HypercholesterolemiaPhase 2NCT01288443

Efficacy and Safety Evaluation of Alirocumab (SAR236553/REGN727) in Patients With Primary Hypercholesterolemia on Stable Atorvastatin Therapy

A Phase 2 study testing Alirocumab and Atorvastatin in people with Hypercholesterolemia, run by Sanofi at 38 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

Primary Objective: To evaluate the effect of alirocumab (SAR236553/REGN727) on low-density lipoprotein cholesterol (LDL-C) levels after 12 weeks of treatment in comparison with placebo in participants with LDL-C ≥ 100 mg/dL (≥ 2.59 mmol/L) on ongoing stable atorvastatin therapy. Read more about this study

Who is it for?: Ages 18 to 75 years
Conditions the study is for: Hypercholesterolemia
What is being tested?: Alirocumab and Atorvastatin
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 183 participants
Where: 38 sitesUnited States
Study dates: Jan 2011to Dec 2011
Phase: Phase 2
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 to 75 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Participants with primary hypercholesterolemia receiving a lipid-lowering treatment other than atorvastatin or not at stable dose of atorvastatin 10 mg, 20 mg, or 40 mg for at least 6 weeks prior to screening period or drug naive participants if they are likely to have low-density lipoprotein cholesterol (LDL-C) ≥ 100 mg/dL (≥ 2.59 mmol/L) at the end of the 6-week run-in treatment period on atorvastatin therapy
OR
Participants with primary hypercholesterolemia treated with atorvastatin at stable dose of 10 mg, 20 mg, or 40 mg for at least 6 weeks prior to screening period and likely to have LDL-C ≥ 100 mg/dL (≥ 2.59 mmol/L) at the screening visit

Who cannot join

LDL-C < 100 mg/dL (< 2.59 mmol/L):
After the run-in period on atorvastatin (10 mg, 20 mg, or 40 mg) for participants receiving a lipid-lowering treatment other than atorvastatin or not at stable dose of atorvastatin 10 mg, 20 mg, or 40 mg for at least 6 weeks prior to the screening, or drug naive participant
OR
At the first visit for participants who were being treated with stable dose of atorvastatin (10 mg, 20 mg, or 40 mg) for at least 6 weeks prior to screening
Participants not previously instructed on a cholesterol-lowering diet
Participants with type 1 diabetes

Show all 14Show fewer

Participants with type 2 diabetes treated with insulin
Participants with type 2 diabetes and with an glycated hemoglobin (HbA1c) ≥ 8.5% at screening visit (considered poorly controlled)
Laboratory findings measured before randomization:
Triglycerides (TG) > 350 mg/dL (> 3.95 mmol/L) at screening visit
Positive serum or urine pregnancy test in females of childbearing potential
Pregnant or breast-feeding women
Women of childbearing potential with no effective contraceptive method
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

38 sites in 1 country.

City, postcode or hospital

38 sites in 1 country

United States38 sites

Investigational Site Number 840535
Auburn, Maine, 04210
Investigational Site Number 840504
Aventura, Florida, 33108
Investigational Site Number 840519
Aventura, Florida, 33108
Investigational Site Number 840531
Bountiful, Utah, 84010
Investigational Site Number 840521
Bristol, Tennessee, 37620
Investigational Site Number 840503
Brockton, Massachusetts, 02301
Investigational Site Number 840527
Chicago, Illinois, 60611
Investigational Site Number 840511
Cincinnati, Ohio, 45219
Investigational Site Number 840526
Cincinnati, Ohio, 45219
Investigational Site Number 840530
Colorado Springs, Colorado, 80903
Investigational Site Number 840505
Edison, New Jersey, 08817
Investigational Site Number 840537
Eugene, Oregon, 97404
Investigational Site Number 840506
Evansville, Indiana, 47714
Investigational Site Number 840529
Indianapolis, Indiana, 46260
Investigational Site Number 840514
Jacksonville, Florida, 32216
Investigational Site Number 840539
Jupiter, Florida, 33458
Investigational Site Number 840512
Las Vegas, Nevada, 89123
Investigational Site Number 840516
Los Angeles, California, 90057
Investigational Site Number 840510
Lyndhurst, Ohio, 44124
Investigational Site Number 840532
Madisonville, Kentucky, 42431
Investigational Site Number 840502
Miami, Florida, 33143
Investigational Site Number 840528
Mission Viejo, California, 92691
Investigational Site Number 840509
Newport Beach, California, 92660
Investigational Site Number 840517
Norfolk, Virginia, 23502
Investigational Site Number 840513
Olympia, Washington, 98502
Investigational Site Number 840523
Palm Springs, California, 92262
Investigational Site Number 840520
Pembroke Pines, Florida, 33026
Investigational Site Number 840524
Ponte Vedra, Florida, 32081
Investigational Site Number 840536
Port Orange, Florida, 32127
Investigational Site Number 840508
Raleigh, North Carolina, 27612
Investigational Site Number 840518
Richmond, Virginia, 23227
Investigational Site Number 840538
Rochester, New York, 14609
Investigational Site Number 840507
St. Petersburg, Florida, 33609
Investigational Site Number 840522
Statesville, North Carolina, 28677
Investigational Site Number 840525
Tempe, Arizona, 85282
Investigational Site Number 840533
Tulsa, Oklahoma, 74136
Investigational Site Number 840534
Westlake Village, California, 91361
Investigational Site Number 840515
Wichita, Kansas, 67203

