Study of the Safety and Efficacy of REGN727/SAR236553 in Patients With HeFH Hypercholesterolemia

NCT01266876 | Completed Phase 2 Results DMC

• 1 other identifier: R727-CL-1003
• Study Type: interventional
• Target: 77
• Locations: 2 countries
• Sites: 22

Brief Summary

The purpose of this study is to assess the efficacy and safety of REGN727/SAR236553 in participants diagnosed with heterozygous familial hypercholesterolemia (heFH)

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 investigational medicinal product (IMP) injection up to 21 days after last IMP injection (on-treatment analysis). Missing Week 12 data were imputed by last observation carried forward \[LOCF\] method.

  From Baseline to Week 12 (LOCF)

Secondary Outcomes (18)

• Absolute Change From Baseline in Calculated LDL-C at Week 12 - On-treatment Analysis

  From Baseline to Week 12 (LOCF)

• Percentage of Participants Achieving Calculated LDL-C <100 mg/dL (2.59 mmol/L) at Week 12 - On-treatment Analysis

  Week 12 (LOCF)

• Percentage of Participants Achieving LDL-C < 70 mg/dL (1.81 mmol/L) at Week 12 - On-treatment Analysis

  Week 12 (LOCF)

• Percent Change From Baseline in Total Cholesterol at Week 12 - On-treatment Analysis

  From Baseline to Week 12 (LOCF)

• Absolute Change From Baseline in Total Cholesterol at Week 12 - On-treatment Analysis

  From Baseline to Week 12 (LOCF)

Study Arms (5)

Placebo

PLACEBO COMPARATOR

Placebo SC injection Q2W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.

Drug: Placebo

Alirocumab 150 mg Q4W

EXPERIMENTAL

Alirocumab 150 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.

Drug: Alirocumab

Alirocumab 200 mg Q4W

EXPERIMENTAL

Alirocumab 200 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.

Drug: Alirocumab

Alirocumab 300 mg Q4W

EXPERIMENTAL

Alirocumab 300 mg SC injection Q4W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.

Drug: Alirocumab

Alirocumab 150 mg Q2W

EXPERIMENTAL

Alirocumab 150 mg SC injection Q2W added to stable statin regimen with or without concomitant ezetimibe for 12 weeks.

Drug: Alirocumab

Interventions

Alirocumab DRUG

Alirocumab two SC injections in the abdomen only.

Also known as: REGN727/SAR236553

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

Placebo DRUG

Placebo two SC injections in the abdomen only.

Placebo

Eligibility Criteria

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

You may qualify if:

• Must meet the World Health Organization criteria for heFH
• Participants must be on a stable statin dose, with or without ezetimibe, for at least 6 weeks before screening
• Serum LDL-C levels ≥ 100 mg/dL at screening
• Willing to follow the NCEP ATPIII TLC diet, or an equivalent diet plan, starting at screening and continuing until the last study visit
• A negative urine/serum pregnancy test at each screening visit and start of the study, for women of childbearing potential

You may not qualify if:

• Participants with homozygous FH (clinically or by previous genotyping)
• Use of a medication (other than a statin or EZE) to alter serum lipids within 42 days (6 weeks) before screening including, but not limited to:
• Fibrates
• Niacin (\>500 mg/day)
• Omega-3 fatty acids (\>1000 mg/day of DHA/EPA)
• Bile acid resins
• Use of nutraceuticals or OTC medications that may alter lipid levels that are not stable for at least 6 weeks before screening and are not planned to remain constant throughout the study. Examples include:
• Omega-3 fatty acids (≤1000 mg/day of DHA/EPA)
• Niacin (≤500 mg/day)
• Plant stanols, such as found in Benecol, flax seed oil, psyllium
• Red yeast rice
• Disorders known to influence lipid levels, such as nephrotic syndrome, significant liver disease, Cushing's disease, untreated hypothyroidism (patients on stable thyroid replacement for at least 12 weeks before the full screening visit, who are metabolically euthyroid by thyroid-stimulating hormone (TSH) testing are allowed)
• Use of thyroid medications (except for replacement therapy which has been stable for at least 12 weeks before the full screening visit)
• Fasting serum TG \>350 mg/dL screening
• LDL apheresis within 12 months before screening

Sponsors & Collaborators

• Regeneron Pharmaceuticals: lead
• Sanofi: collaborator

Study Sites (22)

Unknown Facility

Huntsville, Alabama, United States

Location

Unknown Facility

Mission Viejo, California, United States

Location

Unknown Facility

Newport Beach, California, United States

Location

Unknown Facility

Bridgeport, Connecticut, United States

Location

Unknown Facility

Jacksonville, Florida, United States

Location

Unknown Facility

Miami, Florida, United States

Location

Unknown Facility

Port Orange, Florida, United States

Location

Unknown Facility

Chicago, Illinois, United States

Location

Unknown Facility

Kansas City, Kansas, United States

Location

Unknown Facility

Auburn, Maine, United States

Location

Unknown Facility

Biddeford, Maine, United States

Location

Unknown Facility

St Louis, Missouri, United States

Location

Unknown Facility

Concord, New Hampshire, United States

Location

Unknown Facility

Durham, North Carolina, United States

Location

Unknown Facility

Cincinnati, Ohio, United States

Location

Unknown Facility

Nashville, Tennessee, United States

Location

Unknown Facility

Houston, Texas, United States

Location

Unknown Facility

Winnipeg, Manitoba, Canada

Location

Unknown Facility

London, Ontario, Canada

Location

Unknown Facility

Chicoutimi, Quebec, Canada

Location

Unknown Facility

Montreal, Quebec, Canada

Location

Unknown Facility

Saint Foy, Quebec, Canada

Location

Related Publications (4)

• 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

• Defesche JC, Stefanutti C, Langslet G, Hopkins PN, Seiz W, Baccara-Dinet MT, Hamon SC, Banerjee P, Kastelein JJP. Efficacy of alirocumab in 1191 patients with a wide spectrum of mutations in genes causative for familial hypercholesterolemia. J Clin Lipidol. 2017 Nov-Dec;11(6):1338-1346.e7. doi: 10.1016/j.jacl.2017.08.016. Epub 2017 Sep 4.

  PMID: 28964736 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

• Stein EA, Gipe D, Bergeron J, Gaudet D, Weiss R, Dufour R, Wu R, Pordy R. Effect of a monoclonal antibody to PCSK9, REGN727/SAR236553, to reduce low-density lipoprotein cholesterol in patients with heterozygous familial hypercholesterolaemia on stable statin dose with or without ezetimibe therapy: a phase 2 randomised controlled trial. Lancet. 2012 Jul 7;380(9836):29-36. doi: 10.1016/S0140-6736(12)60771-5. Epub 2012 May 26.

  PMID: 22633824 DERIVED

MeSH Terms

Conditions

Hypercholesterolemia

Interventions

alirocumab

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Clinical Trial Management
• Organization: Regeneron Pharmaceuticals, Inc

clinicaltrials@regeneron.com

Study Officials

• Clinical Trial Management

  Regeneron Pharmaceuticals

  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: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 23, 2010
• First Posted: December 24, 2010
• Study Start: January 1, 2011
• Primary Completion: November 1, 2011
• Study Completion: November 1, 2011
• Last Updated: September 22, 2015
• Results First Posted: September 22, 2015

Record last verified: 2015-08

Locations

US (17); CA (5)