NCT01604824

Brief Summary

The primary objective of the study is to assess the pharmacodynamic (PD) effect of alirocumab on serum low density lipoprotein cholesterol (LDL-C) during 14 weeks of subcutaneous (SC) administered alirocumab in patients with autosomal dominant hypercholesterolemia (ADH) and gain-of-function mutation (GOFm) in 1 or both alleles of the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene or with loss-of-function mutation (LOFm) in 1 or more alleles of the apolipoprotein (ApoB) gene.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
23

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started Feb 2012

Longer than P75 for phase_2

Geographic Reach
2 countries

4 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

February 22, 2012

Completed
3 months until next milestone

First Submitted

Initial submission to the registry

May 22, 2012

Completed
2 days until next milestone

First Posted

Study publicly available on registry

May 24, 2012

Completed
2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 2, 2014

Completed
3.2 years until next milestone

Study Completion

Last participant's last visit for all outcomes

July 28, 2017

Completed
2.9 years until next milestone

Results Posted

Study results publicly available

June 17, 2020

Completed
Last Updated

June 17, 2020

Status Verified

June 1, 2020

Enrollment Period

2.3 years

First QC Date

May 22, 2012

Results QC Date

August 20, 2015

Last Update Submit

June 4, 2020

Conditions

Hypercholesterolemia

Outcome Measures

Primary Outcomes (1)

  • Percent Change in Measured Serum Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 15

    By day 15, participants in groups A and C had received 1 subcutaneous (SC) dose of 150 mg alirocumab and participants in group B and D had received 1 SC dose of placebo. \[Baseline adjusted least squares (LS) means and standard errors were obtained using analysis of covariance (ANCOVA) model specifying the treatment arm as the fixed effect and the baseline measured LDL-C value as a covariate.\]

    Baseline to Day 15

Secondary Outcomes (4)

  • Percent Change in Apolipoprotein (Apo) B100 From Baseline to Day 15

    Baseline to Day 15

  • Percent Change in Non High-Density Lipoprotein Cholesterol (Non-HDL-C) From Baseline to Day 15

    Baseline to Day 15

  • Percent Change in Total Cholesterol (Total-C) From Baseline to Day 15

    Baseline to Day 15

  • Percent Change in Apolipoprotein (Apo) B100/ ApoA-1 Ratio From Baseline to Day 15

    Baseline to Day 15

Study Arms (4)

GOFm PCSK9 (Cohort 1): Alirocumab From Day 1

EXPERIMENTAL

Participants with gain-of-function mutation (GOFm) in proprotein convertase subtilisin/kexin type 9 (PCSK9) gene (Cohort 1): Alirocumab 150 mg subcutaneous (SC) injection at Week 0 (Day 1), Week 2 (Day 15), Week 4, 6 and 10 (matching placebo at Week 8, 12 and 14) during the double-blind period (Group A). Afterwards, participants have the possibility to continue in an open-label extension period with 150 mg alirocumab SC twice per week (Q2W) for an additional 3 years.

Drug: AlirocumabDrug: Placebo

GOFm PCSK9 (Cohort 1): Alirocumab From Day 15

EXPERIMENTAL

Participants with gain-of-function mutation (GOFm) in proprotein convertase subtilisin/kexin type 9 (PCSK9) gene (Cohort 1): Alirocumab 150 mg subcutaneous (SC) injection at Week 2 (Day 15), Week 4, 6, 8 and 12 (\[matching placebo at Week 0 (Day 1), 10 and 14\]) during the double-blind period (Group B). Afterwards, participants have the possibility to continue in an open-label extension period with 150 mg alirocumab SC twice per week (Q2W) for an additional 3 years.

Drug: AlirocumabDrug: Placebo

GOFm PCSK9 or LOFm ApoB (Cohort 2): Alirocumab from Day 1

EXPERIMENTAL

Participants with gain-of-function mutation (GOFm) in the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene or loss-of-function mutation (LOFm) in the apolipoprotein (Apo) B gene (Cohort 2): Alirocumab 150 mg subcutaneous (SC) injection at Week 0 (Day 1), Week 2 (Day 15), Week 4, 6 and 10 (matching placebo at Week 8, 12 and 14) during the double-blind period (Group C). Afterwards, participants have the possibility to continue in an open-label extension period with 150 mg alirocumab SC twice per week (Q2W) for an additional 3 years.