Other trials in United States

About this study

Official title: A Randomized, Double-blind, Parallel-group, Placebo-controlled, Multicenter Study Evaluating the Efficacy and Safety of Five Doses and Two Dose Regimens of SAR236553 Over 12 Weeks in Patients With Primary Hypercholesterolemia and LDL-cholesterol ≥ 100 mg/dL (≥ 2.59 mmol/L) on Ongoing Stable Atorvastatin Therapy

Primary Objective:

To evaluate the effect of alirocumab (SAR236553/REGN727) on low-density lipoprotein cholesterol (LDL-C) levels after 12 weeks of treatment in comparison with placebo in participants with LDL-C ≥ 100 mg/dL (≥ 2.59 mmol/L) on ongoing stable atorvastatin therapy.

Secondary Objectives:

To evaluate the effects of alirocumab on other lipid levels after 12 weeks of treatment in comparison with placebo
To evaluate the safety and tolerability of alirocumab
To evaluate the development of anti-alirocumab antibodies
To evaluate the pharmacokinetics of alirocumab

Read the detailed description

The duration of study participation depended on the status of the participant at screening:

For participants receiving atorvastatin 10 mg, 20 mg, or 40 mg at a stable dose for at least 6 weeks prior to screening, the study participation was to be approximately 21 weeks including a screening period of 1 week, a double-blind treatment period of 12 weeks and a follow-up period of 8 weeks.
For participants receiving a lipid-lowering treatment other than atorvastatin or not at stable dose of atorvastatin 10 mg, 20 mg, or 40 mg for at least 6 weeks prior to screening, or drug naive participants, the study participation was to be approximately 27 weeks including a screening period of 1 week, a run-in treatment period with atorvastatin 10 mg, 20 mg, or 40 mg at a stable dose of 6 weeks, a double-blind treatment period of 12 weeks, and a follow-up period of 8 weeks.

Conditions: Hypercholesterolemia
Being tested: Alirocumab, Placebo (for alirocumab), Atorvastatin
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
Two SC injections in the abdomen only.
Placebo (for alirocumab)Drug
Two subcutaneous (SC) injections in the abdomen only.
AtorvastatinDrug
Orally once daily at a stable dose of 10 mg, 20 mg, or 40 mg as background therapy.

Study groups in NCT01288443
Study group	Role	What they receive
Placebo Q2W	Placebo comparator	Placebo (for alirocumab) every 2 weeks (Q2W) for 12-weeks in combination with atorvastatin stable dose. Receives: Drug: Placebo (for alirocumab); Drug: Atorvastatin
Alirocumab 50 mg Q2W	Experimental	Alirocumab 50 mg Q2W for 12-weeks in combination with atorvastatin stable dose. Receives: Drug: Alirocumab; Drug: Atorvastatin
Alirocumab 100 mg Q2W	Experimental	Alirocumab 100 mg Q2W for 12-weeks in combination with atorvastatin stable dose. Receives: Drug: Alirocumab; Drug: Atorvastatin
Alirocumab 150 mg Q2W	Experimental	Alirocumab 150 mg Q2W for 12-weeks in combination with atorvastatin stable dose. Receives: Drug: Alirocumab; Drug: Atorvastatin
Alirocumab 200 mg Q4W	Experimental	Alirocumab 200 mg every 4 weeks (Q4W) and alternating placebo Q2W for 12-weeks in combination with atorvastatin stable dose. Receives: Drug: Alirocumab; Drug: Placebo (for alirocumab); Drug: Atorvastatin
Alirocumab 300 mg Q4W	Experimental	Alirocumab 300 mg Q4W and alternating placebo Q2W for 12-weeks in combination with atorvastatin stable dose. Receives: Drug: Alirocumab; Drug: Placebo (for alirocumab); Drug: Atorvastatin

