HypercholesterolaemiaPhase 3NCT01617655

Efficacy and Safety of Alirocumab (SAR236553/REGN727) Versus Placebo on Top of Lipid-Modifying Therapy in Patients With Heterozygous Familial Hypercholesterolemia (ODYSSEY HIGH FH)

A Phase 3 study testing Alirocumab and Lipid Modifying Therapy (LMT) in people with Hypercholesterolaemia, run by Sanofi at 35 sites in 5 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

Alirocumab (SAR236553/REGN727) is a fully human monoclonal antibody that binds PCSK9 (proprotein convertase subtilisin/kexin type 9). Primary Objective of the study: To evaluate the effect of alirocumab on low-density lipoprotein cholesterol (LDL-C) levels after 24 weeks of treatment in comparison with placebo. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Hypercholesterolaemia
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: 107 participants
Where: 35 sitesin 5 countries
Study dates: Jun 2012to Jan 2015
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 heterozygous familial hypercholesterolemia who were not adequately controlled with their lipid-modifying therapy.

Who cannot join

Age < 18 years
LDL-C < 160 mg/dL (< 4.14 mmol/L) at the screening visit (Week-3).
Fasting serum triglycerides > 400 mg/dL (> 4.52 mmol/L) during the screening period.
Known history of homozygous familial hypercholesterolemia.
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

35 sites in 5 countries.

Country

City, postcode or hospital

35 sites in 5 countries

United States14 sites

Investigational Site Number 840742
Bell Gardens, California, 90201
Investigational Site Number 840714
Cincinnati, Ohio, 45219
Investigational Site Number 840736
Dallas, Texas, 75216
Investigational Site Number 840702
Durham, North Carolina, 27710
Investigational Site Number 840738
Miami, Florida, 33165
Investigational Site Number 840701
New York, New York, 10032
Investigational Site Number 840703
Newport Beach, California, 92660
Investigational Site Number 840712
Newport Beach, California, 92663
Investigational Site Number 840743
Northridge, California, 91324
Investigational Site Number 840705
Philadelphia, Pennsylvania, 19104
Investigational Site Number 840709
Philadelphia, Pennsylvania, 19104
Investigational Site Number 840713
Philadelphia, Pennsylvania, 19104
Investigational Site Number 840710
Ponte Vedra, Florida, 32081
Investigational Site Number 840734
Washington D.C., District of Columbia, 20037

Other trials in United States

Russia9 sites

Investigational Site Number 643706
Arkhangelsk, 163000
Investigational Site Number 643705
Kazan', 420012
Investigational Site Number 643703
Moscow, 111539
Investigational Site Number 643711
Moscow, 121552
Investigational Site Number 643708
Moscow, 129301
Investigational Site Number 643710
Saint Petersburg, 193079
Investigational Site Number 643709
Saint Petersburg, 194291
Investigational Site Number 643702
Saint Petersburg, 197341
Investigational Site Number 643707
Yaroslavl, 150062

Other trials in Russia

Netherlands5 sites

Investigational Site Number 528713
Amsterdam, 1091 AC
Investigational Site Number 528701
Amsterdam, 1105 AZ
Investigational Site Number 528704
Groningen, 9728 NT
Investigational Site Number 528716
Leiden, 2333 ZA
Investigational Site Number 528709
Utrecht, 3582 KE

Other trials in Netherlands

South Africa5 sites

Investigational Site Number 710701
Bloemfontein, 9301
Investigational Site Number 710704
Bloemfontein, 9301
Investigational Site Number 710706
Cap Town, 7530
Investigational Site Number 710702
Parktown, 2193
Investigational Site Number 710703
Somerset West, 7130

Other trials in South Africa

Canada2 sites

Investigational Site Number 124704
Québec, G1V 4M6
Investigational Site Number 124703
Sherbrooke, J1H 5N4

Other trials in Canada

About this study

Official title: A Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study to Evaluate the Efficacy and Safety of SAR236553/REGN727 in Patients With Heterozygous Familial Hypercholesterolemia and LDL-C Higher or Equal to 160mg/dL With Their Lipid-Modifying Therapy

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

Primary Objective of the study:

To evaluate the effect of alirocumab on low-density lipoprotein cholesterol (LDL-C) levels after 24 weeks of treatment in comparison with placebo.