Drug: AlirocumabDrug: Placebo

GOFm PCSK9 or LOFm ApoB (Cohort 2): Alirocumab from Day 15

EXPERIMENTAL

Participants with gain-of-function mutation (GOFm) in proprotein convertase subtilisin/kexin type 9 (PCSK9) gene or loss-of-function mutation (LOFm) in apolipoprotein (Apo) B gene (Cohort 2): Alirocumab 150 mg subcutaneous (SC) injection at Week 2 (Day 15), Week 4, 6, 8 and 12 (\[matching placebo at Week 0 (Day 1), 10 and 14\]) during the double-blind period (Group D). Afterwards, participants have the possibility to continue in an open-label extension period with 150 mg alirocumab SC twice per week (Q2W) for an additional 3 years.

Drug: AlirocumabDrug: Placebo

Interventions

AlirocumabDRUG

SC injection in the abdomen

Also known as: Praluent®, REGN727, SAR236553
GOFm PCSK9 (Cohort 1): Alirocumab From Day 1GOFm PCSK9 (Cohort 1): Alirocumab From Day 15GOFm PCSK9 or LOFm ApoB (Cohort 2): Alirocumab from Day 1GOFm PCSK9 or LOFm ApoB (Cohort 2): Alirocumab from Day 15
PlaceboDRUG

SC injection in the abdomen

GOFm PCSK9 (Cohort 1): Alirocumab From Day 1GOFm PCSK9 (Cohort 1): Alirocumab From Day 15GOFm PCSK9 or LOFm ApoB (Cohort 2): Alirocumab from Day 1GOFm PCSK9 or LOFm ApoB (Cohort 2): Alirocumab from Day 15

Eligibility Criteria

Age18 Years - 70 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Between the ages of 18 and 70 years, inclusive
  • A history of molecularly confirmed PCSK9 GOFm for cohort 1 and a history of molecularly confirmed PCSK9 GOFm or ApoB LOFm
  • Plasma LDL-Cholesterol levels ≥70 mg/dL at the screening visit on a lipid-lowering therapy (LLT) regimen stable for at least 28 days

You may not qualify if:

  • Serum triglycerides \>350 mg/dL at the screening visit
  • Known to be positive for human immunodeficiency virus (HIV), hepatitis B virus, or hepatitis C virus
  • Pregnant or breast-feeding women.
  • Sexually active man or woman of childbearing potential who is unwilling to practice adequate contraception during the study

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (4)

Unknown Facility

Salt Lake City, Utah, United States

Location

Unknown Facility

Lille, Cedex, France

Location

Unknown Facility

Nantes, Cedex, France

Location

Unknown Facility

Paris, France

Location

Related Publications (2)

  • Hopkins PN, Krempf M, Bruckert E, Donahue S, Yang F, Zhang Y, DiCioccio AT. Pharmacokinetic and pharmacodynamic assessment of alirocumab in patients with familial hypercholesterolemia associated with proprotein convertase subtilisin/kexin type 9 gain-of-function or apolipoprotein B loss-of-function mutations. J Clin Lipidol. 2019 Nov-Dec;13(6):970-978. doi: 10.1016/j.jacl.2019.10.007. Epub 2019 Oct 21.

    PMID: 31767518DERIVED

  • Hopkins PN, Defesche J, Fouchier SW, Bruckert E, Luc G, Cariou B, Sjouke B, Leren TP, Harada-Shiba M, Mabuchi H, Rabes JP, Carrie A, van Heyningen C, Carreau V, Farnier M, Teoh YP, Bourbon M, Kawashiri MA, Nohara A, Soran H, Marais AD, Tada H, Abifadel M, Boileau C, Chanu B, Katsuda S, Kishimoto I, Lambert G, Makino H, Miyamoto Y, Pichelin M, Yagi K, Yamagishi M, Zair Y, Mellis S, Yancopoulos GD, Stahl N, Mendoza J, Du Y, Hamon S, Krempf M, Swergold GD. Characterization of Autosomal Dominant Hypercholesterolemia Caused by PCSK9 Gain of Function Mutations and Its Specific Treatment With Alirocumab, a PCSK9 Monoclonal Antibody. Circ Cardiovasc Genet. 2015 Dec;8(6):823-31. doi: 10.1161/CIRCGENETICS.115.001129. Epub 2015 Sep 15.

    PMID: 26374825DERIVED

Related Links

MeSH Terms

Conditions

Hypercholesterolemia

Interventions

alirocumab

Condition Hierarchy (Ancestors)

HyperlipidemiasDyslipidemiasLipid Metabolism DisordersMetabolic DiseasesNutritional and Metabolic Diseases

Results Point of Contact

Title
Clinical Trial Management
Organization
Regeneron Pharmaceuticals
clinicaltrials@regeneron.com
844-734-6643

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

May 22, 2012

First Posted

May 24, 2012

Study Start

February 22, 2012

Primary Completion

June 2, 2014

Study Completion

July 28, 2017

Last Updated

June 17, 2020

Results First Posted

June 17, 2020

Record last verified: 2020-06

Locations

US(1)FR(3)