Clinical trial NCT01959971: Effect of Alirocumab on Lipid Metabolism in Adults With Elevated LDL-Cholesterol
Official title: A Phase 1 Study of the Effects of Subcutaneous Doses of Alirocumab on Lipid and Lipoprotein Metabolism in Adults With Mildly Elevated LDL-Cholesterol
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hypercholesterolemia
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
Collaborators: name: Regeneron Pharmaceuticals
First posted: 2013-10-10
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Intervention model: CROSSOVER
Intervention model description: Single-sequence crossover
Primary purpose: BASIC_SCIENCE

Brief summary: Primary Objective:

To assess the effects of subcutaneous (SC) doses of alirocumab on the elimination (measured by Fractional Clearance Rate (FCR)) of apolipoprotein B (apoB) in low density lipoprotein (LDL) in adults with mildly elevated LDL-cholesterol (LDL-C).

Secondary Objectives:

To assess the effects of SC doses of alirocumab on:

* Various parameters of the metabolism and turnover in plasma of different lipoproteins
* Plasma lipids concentration: total cholesterol, high density lipoprotein cholesterol (HDL-C), triglycerides, low density lipoprotein cholesterol (LDL-C), apoB, lipoprotein(a) (Lp(a))
* Lipoprotein particle size profile
* PCSK9 (free and total) concentrations in serum To assess safety and tolerability of alirocumab. To assess emergence of anti-alirocumab antibodies. To document serum alirocumab concentrations.

Detailed description: Total duration of the study per subject is 26 weeks, including a screening period of ≤ 4 weeks, placebo treatment period of 4 weeks, alirocumab treatment period of 10 weeks, and a follow up period of 8 weeks.

Eligibility criteria: Inclusion criteria:

Generally healthy; LDL-C level in serum or plasma ≥ 100 mg/dL and \< 190 mg/dL at Screening.

Exclusion criteria:

* LDL-C ≥ 160 mg/dL at Screening if more than 2 major Coronary Heart Disease risk factors, as defined in National Cholesterol Education Program guidelines.
* Receiving treatment of any kind for hyperlipidemia within 6 weeks of enrollment.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Primary outcomes:
measure: Percent change in Fractional Clearance Rate of apolipoprotein B (apoB) in Low Density Lipoproteins (pools/day) in plasma during alirocumab treatment
timeFrame: baseline and at 12 days after last dose of alirocumab
Secondary outcomes:
measure: Change in lipids turnover parameters measured in isolated Very Low Density Lipoproteins (VLDL), Intermediate Density Lipoproteins (IDL), Low Density Lipoproteins (LDL) and High Density Lipoproteins (HDL)
timeFrame: baseline and at 12 days after last dose of alirocumab
measure: Change in post-heparin hepatic lipase and lipoprotein lipase activities
timeFrame: baseline and at 2 days after last dose of alirocumab
measure: Change in lipids and apolipoproteins in plasma lipids panel
timeFrame: baseline and at 2 days and at 11 days after last dose of alirocumab
measure: Assessment of Lipoprotein particle size profiles
timeFrame: baseline and at 2 days and at 11 days after last dose of alirocumab
measure: Assessment of serum concentrations of PCSK9
timeFrame: baseline and up to 2 weeks after last dose of alirocumab
measure: Assessment of safety parameters (clinical laboratory, ECG, vital signs)
timeFrame: up to 10 weeks after last dose of alirocumab
measure: Assessment of the serum concentration of alirocumab
timeFrame: baseline and up to 2 weeks after last dose of alirocumab
measure: Assessment of the serum concentration of anti-alirocumab antibodies
timeFrame: baseline and up to 10 weeks after last dose of alirocumab
Other outcomes:
Locations:
city: New York
country: United States
facility: Investigational Site Number 840001
state: New York
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
citation: Reyes-Soffer G, Pavlyha M, Ngai C, Thomas T, Holleran S, Ramakrishnan R, Karmally W, Nandakumar R, Fontanez N, Obunike J, Marcovina SM, Lichtenstein AH, Matthan NR, Matta J, Maroccia M, Becue F, Poitiers F, Swanson B, Cowan L, Sasiela WJ, Surks HK, Ginsberg HN. Effects of PCSK9 Inhibition With Alirocumab on Lipoprotein Metabolism in Healthy Humans. Circulation. 2017 Jan 24;135(4):352-362. doi: 10.1161/CIRCULATIONAHA.116.025253. Epub 2016 Dec 16.