Secondary Objectives:

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

Read the detailed description

The maximum study duration was planned to be 89 weeks per participant including participants who successfully completed the 78-week treatment period had the possibility to join an open-label extension study (LTS13463, NCT01954394) at the end of the treatment period.

Conditions: Hypercholesterolaemia
Being tested: Alirocumab, Placebo (for 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.

AlirocumabDrug
Also called SAR236553, REGN727, Praluent
Solution for subcutaneous 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 subcutaneous 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).
Lipid Modifying Therapy (LMT)Drug
Statin (rosuvastatin, simvastatin or atorvastatin) at stable dose with or without other LMT as clinically indicated.

Study groups in NCT01617655
Study group	Role	What they receive
Placebo Q2W	Placebo comparator	Placebo for alirocumab subcutaneous (SC) injection every two weeks (Q2W) on top of stable lipid-modifying therapy (LMT) for 78 weeks. Receives: Drug: Placebo (for alirocumab); Drug: Lipid Modifying Therapy (LMT)
Alirocumab 150 mg Q2W	Experimental	Alirocumab 150 mg SC injection Q2W on top of stable LMT for 78 weeks. 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 - 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 (24)

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 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 B (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 Very High Cardiovascular (CV) Risk Participants Achieving Calculated LDL-C < 70 mg/dL (<1.81 mmol/L) or High CV Risk Participants Achieving Calculated LDL-C < 100 mg/dL (<2.59 mmol/L) at Week 24 - ITT Analysis
Very high CV risk participants: Heterozygous Familial Hypercholesterolemia (heFH) participants with coronary heart disease (CHD) or CHD risk equivalents. High CV risk participants: heFH participants without CHD or CHD risk equivalents. CHD risk equivalent: peripheral arterial disease, ischemic stroke, moderate chronic kidney disease (estimated glomerular filtration rate, 30 to <60 ml/minute/1.73 m^2 of body-surface area), or diabetes mellitus plus 2 or more additional risk factors (hypertension; ankle-brachial index of ≤0.90; microalbuminuria, macroalbuminuria, or a urinary dipstick result of >2+ protein; preproliferative or proliferative retinopathy or laser treatment for retinopathy; or a family history of premature CHD). 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 52 regardless of status on- or off-treatment were included in the imputation model.
Measured: Up to Week 52
Percentage of Very High CV Risk Participants Achieving Calculated LDL-C < 70 mg/dL (<1.81 mmol/L) 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 a 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 from a 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 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 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 Apolipoprotein A-1 (Apo 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 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
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 multiple imputation approach including all available post-baseline data from Week 4 to Week 52 regardless of status on-or off-treatment.
Measured: Up to Week 52
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 multiple imputation approach 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

Timeline

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

Jun 2012Jan 2015

First posted12 Jun 2012 (estimated)
Study startJun 2012
Primary completionMay 2014
Study completionJan 2015

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 (7)Papers the sponsor has linked to this study.
Other trials for HypercholesterolaemiaStudies 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: 107 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01617655
Sponsor's protocol ID: EFC12732
Other IDs: U1111-1128-5459, 2012-001096-37
Status last verified: Sep 2016
First submitted: 8 Jun 2012
Last updated: 4 Oct 2016
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

