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

NCT ID: NCT01288443

Last Updated: 2015-09-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 183 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-01-31
• Study Completion Date: 2011-12-31

Brief 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.

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.

Conditions

Hypercholesterolemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo Q2W

Placebo (for alirocumab) every 2 weeks (Q2W) for 12-weeks in combination with atorvastatin stable dose.

Group Type: PLACEBO_COMPARATOR

Placebo (for alirocumab)

Intervention Type: DRUG

Two subcutaneous (SC) injections in the abdomen only.

Atorvastatin

Intervention Type: DRUG

Orally once daily at a stable dose of 10 mg, 20 mg, or 40 mg as background therapy.

Alirocumab 50 mg Q2W

Alirocumab 50 mg Q2W for 12-weeks in combination with atorvastatin stable dose.

Group Type: EXPERIMENTAL

Alirocumab

Intervention Type: DRUG

Two SC injections in the abdomen only.

Atorvastatin

Intervention Type: DRUG

Orally once daily at a stable dose of 10 mg, 20 mg, or 40 mg as background therapy.

Alirocumab 100 mg Q2W

Alirocumab 100 mg Q2W for 12-weeks in combination with atorvastatin stable dose.

Group Type: EXPERIMENTAL

Alirocumab

Intervention Type: DRUG

Two SC injections in the abdomen only.

Atorvastatin

Intervention Type: DRUG

Orally once daily at a stable dose of 10 mg, 20 mg, or 40 mg as background therapy.

Alirocumab 150 mg Q2W

Alirocumab 150 mg Q2W for 12-weeks in combination with atorvastatin stable dose.

Group Type: EXPERIMENTAL

Alirocumab

Intervention Type: DRUG

Two SC injections in the abdomen only.

Atorvastatin

Intervention Type: DRUG

Orally once daily at a stable dose of 10 mg, 20 mg, or 40 mg as background therapy.

Alirocumab 200 mg Q4W

Alirocumab 200 mg every 4 weeks (Q4W) and alternating placebo Q2W for 12-weeks in combination with atorvastatin stable dose.

Group Type: EXPERIMENTAL

Alirocumab

Intervention Type: DRUG

Two SC injections in the abdomen only.

Placebo (for alirocumab)

Intervention Type: DRUG

Two subcutaneous (SC) injections in the abdomen only.

Atorvastatin

Intervention Type: DRUG

Orally once daily at a stable dose of 10 mg, 20 mg, or 40 mg as background therapy.

Alirocumab 300 mg Q4W

Alirocumab 300 mg Q4W and alternating placebo Q2W for 12-weeks in combination with atorvastatin stable dose.

Group Type: EXPERIMENTAL

Alirocumab

Intervention Type: DRUG

Two SC injections in the abdomen only.

Placebo (for alirocumab)

Intervention Type: DRUG

Two subcutaneous (SC) injections in the abdomen only.

Atorvastatin

Intervention Type: DRUG

Orally once daily at a stable dose of 10 mg, 20 mg, or 40 mg as background therapy.

Interventions

Alirocumab

Two SC injections in the abdomen only.

Intervention Type: DRUG

Placebo (for alirocumab)

Two subcutaneous (SC) injections in the abdomen only.

Intervention Type: DRUG

Atorvastatin

Orally once daily at a stable dose of 10 mg, 20 mg, or 40 mg as background therapy.

Intervention Type: DRUG

Other Intervention Names

SAR236553; REGN727

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

1. 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

2. Participants not previously instructed on a cholesterol-lowering diet

3. Participants with type 1 diabetes

4. Participants with type 2 diabetes treated with insulin

5. Participants with type 2 diabetes and with an glycated hemoglobin (HbA1c) ≥ 8.5% at screening visit (considered poorly controlled)

6. 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

7. Pregnant or breast-feeding women

8. 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Regeneron Pharmaceuticals

INDUSTRY

Sponsor Role: collaborator

Sanofi

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

Investigational Site Number 840525

Tempe, Arizona, United States

Investigational Site Number 840516

Los Angeles, California, United States

Investigational Site Number 840528

Mission Viejo, California, United States

Investigational Site Number 840509

Newport Beach, California, United States

Investigational Site Number 840523

Palm Springs, California, United States

Investigational Site Number 840534

Westlake Village, California, United States

Investigational Site Number 840530

Colorado Springs, Colorado, United States

Investigational Site Number 840504

Aventura, Florida, United States

Investigational Site Number 840519

Aventura, Florida, United States

Investigational Site Number 840514

Jacksonville, Florida, United States

Investigational Site Number 840539

Jupiter, Florida, United States

Investigational Site Number 840502

Miami, Florida, United States

Investigational Site Number 840520

Pembroke Pines, Florida, United States

Investigational Site Number 840524

Ponte Vedra, Florida, United States

Investigational Site Number 840536

Port Orange, Florida, United States

Investigational Site Number 840507

St. Petersburg, Florida, United States

Investigational Site Number 840527

Chicago, Illinois, United States

Investigational Site Number 840506

Evansville, Indiana, United States

Investigational Site Number 840529

Indianapolis, Indiana, United States

Investigational Site Number 840515

Wichita, Kansas, United States

Investigational Site Number 840532

Madisonville, Kentucky, United States

Investigational Site Number 840535

Auburn, Maine, United States

Investigational Site Number 840503

Brockton, Massachusetts, United States

Investigational Site Number 840512

Las Vegas, Nevada, United States

Investigational Site Number 840505

Edison, New Jersey, United States

Investigational Site Number 840538

Rochester, New York, United States

Investigational Site Number 840508

Raleigh, North Carolina, United States

Investigational Site Number 840522

Statesville, North Carolina, United States

Investigational Site Number 840511

Cincinnati, Ohio, United States

Investigational Site Number 840526

Cincinnati, Ohio, United States

Investigational Site Number 840510

Lyndhurst, Ohio, United States

Investigational Site Number 840533

Tulsa, Oklahoma, United States

Investigational Site Number 840537

Eugene, Oregon, United States

Investigational Site Number 840521

Bristol, Tennessee, United States

Investigational Site Number 840531

Bountiful, Utah, United States

Investigational Site Number 840517

Norfolk, Virginia, United States

Investigational Site Number 840518

Richmond, Virginia, United States

Investigational Site Number 840513

Olympia, Washington, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 22463922 (View on PubMed)

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.

Reference Type: RESULT

PMID: 25060413 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 30183102 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 26872608 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 26586732 (View on PubMed)

Other Identifiers

U1111-1116-5252

Identifier Type: OTHER

Identifier Source: secondary_id

DFI11565

Identifier Type: -

Identifier Source: org_study_id