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 12 - On-Treatment Analysis
Calculated LDL-C values were obtained using the Friedewald formula. Baseline adjusted least squares (LS) means and standard errors were estimated using an analysis of covariance (ANCOVA) model including available post-baseline data on treatment from first study drug injection up to 21 days after last study drug injection (on-treatment analysis). Missing Week 12 data were imputed by last observation carried forward [LOCF] method.
Measured: Baseline to Week 12 (LOCF)

Secondary outcomes (6)

Absolute Change From Baseline in Calculated LDL-C (mmol/L) at Week 12 - On-Treatment Analysis
Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.
Measured: Baseline to Week 12 (LOCF)
Absolute Change From Baseline in Calculated LDL-C (mg/dL) at Week 12 - On-Treatment Analysis
Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.
Measured: Baseline to Week 12 (LOCF)
Percentage of Participants Achieving Calculated LDL-C <100 mg/dL (2.59 mmol/L) and <70 mg/dL (1.81 mmol/L) at Week 12 - On-Treatment Analysis
Measured: Week 12 (LOCF)
Percent Change From Baseline in Total Cholesterol, High-density Lipoprotein Cholesterol (HDL-C), Non-HDL-C and Apolipoprotein B (Apo-B) at Week 12 - On-Treatment Analysis
Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.
Measured: Baseline to Week 12 (LOCF)
Percent Change From Baseline in Fasting Triglycerides and Lipoprotein(a) at Week 12 - On-Treatment Analysis
Since the assumptions of normal distribution and equality of variances were not verified for the lipid parameters, percent changes were expressed as median (inter-quartile range).
Measured: Baseline to Week 12 (LOCF)
Absolute Change in the Ratio Apolipoprotein B/Apolipoprotein A-1 (ApoB/ApoA-1) From Baseline to Week 12 - On-Treatment Analysis
Adjusted LS mean and standard errors were estimated using the same ANCOVA as for primary endpoint.
Measured: Baseline to Week 12 (LOCF)

Timeline

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

Jan 2011Dec 2011

First posted2 Feb 2011 (estimated)
Study startJan 2011
Primary completionDec 2011
Study completionDec 2011

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 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 183 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01288443
Sponsor's protocol ID: DFI11565
Other IDs: U1111-1116-5252
Status last verified: Aug 2015
First submitted: 1 Feb 2011
Last updated: 24 Sep 2015
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

McKenney JM, Koren MJ, Kereiakes DJ, Hanotin C, Ferrand AC, Stein EA. Safety and efficacy of a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 serine protease, SAR236553/REGN727, in patients with primary hypercholesterolemia receiving ongoing stable atorvastatin therapy. J Am Coll Cardiol. 2012 Jun 19;59(25):2344-53. doi: 10.1016/j.jacc.2012.03.007. Epub 2012 Mar 28.
PubMed 22463922
Gaudet D, Kereiakes DJ, McKenney JM, Roth EM, Hanotin C, Gipe D, Du Y, Ferrand AC, Ginsberg HN, Stein EA. Effect of alirocumab, a monoclonal proprotein convertase subtilisin/kexin 9 antibody, on lipoprotein(a) concentrations (a pooled analysis of 150 mg every two weeks dosing from phase 2 trials). Am J Cardiol. 2014 Sep 1;114(5):711-5. doi: 10.1016/j.amjcard.2014.05.060. Epub 2014 Jun 18.
PubMed 25060413
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
Toth PP, Hamon SC, Jones SR, Martin SS, Joshi PH, Kulkarni KR, Banerjee P, Hanotin C, Roth EM, McKenney JM. Effect of alirocumab on specific lipoprotein non-high-density lipoprotein cholesterol and subfractions as measured by the vertical auto profile method: analysis of 3 randomized trials versus placebo. Lipids Health Dis. 2016 Feb 13;15:28. doi: 10.1186/s12944-016-0197-4.
PubMed 26872608
Koren MJ, Kereiakes D, Pourfarzib R, Winegar D, Banerjee P, Hamon S, Hanotin C, McKenney JM. Effect of PCSK9 Inhibition by Alirocumab on Lipoprotein Particle Concentrations Determined by Nuclear Magnetic Resonance Spectroscopy. J Am Heart Assoc. 2015 Nov 19;4(11):e002224. doi: 10.1161/JAHA.115.002224.
PubMed 26586732

