HypercholesterolemiaPhase 3ODYSSEY FH INCT01623115
Efficacy and Safety of Alirocumab (SAR236553/REGN727) Versus Placebo on Top of Lipid-Modifying Therapy in Patients With Heterozygous Familial Hypercholesterolemia Not Adequately Controlled With Their Lipid-Modifying Therapy
A Phase 3 study testing Alirocumab and Lipid Modifying Therapy (LMT) in people with Hypercholesterolemia, run by Sanofi at 91 sites in 14 countries.
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
- 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
- 486 participants
- Where
- 91 sitesin 14 countries
- Study dates
- Jul 2012to Dec 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 heterozygous familial hypercholesterolemia who were not adequately controlled with their lipid-modifying therapy
Who cannot join
- Age < 18 years or legal age of adulthood, whichever is greater
- LDL-C < 70 mg/dL (1.81 mmol/L) and with cardiovascular disease
- LDL-C < 100 mg/dL (2.59 mmol/L) and without cardiovascular disease
- Fasting serum triglycerides > 400 mg/dL (4.52 mmol/L)
- 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
91 sites in 14 countries.
91 sites in 14 countries
United States26 sites
Investigational Site Number 840425
Auburn, Maine, 04210
Investigational Site Number 840417
Bell Gardens, California, 90201
Investigational Site Number 840411
Boston, Massachusetts, 02114
Investigational Site Number 840422
Bountiful, Utah, 84010
Investigational Site Number 840401
Charlotte, North Carolina, 28207
Investigational Site Number 840430
Cincinnati, Ohio, 45219
Investigational Site Number 840460
Dallas, Texas, 75216
Investigational Site Number 840410
Durham, North Carolina, 27710
Investigational Site Number 840455
Evanston, Illinois, 60201
Investigational Site Number 840415
Kansas City, Kansas, 66160-7321
Investigational Site Number 840429
Long Beach, California, 90801
Investigational Site Number 840419
Los Angeles, California, 90048
Investigational Site Number 840456
Miami, Florida, 33165
Investigational Site Number 840421
Mission Viejo, California, 92691
Investigational Site Number 840407
Morristown, New Jersey, 07962
Investigational Site Number 840406
Nashville, Tennessee, 37232
Investigational Site Number 840408
New York, New York, 10032
Investigational Site Number 840412
Newport Beach, California, 92660
Investigational Site Number 840428
Newport Beach, California
Investigational Site Number 840461
Northridge, California, 91324
Investigational Site Number 840404
Philadelphia, Pennsylvania, 19104
Investigational Site Number 840426
Philadelphia, Pennsylvania, 19104
Investigational Site Number 840418
Ponte Vedra, Florida, 32081
Investigational Site Number 840424
Portland, Oregon, 97201-3098
Investigational Site Number 840409
St Louis, Missouri, 63110
Investigational Site Number 840452
Washington D.C., District of Columbia, 20037
Russia10 sites
Investigational Site Number 643402
Arkhangelsk, 163000
Investigational Site Number 643407
Kazan', 420012
Investigational Site Number 643409
Moscow, 111539
Investigational Site Number 643413
Moscow, 121552
Investigational Site Number 643401
Moscow, 129301
Investigational Site Number 643412
Novisibirsk
Investigational Site Number 643408
Saint Petersburg, 193079
Investigational Site Number 643406
Saint Petersburg, 194291
Investigational Site Number 643404
Saint Petersburg, 197341
Investigational Site Number 643410
Yaroslavl, 150062
South Africa9 sites
Investigational Site Number 710401
Bloemfontein
Investigational Site Number 710405
Bloemfontein
Investigational Site Number 710406
Cap Town, 7530
Investigational Site Number 710402
Cape Town, 7708
Investigational Site Number 710407
Parktown, 2193
Investigational Site Number 710403
Parow, 7500
Investigational Site Number 710408
Pretoria
Investigational Site Number 710404
Rondebosch
Investigational Site Number 710409
Somerset West, 7130
Spain9 sites
Investigational Site Number 724403
A Coruña, 15006
Investigational Site Number 724408
Barcelona, 08036
Investigational Site Number 724406
Córdoba, 14004
Investigational Site Number 724407
L'Hospitalet de Llobregat, 08907
Investigational Site Number 724409
Madrid, 28029
Investigational Site Number 724401
Madrid, 28040
Investigational Site Number 724405
Madrid, 28040
Investigational Site Number 724404
Reus, 43201
Investigational Site Number 724402
Zaragoza, 50009
Netherlands8 sites
