Study of Alirocumab (REGN727/SAR236553) in Patients With Heterozygous Familial Hypercholesterolemia (HeFH) Undergoing Low-density Lipoprotein (LDL) Apheresis Therapy

NCT02326220 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: R727-CL-1216
• Study Type: interventional
• Target: 62
• Locations: 2 countries
• Sites: 13

Brief Summary

The primary objective of the study is to evaluate the effect of alirocumab 150 mg every 2 weeks (Q2W) in comparison with placebo on the frequency of low-density lipoprotein (LDL) apheresis treatments in participants with heterozygous familial hypercholesterolemia (HeFH) undergoing weekly or bi-weekly LDL apheresis therapy.

Conditions

Heterozygous Familial Hypercholesterolemia

Outcome Measures

Primary Outcomes (1)

• Change in Standardized Rate of Apheresis Treatments From Week 7 to Week 18

  Rate of apheresis treatments were normalized by the number of planned apheresis treatments according to each participant's established schedule at screening, week -10 to week -2. The normalized rate of apheresis was defined for each participant as the number of actual apheresis treatments received from week 7 to week 18 divided by the number of planned apheresis treatments per randomization strata at baseline (6 for Q2W and 12 for QW).

  Week 7 to Week 18 (before start of open-label treatment)

Secondary Outcomes (22)

• Percent Change From Baseline in Calculated LDL-C (Pre-apheresis) at Week 6

  Baseline and at Week 6

• Change in Standardized Rate of Apheresis Treatments From Week 15 to Week 18

  Week 15 up to Week 18 (before the start of open-label treatment dose)

• Percent Change From Baseline in Apolipoprotein B (Apo B) (Pre-apheresis) to Week 6

  From Baseline to Week 6

• Percent Change From Baseline in Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) (Pre-apheresis) to Week 6

  From Baseline to Week 6

• Percent Change From Baseline in Total Cholesterol (Pre-apheresis) to Week 6

  From Baseline to Week 6

Study Arms (3)

Placebo Q2W (Double Blind Period)

EXPERIMENTAL

Placebo (for alirocumab) subcutaneous (SC) injection Q2W up to Week 16.

Drug: Placebo

Alirocumab 150 mg Q2W (Double Blind Period)

EXPERIMENTAL

Alirocumab 150 mg SC injection Q2W up to Week 16.

Drug: Alirocumab

Alirocumab 150 Q2W (Open Label Treatment Period)

EXPERIMENTAL

Alirocumab 150 mg SC injection Q2W starting from Week 18 up to Week 76.

Drug: Alirocumab

Interventions

Placebo DRUG

Placebo Q2W (Double Blind Period)

Alirocumab DRUG

Also known as: REGN727, SAR236553, Praluent®

Alirocumab 150 Q2W (Open Label Treatment Period); Alirocumab 150 mg Q2W (Double Blind Period)

Eligibility Criteria

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

You may qualify if:

• Men and women ≥18 years of age at the time of the screening visit
• Diagnosis of HeFH (Heterozygous familial hypercholesterolemia)
• Currently undergoing LDL (low-density lipoprotein) apheresis therapy QW (weekly) or Q2W (every 2 weeks) or at least 8 weeks prior to the screening visit

You may not qualify if:

• Homozygous FH (familial hypercholesterolemia)
• Background medical LMT (lipid-modifying therapy) (if applicable) that has not been stable for at least 8 weeks prior to the screening visit
• LDL apheresis schedule/ apheresis settings that have not been stable for at least 8 weeks prior to the screening visit
• An LDL apheresis schedule other than QW to Q2W
• Initiation of a new exercise program or exercise that has not remained stable within 8 weeks prior to the screening visit (week -2)
• Initiation of a new diet or a diet that has not been stable within 8 weeks prior to the screening visit (week -2)
• Use of nutraceuticals or over-the-counter therapies known to affect lipids, at a dose/amount that has not been stable for at least 8 weeks prior to the screening visit (week -2), or between the screening and randomization visit
• Presence of any clinically significant uncontrolled endocrine disease known to influence serum lipids or lipoproteins
• Known history of a positive test for human immunodeficiency virus
• Use of any active investigational drugs within 1 month or 5 half-lives of screening, whichever is longer
• Patients who have been treated with at least 1 dose of alirocumab or any other anti-PCSK9 monoclonal antibody in any other clinical studies
• Pregnant or breastfeeding women

Sponsors & Collaborators

• Regeneron Pharmaceuticals: lead
• Sanofi: collaborator

Study Sites (13)

Unknown Facility

Aurora, Colorado, United States

Location

Unknown Facility

Hartford, Connecticut, United States

Location

Unknown Facility

Kansas City, Kansas, United States

Location

Unknown Facility

Scarborough, Maine, United States

Location

Unknown Facility

Rochester, Minnesota, United States

Location

Unknown Facility

Portland, Oregon, United States

Location

Unknown Facility

Philadelphia, Pennsylvania, United States

Location

Unknown Facility

Dresden, Saxony, Germany

Location

Unknown Facility

Berlin, Germany

Location

Unknown Facility

Göttingen, Germany

Location

Unknown Facility

Muenchen (2 Locations), Germany

Location

Unknown Facility

Passau, Germany

Location

Unknown Facility

Rostock, Germany

Location

Related Publications (2)

• Moriarty PM, Parhofer KG, Babirak SP, Cornier MA, Duell PB, Hohenstein B, Leebmann J, Ramlow W, Schettler V, Simha V, Steinhagen-Thiessen E, Thompson PD, Vogt A, von Stritzky B, Du Y, Manvelian G. Alirocumab in patients with heterozygous familial hypercholesterolaemia undergoing lipoprotein apheresis: the ODYSSEY ESCAPE trial. Eur Heart J. 2016 Dec 21;37(48):3588-3595. doi: 10.1093/eurheartj/ehw388. Epub 2016 Aug 29.

  PMID: 27572070 BACKGROUND

• Moriarty PM, Parhofer KG, Babirak SP, deGoma E, Duell PB, Hohenstein B, Ramlow W, Simha V, Steinhagen-Thiessen E, Thompson PD, Vogt A, von Stritzky B, Du Y, Manvelian G. Alirocumab in patients with heterozygous familial hypercholesterolemia undergoing lipoprotein apheresis: Rationale and design of the ODYSSEY ESCAPE trial. J Clin Lipidol. 2016 May-Jun;10(3):627-34. doi: 10.1016/j.jacl.2016.02.003. Epub 2016 Feb 18.

  PMID: 27206951 DERIVED

MeSH Terms

Interventions

alirocumab

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 3
• 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: December 22, 2014
• First Posted: December 29, 2014
• Study Start: March 31, 2015
• Primary Completion: January 31, 2016
• Study Completion: April 30, 2016
• Last Updated: May 1, 2020
• Results First Posted: May 1, 2020

Record last verified: 2020-04

Locations

DE (6); US (7)