Want to know more?

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

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

Questions to ask the study team

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

See locations

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

All Hypercholesterolemia trials

Study at a glance

From the registry record, last updated by the sponsor on 24 Sep 2015. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomized, Double-blind, Parallel-group, Placebo-controlled, Multicenter Study Evaluating the Efficacy and Safety of Five Doses and Two Dose Regimens of SAR236553 Over 12 Weeks in Patients With Primary Hypercholesterolemia and LDL-cholesterol ≥ 100 mg/dL (≥ 2.59 mmol/L) on Ongoing Stable Atorvastatin Therapy
ClinicalTrials.gov ID: NCT01288443
Acronym / sponsor ID: DFI11565
Conditions: Hypercholesterolemia
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 183 participants (actual)
Lead sponsor: SanofiIndustry (pharma, biotech, devices)
Collaborators: Regeneron Pharmaceuticals
Study start: Jan 2011
Primary completion: Dec 2011 (actual)
Study completion: Dec 2011 (actual)
First posted: 2 Feb 2011 (estimated)
Results: Posted 24 Sep 2015

Clinical summary

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

Primary Objective:

To evaluate the effect of alirocumab (SAR236553/REGN727) on low-density lipoprotein cholesterol (LDL-C) levels after 12 weeks of treatment in comparison with placebo in participants with LDL-C ≥ 100 mg/dL (≥ 2.59 mmol/L) on ongoing stable atorvastatin therapy.

Secondary Objectives:

To evaluate the effects of alirocumab on other lipid levels after 12 weeks of treatment in comparison with placebo
To evaluate the safety and tolerability of alirocumab
To evaluate the development of anti-alirocumab antibodies
To evaluate the pharmacokinetics of alirocumab

Detailed description

The duration of study participation depended on the status of the participant at screening:

For participants receiving atorvastatin 10 mg, 20 mg, or 40 mg at a stable dose for at least 6 weeks prior to screening, the study participation was to be approximately 21 weeks including a screening period of 1 week, a double-blind treatment period of 12 weeks and a follow-up period of 8 weeks.
For participants receiving a lipid-lowering treatment other than atorvastatin or not at stable dose of atorvastatin 10 mg, 20 mg, or 40 mg for at least 6 weeks prior to screening, or drug naive participants, the study participation was to be approximately 27 weeks including a screening period of 1 week, a run-in treatment period with atorvastatin 10 mg, 20 mg, or 40 mg at a stable dose of 6 weeks, a double-blind treatment period of 12 weeks, and a follow-up period of 8 weeks.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 6

Arm	Type	Receives
Placebo Q2W	Placebo comparator	Drug: Placebo (for alirocumab), Drug: AtorvastatinPlacebo (for alirocumab) every 2 weeks (Q2W) for 12-weeks in combination with atorvastatin stable dose.
Alirocumab 50 mg Q2W	Experimental	Drug: Alirocumab, Drug: AtorvastatinAlirocumab 50 mg Q2W for 12-weeks in combination with atorvastatin stable dose.
Alirocumab 100 mg Q2W	Experimental	Drug: Alirocumab, Drug: AtorvastatinAlirocumab 100 mg Q2W for 12-weeks in combination with atorvastatin stable dose.
Alirocumab 150 mg Q2W	Experimental	Drug: Alirocumab, Drug: AtorvastatinAlirocumab 150 mg Q2W for 12-weeks in combination with atorvastatin stable dose.
Alirocumab 200 mg Q4W	Experimental	Drug: Alirocumab, Drug: Placebo (for alirocumab), Drug: AtorvastatinAlirocumab 200 mg every 4 weeks (Q4W) and alternating placebo Q2W for 12-weeks in combination with atorvastatin stable dose.
Alirocumab 300 mg Q4W	Experimental	Drug: Alirocumab, Drug: Placebo (for alirocumab), Drug: AtorvastatinAlirocumab 300 mg Q4W and alternating placebo Q2W for 12-weeks in combination with atorvastatin stable dose.

