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

NCT01288443 | Completed Phase 2 Results DMC

• 2 other identifiers: DFI11565U1111-1116-5252
• Study Type: interventional
• Target: 183
• Locations: 1 country
• Sites: 38

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

Conditions

Hypercholesterolemia

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline to Week 12 (LOCF)

Secondary Outcomes (6)

• Absolute Change From Baseline in Calculated LDL-C (mmol/L) at Week 12 - On-Treatment Analysis

  Baseline to Week 12 (LOCF)

• Absolute Change From Baseline in Calculated LDL-C (mg/dL) at Week 12 - On-Treatment Analysis

  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

  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

  Baseline to Week 12 (LOCF)

• Percent Change From Baseline in Fasting Triglycerides and Lipoprotein(a) at Week 12 - On-Treatment Analysis

  Baseline to Week 12 (LOCF)

Study Arms (6)

Placebo Q2W

PLACEBO COMPARATOR

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

Drug: Placebo (for alirocumab); Drug: Atorvastatin

Alirocumab 50 mg Q2W

EXPERIMENTAL

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

Drug: Alirocumab; Drug: Atorvastatin

Alirocumab 100 mg Q2W

EXPERIMENTAL

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

Drug: Alirocumab; Drug: Atorvastatin

Alirocumab 150 mg Q2W

EXPERIMENTAL

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

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.

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.

Drug: Alirocumab; Drug: Placebo (for alirocumab); Drug: Atorvastatin

Interventions

Alirocumab DRUG

Two SC injections in the abdomen only.

Also known as: SAR236553, REGN727

Alirocumab 100 mg Q2W; Alirocumab 150 mg Q2W; Alirocumab 200 mg Q4W; Alirocumab 300 mg Q4W; Alirocumab 50 mg Q2W

Placebo (for alirocumab) DRUG

Two subcutaneous (SC) injections in the abdomen only.

Alirocumab 200 mg Q4W; Alirocumab 300 mg Q4W; Placebo Q2W

Atorvastatin DRUG

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

Alirocumab 100 mg Q2W; Alirocumab 150 mg Q2W; Alirocumab 200 mg Q4W; Alirocumab 300 mg Q4W; Alirocumab 50 mg Q2W; Placebo Q2W

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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
• 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.

Sponsors & Collaborators

• Sanofi: lead
• Regeneron Pharmaceuticals: collaborator

Study Sites (38)

Investigational Site Number 840525

Tempe, Arizona, 85282, United States

Location

Investigational Site Number 840516

Los Angeles, California, 90057, United States

Location

Investigational Site Number 840528

Mission Viejo, California, 92691, United States

Location

Investigational Site Number 840509

Newport Beach, California, 92660, United States

Location

Investigational Site Number 840523

Palm Springs, California, 92262, United States

Location

Investigational Site Number 840534

Westlake Village, California, 91361, United States

Location

Investigational Site Number 840530

Colorado Springs, Colorado, 80903, United States

Location

Investigational Site Number 840504

Aventura, Florida, 33108, United States

Location

Investigational Site Number 840519

Aventura, Florida, 33108, United States

Location

Investigational Site Number 840514

Jacksonville, Florida, 32216, United States

Location

Investigational Site Number 840539

Jupiter, Florida, 33458, United States

Location

Investigational Site Number 840502

Miami, Florida, 33143, United States

Location

Investigational Site Number 840520

Pembroke Pines, Florida, 33026, United States

Location

Investigational Site Number 840524

Ponte Vedra, Florida, 32081, United States

Location

Investigational Site Number 840536

Port Orange, Florida, 32127, United States

Location

Investigational Site Number 840507

St. Petersburg, Florida, 33609, United States

Location

Investigational Site Number 840527

Chicago, Illinois, 60611, United States

Location

Investigational Site Number 840506

Evansville, Indiana, 47714, United States

Location

Investigational Site Number 840529

Indianapolis, Indiana, 46260, United States

Location

Investigational Site Number 840515

Wichita, Kansas, 67203, United States

Location

Investigational Site Number 840532

Madisonville, Kentucky, 42431, United States

Location

Investigational Site Number 840535

Auburn, Maine, 04210, United States

Location

Investigational Site Number 840503

Brockton, Massachusetts, 02301, United States

Location

Investigational Site Number 840512

Las Vegas, Nevada, 89123, United States

Location

Investigational Site Number 840505

Edison, New Jersey, 08817, United States

Location

Investigational Site Number 840538

Rochester, New York, 14609, United States

Location

Investigational Site Number 840508

Raleigh, North Carolina, 27612, United States

Location

Investigational Site Number 840522

Statesville, North Carolina, 28677, United States

Location

Investigational Site Number 840511

Cincinnati, Ohio, 45219, United States

Location

Investigational Site Number 840526

Cincinnati, Ohio, 45219, United States

Location

Investigational Site Number 840510

Lyndhurst, Ohio, 44124, United States

Location

Investigational Site Number 840533

Tulsa, Oklahoma, 74136, United States

Location

Investigational Site Number 840537

Eugene, Oregon, 97404, United States

Location

Investigational Site Number 840521

Bristol, Tennessee, 37620, United States

Location

Investigational Site Number 840531

Bountiful, Utah, 84010, United States

Location

Investigational Site Number 840517

Norfolk, Virginia, 23502, United States

Location

Investigational Site Number 840518

Richmond, Virginia, 23227, United States

Location

Investigational Site Number 840513

Olympia, Washington, 98502, United States

Location

Related Publications (5)

• 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.

  PMID: 22463922 RESULT

• 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.

  PMID: 25060413 RESULT

• 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.

  PMID: 30183102 DERIVED

• 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.

  PMID: 26872608 DERIVED

• 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.

  PMID: 26586732 DERIVED

MeSH Terms

Conditions

Hypercholesterolemia

Interventions

alirocumab; Atorvastatin

Condition Hierarchy (Ancestors)

Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi

Contact --US@sanofi.com

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 1, 2011
• First Posted: February 2, 2011
• Study Start: January 1, 2011
• Primary Completion: December 1, 2011
• Study Completion: December 1, 2011
• Last Updated: September 24, 2015
• Results First Posted: September 24, 2015

Record last verified: 2015-08

Locations

US (38)