Kastelein JJ, Robinson JG, Farnier M, Krempf M, Langslet G, Lorenzato C, Gipe DA, Baccara-Dinet MT. Efficacy and safety of alirocumab in patients with heterozygous familial hypercholesterolemia not adequately controlled with current lipid-lowering therapy: design and rationale of the ODYSSEY FH studies. Cardiovasc Drugs Ther. 2014 Jun;28(3):281-9. doi: 10.1007/s10557-014-6523-z.
PubMed 24842558
Ginsberg HN, Rader DJ, Raal FJ, Guyton JR, Baccara-Dinet MT, Lorenzato C, Pordy R, Stroes E. Efficacy and Safety of Alirocumab in Patients with Heterozygous Familial Hypercholesterolemia and LDL-C of 160 mg/dl or Higher. Cardiovasc Drugs Ther. 2016 Oct;30(5):473-483. doi: 10.1007/s10557-016-6685-y.
PubMed 27618825
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
Defesche JC, Stefanutti C, Langslet G, Hopkins PN, Seiz W, Baccara-Dinet MT, Hamon SC, Banerjee P, Kastelein JJP. Efficacy of alirocumab in 1191 patients with a wide spectrum of mutations in genes causative for familial hypercholesterolemia. J Clin Lipidol. 2017 Nov-Dec;11(6):1338-1346.e7. doi: 10.1016/j.jacl.2017.08.016. Epub 2017 Sep 4.
PubMed 28964736
Kastelein JJ, Hovingh GK, Langslet G, Baccara-Dinet MT, Gipe DA, Chaudhari U, Zhao J, Minini P, Farnier M. Efficacy and safety of the proprotein convertase subtilisin/kexin type 9 monoclonal antibody alirocumab vs placebo in patients with heterozygous familial hypercholesterolemia. J Clin Lipidol. 2017 Jan-Feb;11(1):195-203.e4. doi: 10.1016/j.jacl.2016.12.004. Epub 2016 Dec 28.
PubMed 28391886
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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Study Evaluating LDL-C Change and Adherence to Inclisiran Lipid-lowering Therapy in ASCVD
Primary Hypercholesterolemia, Mixed Dyslipidemia
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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 Hypercholesterolaemia trials

Study at a glance

From the registry record, last updated by the sponsor on 4 Oct 2016. 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 Patients With Heterozygous Familial Hypercholesterolemia and LDL-C Higher or Equal to 160mg/dL With Their Lipid-Modifying Therapy
ClinicalTrials.gov ID: NCT01617655
Acronym / sponsor ID: EFC12732
Conditions: Hypercholesterolaemia
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 107 participants (actual)
Lead sponsor: SanofiIndustry (pharma, biotech, devices)
Collaborators: Regeneron Pharmaceuticals
Study start: Jun 2012
Primary completion: May 2014 (actual)
Study completion: Jan 2015 (actual)
First posted: 12 Jun 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 PCSK9 (proprotein convertase subtilisin/kexin type 9).

Primary Objective of the study:

To evaluate the effect of alirocumab on low-density lipoprotein cholesterol (LDL-C) levels after 24 weeks of treatment in comparison with placebo.

Secondary Objectives:

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

Detailed description

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 subcutaneous (SC) injection every two weeks (Q2W) on top of stable lipid-modifying therapy (LMT) for 78 weeks.
Alirocumab 150 mg Q2W	Experimental	Drug: Alirocumab, Drug: Lipid Modifying Therapy (LMT)Alirocumab 150 mg SC injection Q2W on top of stable LMT for 78 weeks.

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 heterozygous familial hypercholesterolemia who were not adequately controlled with their lipid-modifying therapy.

Key exclusion criteria (5 listed)

Age < 18 years
LDL-C < 160 mg/dL (< 4.14 mmol/L) at the screening visit (Week-3).
Fasting serum triglycerides > 400 mg/dL (> 4.52 mmol/L) during the screening period.
Known history of homozygous familial hypercholesterolemia.
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, PraluentSolution for subcutaneous 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 Q2W
Placebo (for alirocumab)Solution for subcutaneous 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	Placebo Q2W
Lipid Modifying Therapy (LMT)Statin (rosuvastatin, simvastatin or atorvastatin) at stable dose with or without other LMT as clinically indicated.	Drug	Alirocumab 150 mg Q2W, Placebo Q2W

Primary outcome

Percent Change From Baseline in Calculated LDL-C at Week 24 - 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).