Who may qualify

Ages: 18 to 75 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

Participants with primary hypercholesterolemia receiving a lipid-lowering treatment other than atorvastatin or not at stable dose of atorvastatin 10 mg, 20 mg, or 40 mg for at least 6 weeks prior to screening period or drug naive participants if they are likely to have low-density lipoprotein cholesterol (LDL-C) ≥ 100 mg/dL (≥ 2.59 mmol/L) at the end of the 6-week run-in treatment period on atorvastatin therapy
OR
Participants with primary hypercholesterolemia treated with atorvastatin at stable dose of 10 mg, 20 mg, or 40 mg for at least 6 weeks prior to screening period and likely to have LDL-C ≥ 100 mg/dL (≥ 2.59 mmol/L) at the screening visit

Key exclusion criteria (14 listed)

LDL-C < 100 mg/dL (< 2.59 mmol/L):
OR
Participants not previously instructed on a cholesterol-lowering diet
Participants with type 1 diabetes
Participants with type 2 diabetes treated with insulin

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, REGN727Two SC injections in the abdomen only.	Drug	Alirocumab 100 mg Q2W, Alirocumab 150 mg Q2W, Alirocumab 200 mg Q4W, Alirocumab 300 mg Q4W, Alirocumab 50 mg Q2W
Placebo (for alirocumab)Two subcutaneous (SC) injections in the abdomen only.	Drug	Alirocumab 200 mg Q4W, Alirocumab 300 mg Q4W, Placebo Q2W
AtorvastatinOrally once daily at a stable dose of 10 mg, 20 mg, or 40 mg as background therapy.	Drug	Alirocumab 100 mg Q2W, Alirocumab 150 mg Q2W, Alirocumab 200 mg Q4W, Alirocumab 300 mg Q4W, Alirocumab 50 mg Q2W, Placebo Q2W

Primary outcome

Percent Change From Baseline in Calculated LDL-C at Week 12 - On-Treatment Analysis
Time frame: Baseline to Week 12 (LOCF)
Calculated LDL-C values were obtained using the Friedewald formula. Baseline adjusted least squares (LS) means and standard errors were estimated using an analysis of covariance (ANCOVA) model including available post-baseline data on treatment from first study drug injection up to 21 days after last study drug injection (on-treatment analysis). Missing Week 12 data were imputed by last observation carried forward [LOCF] method.

6 secondary outcomes

Absolute Change From Baseline in Calculated LDL-C (mmol/L) at Week 12 - On-Treatment Analysis
Time frame: Baseline to Week 12 (LOCF)
Absolute Change From Baseline in Calculated LDL-C (mg/dL) at Week 12 - On-Treatment Analysis
Time frame: Baseline to Week 12 (LOCF)
Percentage of Participants Achieving Calculated LDL-C <100 mg/dL (2.59 mmol/L) and <70 mg/dL (1.81 mmol/L) at Week 12 - On-Treatment Analysis
Time frame: Week 12 (LOCF)
Percent Change From Baseline in Total Cholesterol, High-density Lipoprotein Cholesterol (HDL-C), Non-HDL-C and Apolipoprotein B (Apo-B) at Week 12 - On-Treatment Analysis
Time frame: Baseline to Week 12 (LOCF)
Percent Change From Baseline in Fasting Triglycerides and Lipoprotein(a) at Week 12 - On-Treatment Analysis
Time frame: Baseline to Week 12 (LOCF)
Absolute Change in the Ratio Apolipoprotein B/Apolipoprotein A-1 (ApoB/ApoA-1) From Baseline to Week 12 - On-Treatment Analysis
Time frame: Baseline to Week 12 (LOCF)

Results and safety

Results posted to the registry on 24 Sep 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	31	31
Alirocumab 50 mg Q2W	30	29
Alirocumab 100 mg Q2W	31	30
Alirocumab 150 mg Q2W	31	27
Alirocumab 200 mg Q4W	30	23
Alirocumab 300 mg Q4W	30	25

