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

Hypercholesterolemia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01604824
• Other study ID #: R727-CL-1018
• Status: Completed
• Phase: Phase 2
• Start date: February 22, 2012
• Est. completion date: July 28, 2017

Study information

• Verified date: June 2020
• Source: Regeneron Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 23
• Est. completion date: July 28, 2017
• Est. primary completion date: June 2, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Hypercholesterolemia
• Hyperlipoproteinemia Type II

Intervention

Drug:
• Alirocumab
SC injection in the abdomen
• Placebo
SC injection in the abdomen

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Regeneron Pharmaceuticals	Sanofi

Countries where clinical trial is conducted

United States,  France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Percent Change in Apolipoprotein (Apo) B100 From Baseline to Day 15	Baseline adjusted LS means and standard errors were obtained using the same ANCOVA model as for primary endpoint specifying the treatment arm as the fixed effect and the parameter value as a covariate.	Baseline to Day 15
Secondary	Percent Change in Non High-Density Lipoprotein Cholesterol (Non-HDL-C) From Baseline to Day 15		Baseline to Day 15
Secondary	Percent Change in Total Cholesterol (Total-C) From Baseline to Day 15		Baseline to Day 15
Secondary	Percent Change in Apolipoprotein (Apo) B100/ ApoA-1 Ratio From Baseline to Day 15		Baseline to Day 15

External Links

•   Circ Cardiovasc Genet. 2015 Dec;8(6):823-31. doi: 10.1161/CIRCGENETICS.115.001129. Epub 2015 Sep 15