Investigational Site Number 528406
Amsterdam, 1105 AZ
Investigational Site Number 528410
Amsterdam
Investigational Site Number 528408
Den Helder, 1782 GZ
Investigational Site Number 528402
Groningen, 9728 NT
Investigational Site Number 528411
Leiden, 2333 ZA
Investigational Site Number 528416
Maastricht, 6229 HX
Investigational Site Number 528409
Nieuwegein, 3435 CM
Investigational Site Number 528412
Sliedrecht
Canada5 sites
Investigational Site Number 124404
Chicoutimi, G7H 5H6
Investigational Site Number 124401
Montreal, H2W 1R7
Investigational Site Number 124403
Québec, G1V 4M6
Investigational Site Number 124406
Sherbrooke, J1H 5N4
Investigational Site Number 124407
Toronto, M5C 2T2
United Kingdom5 sites
Investigational Site Number 826402
London
Investigational Site Number 826403
London
Investigational Site Number 826408
London
Investigational Site Number 826409
London
Investigational Site Number 826405
Manchester, M23 9LT
Czechia4 sites
Investigational Site Number 203401
Prague, 140 00
Investigational Site Number 203403
Prague, 180 00
Investigational Site Number 203405
Uherské Hradiště
Investigational Site Number 203402
Zlín, 760 00
Israel4 sites
Investigational Site Number 376402
Holon, 76100
Investigational Site Number 376405
Jerusalem
Investigational Site Number 376404
Safed, 13100
Investigational Site Number 376401
Tel HaShomer, 52621
Austria3 sites
Investigational Site Number 040403
Graz, 8036
Investigational Site Number 040402
Vienna, 1130
Investigational Site Number 040405
Vienna
France3 sites
Investigational Site Number 250403
Dijon, 21000
Investigational Site Number 250401
Paris, 75651
Investigational Site Number 250402
Saint-Herblain, 44093
Denmark2 sites
Investigational Site Number 208401
Copenhagen
Investigational Site Number 208403
Esbjerg, 6700
Sweden2 sites
Investigational Site Number 752404
Gothenburg, 41345
Investigational Site Number 752401
Stockholm, 111 35
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 Not Adequately Controlled 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
- Hypercholesterolemia
- Being tested
- Alirocumab, Placebo (for alirocumab), Lipid Modifying Therapy (LMT)
- Keywords
- PCSK9
- 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 group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Placebo for alirocumab every 2 weeks (Q2W) on top of stable lipid-modifying therapy (LMT) for 78 weeks. Receives: Drug: Placebo (for alirocumab); Drug: Lipid Modifying Therapy (LMT) |
| Alirocumab 75 mg/Up to 150 mg Q2W | Experimental | Alirocumab 75 mg Q2W on top of stable LMT for 78 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when low-density lipoprotein cholesterol (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 (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 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 multiple imputation approach 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 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
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 model 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 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 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jun 2012 (estimated)
- Study startJul 2012
- Primary completionApr 2014
- Study completionDec 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 (7)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
- 486 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sanofi
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Regeneron Pharmaceuticals
- Responsible party
- Sponsor
- Investigators
- Clinical Sciences & Operations, Study director, Sanofi
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01623115
- Sponsor's protocol ID
- EFC12492
- Other IDs
- U1111-1121-4275, 2011-005109-56
- Acronym
- ODYSSEY FH I
- Status last verified
- Jan 2016
- First submitted
- 15 Jun 2012
- Last updated
- 8 Feb 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 24842558Kastelein JJ, Ginsberg HN, Langslet G, Hovingh GK, Ceska R, Dufour R, Blom D, Civeira F, Krempf M, Lorenzato C, Zhao J, Pordy R, Baccara-Dinet MT, Gipe DA, Geiger MJ, Farnier M. ODYSSEY FH I and FH II: 78 week results with alirocumab treatment in 735 patients with heterozygous familial hypercholesterolaemia. Eur Heart J. 2015 Nov 14;36(43):2996-3003. doi: 10.1093/eurheartj/ehv370. Epub 2015 Sep 1.