Primary outcome: Percent Change From Baseline in Calculated LDL-C at Week 12 - On-Treatment Analysis

Time frame: Baseline to Week 12 (LOCF). Least squares mean (Standard Error). Unit: percent change

Measure	Placebo n = 31	Alirocumab 50 mg Q2W n = 30	Alirocumab 100 mg Q2W n = 31	Alirocumab 150 mg Q2W n = 29	Alirocumab 200 mg Q4W n = 28	Alirocumab 300 mg Q4W n = 30
Value	-5.1 (3.1)	-39.6 (3.2)	-64.2 (3.1)	-72.4 (3.2)	-43.2 (3.3)	-47.7 (3.2)

Placebo vs Alirocumab 150 mg Q2W: p <0.0001, ANCOVA
Placebo vs Alirocumab 300 mg Q4W: p <0.0001, ANCOVA
Placebo vs Alirocumab 100 mg Q2W: p <0.0001, ANCOVA

Population analysed: Modified Intent-To-Treat (mITT) population included all randomized participants with one baseline and at least one post baseline on-treatment calculated LDL-C.

6 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 20) regardless of seriousness or relationship to investigational medicinal product (IMP).. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Placebo	1 of 31 (3.2%)	10 of 31 (32.3%)	Not reported
Alirocumab 50 mg Q2W	0 of 30 (0%)	14 of 30 (46.7%)	Not reported
Alirocumab 100 mg Q2W	1 of 31 (3.2%)	14 of 31 (45.2%)	Not reported
Alirocumab 150 mg Q2W	0 of 31 (0%)	12 of 31 (38.7%)	Not reported
Alirocumab 200 mg Q4W	1 of 31 (3.2%)	12 of 31 (38.7%)	Not reported
Alirocumab 300 mg Q4W	1 of 28 (3.6%)	10 of 28 (35.7%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 24 Sep 2015.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 22463922McKenney JM, Koren MJ, Kereiakes DJ, Hanotin C, Ferrand AC, Stein EA. Safety and efficacy of a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 serine protease, SAR236553/REGN727, in patients with primary hypercholesterolemia receiving ongoing stable atorvastatin therapy. J Am Coll Cardiol. 2012 Jun 19;59(25):2344-53. doi: 10.1016/j.jacc.2012.03.007. Epub 2012 Mar 28.
Results publication: PubMed 25060413Gaudet D, Kereiakes DJ, McKenney JM, Roth EM, Hanotin C, Gipe D, Du Y, Ferrand AC, Ginsberg HN, Stein EA. Effect of alirocumab, a monoclonal proprotein convertase subtilisin/kexin 9 antibody, on lipoprotein(a) concentrations (a pooled analysis of 150 mg every two weeks dosing from phase 2 trials). Am J Cardiol. 2014 Sep 1;114(5):711-5. doi: 10.1016/j.amjcard.2014.05.060. Epub 2014 Jun 18.
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 26872608Toth PP, Hamon SC, Jones SR, Martin SS, Joshi PH, Kulkarni KR, Banerjee P, Hanotin C, Roth EM, McKenney JM. Effect of alirocumab on specific lipoprotein non-high-density lipoprotein cholesterol and subfractions as measured by the vertical auto profile method: analysis of 3 randomized trials versus placebo. Lipids Health Dis. 2016 Feb 13;15:28. doi: 10.1186/s12944-016-0197-4.
Derived from this study: PubMed 26586732Koren MJ, Kereiakes D, Pourfarzib R, Winegar D, Banerjee P, Hamon S, Hanotin C, McKenney JM. Effect of PCSK9 Inhibition by Alirocumab on Lipoprotein Particle Concentrations Determined by Nuclear Magnetic Resonance Spectroscopy. J Am Heart Assoc. 2015 Nov 19;4(11):e002224. doi: 10.1161/JAHA.115.002224.

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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

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

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Alirocumab and Atorvastatin in people with Hypercholesterolemia, run by Sanofi at 38 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 3 inclusion and 14 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 24 Sep 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 38 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 24 Sep 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 12 - On-Treatment Analysis (time frame: Baseline to Week 12 (LOCF)). 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 NCT01288443, 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 24 Sep 2015.