24 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 B (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 Very High Cardiovascular (CV) Risk Participants Achieving Calculated LDL-C < 70 mg/dL (<1.81 mmol/L) or High CV Risk Participants Achieving Calculated LDL-C < 100 mg/dL (<2.59 mmol/L) at Week 24 - ITT Analysis
Time frame: Up to Week 52
Percentage of Very High CV Risk Participants Achieving Calculated LDL-C < 70 mg/dL (<1.81 mmol/L) or High CV Risk Participants Achieving Calculated LDL-C < 100 mg/dL (<2.59 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 (Apo 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
Percentage of Participants Achieving Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - ITT Analysis
Time frame: Up to Week 52
Percentage of Participants Achieving Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - On-Treatment Analysis
Time frame: Up 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	35	26
Alirocumab 150 mg Q2W	72	43

Primary outcome: Percent Change From Baseline in Calculated LDL-C at Week 24 - ITT Analysis

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

Measure	Placebo Q2W n = 35	Alirocumab 150 mg Q2W n = 71
Value	-6.6 (4.9)	-45.7 (3.5)

Placebo Q2W vs Alirocumab 150 mg Q2W: LS mean difference: -39.1 (95% CI -51.1 to -27.1), 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.

24 secondary outcomes are reported in the full results.

Adverse events

Time frame: All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit in the study regardless of seriousness or relationship to study drug.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Placebo Q2W	4 of 35 (11.4%)	20 of 35 (57.1%)	Not reported
Alirocumab 150 Q2W	10 of 72 (13.9%)	39 of 72 (54.2%)	Not reported

Limitations and caveats (from the sponsor): Manual reclassification was done by the Sponsor for the "other reasons" of non-completion of study as specified in the electronic case report form (eCRF).

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 4 Oct 2016.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 24842558Kastelein JJ, Robinson JG, Farnier M, Krempf M, Langslet G, Lorenzato C, Gipe DA, Baccara-Dinet MT. Efficacy and safety of alirocumab in patients with heterozygous familial hypercholesterolemia not adequately controlled with current lipid-lowering therapy: design and rationale of the ODYSSEY FH studies. Cardiovasc Drugs Ther. 2014 Jun;28(3):281-9. doi: 10.1007/s10557-014-6523-z.
Results publication: PubMed 27618825Ginsberg HN, Rader DJ, Raal FJ, Guyton JR, Baccara-Dinet MT, Lorenzato C, Pordy R, Stroes E. Efficacy and Safety of Alirocumab in Patients with Heterozygous Familial Hypercholesterolemia and LDL-C of 160 mg/dl or Higher. Cardiovasc Drugs Ther. 2016 Oct;30(5):473-483. doi: 10.1007/s10557-016-6685-y.
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 28964736Defesche JC, Stefanutti C, Langslet G, Hopkins PN, Seiz W, Baccara-Dinet MT, Hamon SC, Banerjee P, Kastelein JJP. Efficacy of alirocumab in 1191 patients with a wide spectrum of mutations in genes causative for familial hypercholesterolemia. J Clin Lipidol. 2017 Nov-Dec;11(6):1338-1346.e7. doi: 10.1016/j.jacl.2017.08.016. Epub 2017 Sep 4.
Derived from this study: PubMed 28391886Kastelein JJ, Hovingh GK, Langslet G, Baccara-Dinet MT, Gipe DA, Chaudhari U, Zhao J, Minini P, Farnier M. Efficacy and safety of the proprotein convertase subtilisin/kexin type 9 monoclonal antibody alirocumab vs placebo in patients with heterozygous familial hypercholesterolemia. J Clin Lipidol. 2017 Jan-Feb;11(1):195-203.e4. doi: 10.1016/j.jacl.2016.12.004. Epub 2016 Dec 28.
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

35 sites in 5 countries: 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 Hypercholesterolaemia, run by Sanofi at 35 sites in 5 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 5 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 4 Oct 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 35 sites in United States, Russia, Netherlands, South Africa, Canada. 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 - 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 NCT01617655, which also lists 7 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 4 Oct 2016.