PubMed 26330422Mahmood 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 34298554Leiter 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 30183102Defesche 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 28964736Kastelein 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 28391886Ray 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
Study at a glance
From the registry record, last updated by the sponsor on 8 Feb 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 Not Adequately Controlled With Their Lipid-Modifying Therapy
- ClinicalTrials.gov ID
- NCT01623115
- Acronym / sponsor ID
- ODYSSEY FH I / EFC12492
- Conditions
- Hypercholesterolemia
- Keywords
- PCSK9
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 486 participants (actual)
- Lead sponsor
- SanofiIndustry (pharma, biotech, devices)
- Collaborators
- Regeneron Pharmaceuticals
- Study start
- Jul 2012
- Primary completion
- Apr 2014 (actual)
- Study completion
- Dec 2014 (actual)
- First posted
- 19 Jun 2012 (estimated)
- Results
- Posted 4 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
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.
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 | Placebo comparator | Drug: Placebo (for alirocumab), Drug: Lipid Modifying Therapy (LMT)Placebo for alirocumab every 2 weeks (Q2W) on top of stable lipid-modifying therapy (LMT) for 78 weeks. |
| Alirocumab 75 mg/Up to 150 mg Q2W | Experimental | Drug: Alirocumab, Drug: Lipid Modifying Therapy (LMT)Alirocumab 75 mg Q2W on top of stable LMT for 78 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when low-density lipoprotein cholesterol (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 heterozygous familial hypercholesterolemia who were not adequately controlled with their lipid-modifying therapy
Key exclusion criteria (6 listed)
- Age < 18 years or legal age of adulthood, whichever is greater
- LDL-C < 70 mg/dL (1.81 mmol/L) and with cardiovascular disease
- LDL-C < 100 mg/dL (2.59 mmol/L) and without cardiovascular disease
- Fasting serum triglycerides > 400 mg/dL (4.52 mmol/L)
- Known history of homozygous familial hypercholesterolemia
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 75 mg/Up to 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 |
| Lipid Modifying Therapy (LMT)Statin (rosuvastatin, simvastatin or atorvastatin) at stable dose with or without other LMT as clinically indicated. | Drug | Alirocumab 75 mg/Up to 150 mg Q2W, Placebo |
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).
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
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
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Feb 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 26330422Kastelein JJ, Ginsberg HN, Langslet G, Hovingh GK, Ceska R, Dufour R, Blom D, Civeira F, Krempf M, Lorenzato C, Zhao J, Pordy R, Baccara-Dinet MT, Gipe DA, Geiger MJ, Farnier M. ODYSSEY FH I and FH II: 78 week results with alirocumab treatment in 735 patients with heterozygous familial hypercholesterolaemia. Eur Heart J. 2015 Nov 14;36(43):2996-3003. doi: 10.1093/eurheartj/ehv370. Epub 2015 Sep 1.
- 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
91 sites in 14 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 Hypercholesterolemia, run by Sanofi at 91 sites in 14 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 6 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 8 Feb 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 91 sites in United States, Russia, South Africa, Spain, Netherlands and 9 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 4 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 NCT01623115, 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 8 Feb 2016.