Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - On-treatment Analysis
Time frame: Up to Week 52
Percent Change From Baseline in Lipoprotein(a) at Week 24 - ITT Analysis
Time frame: From baseline to Week 52
Percent Change From Baseline in HDL-C at Week 24 - ITT Analysis
Time frame: From Baseline to Week 52
Percent Change From Baseline in Fasting Triglycerides at Week 24 - ITT Analysis
Time frame: From Baseline to Week 52
Percent Change From Baseline in Apolipoprotein A-1 at Week 24 - ITT Analysis
Time frame: From Baseline to Week 52
Percent Change From Baseline in Lipoprotein(a) at Week 12- ITT Analysis
Time frame: From Baseline to Week 52
Percent Change From Baseline in HDL-C at Week 12 - ITT Analysis
Time frame: From Baseline to Week 52
Percent Change From Baseline in Fasting Triglycerides at Week 12 - ITT Analysis
Time frame: From Baseline to Week 52
Percent Change From Baseline in Apo A-1 at Week 12 - ITT Analysis
Time frame: From Baseline to Week 52

Results and safety

Results posted to the registry on 6 Nov 2015, 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	107	75
Alirocumab 75/150 mg Q2W	209	156

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

Time frame: From Baseline to Week 52. Least squares mean (Standard Error). Unit: percent change

Measure	Placebo Q2W n = 106	Alirocumab 75/150 mg Q2W n = 205
Value	-2.3 (2.7)	-48.2 (1.9)

Placebo Q2W vs Alirocumab 75/150 mg Q2W: LS Mean Difference: -45.9 (95% CI -52.5 to -39.3), p <0.0001, Mixed Models Analysis

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

22 secondary outcomes are reported in the full results.

Adverse events

Time frame: All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 60 post-treatment follow-up visit) 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	14 of 107 (13.1%)	31 of 107 (29%)	Not reported
Alirocumab 75 /up to 150 mg Q2W	26 of 207 (12.6%)	72 of 207 (34.8%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 6 Nov 2015.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 25240705Colhoun HM, Robinson JG, Farnier M, Cariou B, Blom D, Kereiakes DJ, Lorenzato C, Pordy R, Chaudhari U. Efficacy and safety of alirocumab, a fully human PCSK9 monoclonal antibody, in high cardiovascular risk patients with poorly controlled hypercholesterolemia on maximally tolerated doses of statins: rationale and design of the ODYSSEY COMBO I and II trials. BMC Cardiovasc Disord. 2014 Sep 20;14:121. doi: 10.1186/1471-2261-14-121.
Results publication: PubMed 26027630Kereiakes DJ, Robinson JG, Cannon CP, Lorenzato C, Pordy R, Chaudhari U, Colhoun HM. Efficacy and safety of the proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab among high cardiovascular risk patients on maximally tolerated statin therapy: The ODYSSEY COMBO I study. Am Heart J. 2015 Jun;169(6):906-915.e13. doi: 10.1016/j.ahj.2015.03.004. Epub 2015 Mar 13.
Derived from this study: PubMed 34298554Mahmood T, Minnier J, Ito MK, Li QH, Koren A, Kam IW, Fazio S, Shapiro MD. Discordant responses of plasma low-density lipoprotein cholesterol and lipoprotein(a) to alirocumab: A pooled analysis from 10 ODYSSEY Phase 3 studies. Eur J Prev Cardiol. 2021 Jul 23;28(8):816-822. doi: 10.1177/2047487320915803. Epub 2020 Apr 10.
Derived from this study: PubMed 30183102Leiter LA, Tinahones FJ, Karalis DG, Bujas-Bobanovic M, Letierce A, Mandel J, Samuel R, Jones PH. Alirocumab safety in people with and without diabetes mellitus: pooled data from 14 ODYSSEY trials. Diabet Med. 2018 Dec;35(12):1742-1751. doi: 10.1111/dme.13817. Epub 2018 Oct 9.
Derived from this study: PubMed 27777279Ray KK, Ginsberg HN, Davidson MH, Pordy R, Bessac L, Minini P, Eckel RH, Cannon CP. Reductions in Atherogenic Lipids and Major Cardiovascular Events: A Pooled Analysis of 10 ODYSSEY Trials Comparing Alirocumab With Control. Circulation. 2016 Dec 13;134(24):1931-1943. doi: 10.1161/CIRCULATIONAHA.116.024604. Epub 2016 Oct 24.

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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

76 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Alirocumab and Lipid-Modifying Therapy (LMT) in people with Hypercholesterolemia, run by Sanofi at 76 sites in United States.

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 7 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 6 Nov 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 76 sites in United States. 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 6 Nov 2015). 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 52). 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 NCT01644175, which also lists 5 linked publications.

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 6 Nov 2015.