Clinical trial NCT01604824: A Study of Alirocumab in Participants With Autosomal Dominant Hypercholesterolemia (ADH) and Gain-of-Function Mutations (GOFm) of the Proprotein Convertase Subtilisin Kexin 9 (PCSK9) Gene or Loss-of-Function Mutations (LOFm) of the Apolipoprotein (Apo) B Gene
Official title: A Phase 2 Pilot Study With a Randomized Double-Blind Treatment Phase to Evaluate the Pharmacodynamics and Safety of Alirocumab in Patients With Autosomal Dominant Hypercholesterolemia and Gain-of-Function Mutations in 1 or Both Alleles of the PCSK9 Gene or Loss-of-Function Mutations in 1 or More Alleles of the Loss-of-Function Mutations B Gene
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hypercholesterolemia
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
Collaborators: name: Sanofi
First posted: 2012-05-24
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

Inclusion criteria include, but are not limited to the following:

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

Exclusion Criteria:

Exclusion criteria include, but are not limited to the following:

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

Primary outcomes:
measure: Percent Change in Measured Serum Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 15
timeFrame: Baseline to Day 15
Secondary outcomes:
measure: Percent Change in Apolipoprotein (Apo) B100 From Baseline to Day 15
timeFrame: Baseline to Day 15
measure: Percent Change in Non High-Density Lipoprotein Cholesterol (Non-HDL-C) From Baseline to Day 15
timeFrame: Baseline to Day 15
measure: Percent Change in Total Cholesterol (Total-C) From Baseline to Day 15
timeFrame: Baseline to Day 15
measure: Percent Change in Apolipoprotein (Apo) B100/ ApoA-1 Ratio From Baseline to Day 15
timeFrame: Baseline to Day 15
Other outcomes:
Locations:
city: Salt Lake City
country: United States
state: Utah
city: Lille
country: France
state: Cedex
city: Nantes
country: France
state: Cedex
city: Paris
country: France
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.