Effect of Alirocumab on Lipid Metabolism in Adults With Elevated LDL-Cholesterol

A Phase 1 Study of the Effects of Subcutaneous Doses of Alirocumab on Lipid and Lipoprotein Metabolism in Adults With Mildly Elevated LDL-Cholesterol

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.

Study Overview

• Status: Completed
• Conditions: Hypercholesterolemia
• Intervention / Treatment: Drug: alirocumab; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • Investigational Site Number 840001

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Placebo - Alirocumab; Injection through subcutaneous (SC) administration, placebo for 4 weeks then, alirocumab for 10 weeks	Drug: alirocumab; Pharmaceutical form:Solution for injection Route of administration: Subcutaneous; Other Names: SAR236553; REGN727; Praluent; Drug: Placebo; Pharmaceutical form:Solution for injection Route of administration: Subcutaneous

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percent change in Fractional Clearance Rate of apolipoprotein B (apoB) in Low Density Lipoproteins (pools/day) in plasma during alirocumab treatment	baseline and at 12 days after last dose of alirocumab

Secondary Outcome Measures

Outcome Measure	Time Frame
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)	baseline and at 12 days after last dose of alirocumab
Change in post-heparin hepatic lipase and lipoprotein lipase activities	baseline and at 2 days after last dose of alirocumab
Change in lipids and apolipoproteins in plasma lipids panel	baseline and at 2 days and at 11 days after last dose of alirocumab
Assessment of Lipoprotein particle size profiles	baseline and at 2 days and at 11 days after last dose of alirocumab
Assessment of serum concentrations of PCSK9	baseline and up to 2 weeks after last dose of alirocumab
Assessment of safety parameters (clinical laboratory, ECG, vital signs)	up to 10 weeks after last dose of alirocumab
Assessment of the serum concentration of alirocumab	baseline and up to 2 weeks after last dose of alirocumab
Assessment of the serum concentration of anti-alirocumab antibodies	baseline and up to 10 weeks after last dose of alirocumab

Collaborators and Investigators

• Sponsor: Sanofi
• Collaborators: Regeneron Pharmaceuticals

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: December 1, 2013
• Primary Completion (Actual): May 1, 2015
• Study Completion (Actual): May 1, 2015

Study Registration Dates

• First Submitted: October 7, 2013
• First Submitted That Met QC Criteria: October 9, 2013
• First Posted (Estimate): October 10, 2013

Study Record Updates

• Last Update Posted (Actual): May 2, 2017
• Last Update Submitted That Met QC Criteria: April 28, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Hypercholesterolemia
• Other Study ID Numbers: PDY13670; U1111-1141-4567 (Other Identifier: UTN)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No