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

Primary Purpose

Hypercholesterolemia

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

alirocumab

Placebo

About this trial

This is an interventional basic science trial for Hypercholesterolemia

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

Investigational Site Number 840001

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Placebo - Alirocumab

Arm Description

Injection through subcutaneous (SC) administration, placebo for 4 weeks then, alirocumab for 10 weeks

Outcomes

Primary Outcome Measures

Percent change in Fractional Clearance Rate of apolipoprotein B (apoB) in Low Density Lipoproteins (pools/day) in plasma during alirocumab treatment

Secondary Outcome Measures

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)

Change in post-heparin hepatic lipase and lipoprotein lipase activities

Change in lipids and apolipoproteins in plasma lipids panel

Assessment of Lipoprotein particle size profiles

Assessment of serum concentrations of PCSK9

Assessment of safety parameters (clinical laboratory, ECG, vital signs)

Assessment of the serum concentration of alirocumab

Assessment of the serum concentration of anti-alirocumab antibodies

Full Information

NCT ID

NCT01959971

First Posted

October 7, 2013

Last Updated

April 28, 2017

Sponsor

Sanofi

Collaborators

Regeneron Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT01959971

Brief Title

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

2. Study Status

Record Verification Date

April 2017

Overall Recruitment Status

Completed

Study Start Date

December 2013 (undefined)

Primary Completion Date

May 2015 (Actual)

Study Completion Date

May 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Sanofi

Collaborators

Regeneron Pharmaceuticals

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hypercholesterolemia

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 1

Interventional Study Model

Crossover Assignment

Model Description

Single-sequence crossover

Masking

Participant

Enrollment

20 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Placebo - Alirocumab

Arm Type

Experimental

Arm Description

Injection through subcutaneous (SC) administration, placebo for 4 weeks then, alirocumab for 10 weeks

Intervention Type

Drug

Intervention Name(s)

alirocumab

Other Intervention Name(s)

SAR236553, REGN727, Praluent

Intervention Description

Pharmaceutical form:Solution for injection Route of administration: Subcutaneous

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Pharmaceutical form:Solution for injection Route of administration: Subcutaneous

Primary Outcome Measure Information:

Title

Percent change in Fractional Clearance Rate of apolipoprotein B (apoB) in Low Density Lipoproteins (pools/day) in plasma during alirocumab treatment

Time Frame

baseline and at 12 days after last dose of alirocumab

Secondary Outcome Measure Information:

Title

Time Frame

baseline and at 12 days after last dose of alirocumab

Title

Change in post-heparin hepatic lipase and lipoprotein lipase activities

Time Frame

baseline and at 2 days after last dose of alirocumab

Title

Change in lipids and apolipoproteins in plasma lipids panel

Time Frame

baseline and at 2 days and at 11 days after last dose of alirocumab

Title

Assessment of Lipoprotein particle size profiles

Time Frame

baseline and at 2 days and at 11 days after last dose of alirocumab

Title

Assessment of serum concentrations of PCSK9

Time Frame

baseline and up to 2 weeks after last dose of alirocumab

Title

Assessment of safety parameters (clinical laboratory, ECG, vital signs)

Time Frame

up to 10 weeks after last dose of alirocumab

Title

Assessment of the serum concentration of alirocumab

Time Frame

baseline and up to 2 weeks after last dose of alirocumab

Title

Assessment of the serum concentration of anti-alirocumab antibodies

Time Frame

baseline and up to 10 weeks after last dose of alirocumab

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Clinical Sciences & Operations

Organizational Affiliation

Sanofi

Official's Role

Study Director

Facility Information:

Facility Name

Investigational Site Number 840001

City

New York

State/Province

New York

ZIP/Postal Code

10032

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

27986651

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.

Results Reference

result

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

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