Study of Evinacumab (REGN1500) in Caucasian and in Japanese Healthy Volunteers

A Randomized, Double-Blind, Placebo-Controlled Study to Investigate the Safety, Tolerability and Pharmacokinetics of Evinacumab in Healthy Japanese and Caucasian Subjects

The primary objective of the study is to compare the safety and tolerability of subcutaneous (SC) and intravenous (IV) doses of evinacumab in healthy Japanese and Caucasian subjects.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: Placebo; Drug: Evinacumab

• Study Type: Interventional
• Enrollment (Actual): 96
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Cypress, California, United States, 90630
      • WCCT Global, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 51 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

• Healthy male or female Japanese and Caucasian volunteers ≥18 and ≤55 years of age at the screening visit.

• Japanese subjects must:

  1. Be first generation Japanese, defined as born in Japan and both biologic parents are ethnic Japanese
  2. Have maintained a Japanese lifestyle that has not significantly changed since leaving Japan, including having access to Japanese food and adhering to a Japanese diet.
• Caucasian subjects must be Caucasian of European or Latin American descent
• Modest elevations in LDL-C (≥100 mg/dL, but <160 mg/dL)

Key Exclusion Criteria:

• Significant concomitant illness
• Known allergy or sensitivity to monoclonal antibodies (mAbs)
• Previous exposure to anti-ANGPTL3 antibody
• Body mass index (BMI) >35 kg/m2 at the screening visit

Note: Other protocol-defined inclusion/exclusion criteria apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Triple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; Evinacumab SC or placebo SC	Drug: Placebo; Matching placebo; Drug: Evinacumab; SC or IV administration of Evinacumab; Other Names: REGN1500
Experimental: Cohort 2; Low dose regimen: evinacumab IV or placebo IV	Drug: Placebo; Matching placebo; Drug: Evinacumab; SC or IV administration of Evinacumab; Other Names: REGN1500
Experimental: Cohort 3; High dose regimen: evinacumab IV or placebo IV	Drug: Placebo; Matching placebo; Drug: Evinacumab; SC or IV administration of Evinacumab; Other Names: REGN1500
Experimental: Cohort 4; Evinacumab or placebo SC every week (QW) x 8 doses	Drug: Placebo; Matching placebo; Drug: Evinacumab; SC or IV administration of Evinacumab; Other Names: REGN1500
Experimental: Cohort 5; Evinacumab or placebo SC x 1 dose	Drug: Placebo; Matching placebo; Drug: Evinacumab; SC or IV administration of Evinacumab; Other Names: REGN1500

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of Treatment Emergent Adverse Events (TEAEs)	Baseline up to week 31
Severity of TEAEs	Baseline up to week 31

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic (PK) parameters of evinacumab for geometric means of maximum (or peak) serum concentration (Cmax)		Up to Week 31
PK parameters of evinacumab for geometric means of Area under the curve (AUC) computed from time zero to the last measurable concentration (AUClast)	single dose cohort	Up to Week 31
PK parameters of evinacumab for geometric means of AUC computed from time zero to the end of a dosing interval (AUCtau)	following the first dose for the multiple dose cohorts	Up to Week 31
Ratio of Japanese versus Caucasian populations for geometric means of Cmax		Up to Week 31
Ratio of Japanese versus Caucasian populations for geometric means of AUClast	single dose cohort	Up to Week 31
Ratio of Japanese versus Caucasian populations for geometric means of AUCtau	following the first dose for the multiple dose cohorts	Up to Week 31
Absolute change from baseline over time in the Pharmacodynamic (PD) variable: Low-density lipoprotein cholesterol (LDL-C)		Up to Week 31
Absolute change from baseline over time in the PD variable: Total cholesterol		Up to Week 31
Absolute change from baseline over time in the PD variable: High-density lipoprotein cholesterol (HDL-C)		Up to Week 31
Absolute change from baseline over time in the PD variable: Triglycerides		Up to Week 31
Absolute change from baseline over time in the PD variable: non-HDL-C		Up to Week 31
Absolute change from baseline over time in the PD variable: lipoprotein a [Lp(a)]		Up to Week 31
Absolute change from baseline over time in the PD variable: apolipoprotein B [ApoB]		Up to Week 31
Absolute change from baseline over time in the PD variable: apolipoprotein A1 [ApoA1]		Up to Week 31
Absolute change from baseline over time in the PD variable: apolipoprotein C3 [ApoC3]		Up to Week 31
Absolute change from baseline over time in the PD variable: high-sensitivity C-reactive protein [hs-CRP]		Up to Week 31
Absolute change from baseline over time in the PD variable: Total Angiopoietin-like 3 (ANGPTL3)		Up to Week 31
Percent change from baseline over time in the PD variable: LDL-C		Up to Week 31
Percent change from baseline over time in the PD variable: Total cholesterol		Up to Week 31
Percent change from baseline over time in the PD variable: HDL-C		Up to Week 31
Percent change from baseline over time in the PD variable: Triglycerides		Up to Week 31
Percent change from baseline over time in the PD variable: non-HDL-C		Up to Week 31
Percent change from baseline over time in the PD variable: lipoprotein a [Lp(a)]		Up to Week 31
Percent change from baseline over time in the PD variable: apolipoprotein B [ApoB]		Up to Week 31
Percent change from baseline over time in the PD variable: apolipoprotein A1 [ApoA1]		Up to Week 31
Percent change from baseline over time in the PD variable: apolipoprotein C3 [ApoC3]		Up to Week 31
Percent change from baseline over time in the PD variable: high-sensitivity C-reactive protein [hs-CRP]		Up to Week 31
Percent change from baseline over time in the PD variable: Total (ANGPTL3)		Up to Week 31
Presence and titer of anti-evinacumab antibodies		Up to Week 31

Collaborators and Investigators

• Sponsor: Regeneron Pharmaceuticals

Publications and helpful links

General Publications

• Harada-Shiba M, Ali S, Gipe DA, Gasparino E, Son V, Zhang Y, Pordy R, Catapano AL. A randomized study investigating the safety, tolerability, and pharmacokinetics of evinacumab, an ANGPTL3 inhibitor, in healthy Japanese and Caucasian subjects. Atherosclerosis. 2020 Dec;314:33-40. doi: 10.1016/j.atherosclerosis.2020.10.013. Epub 2020 Oct 10.

Study record dates

Study Major Dates

• Study Start (Actual): May 16, 2017
• Primary Completion (Actual): June 14, 2018
• Study Completion (Actual): June 14, 2018

Study Registration Dates

• First Submitted: May 7, 2017
• First Submitted That Met QC Criteria: May 7, 2017
• First Posted (Actual): May 10, 2017

Study Record Updates

• Last Update Posted (Actual): June 25, 2018
• Last Update Submitted That Met QC Criteria: June 21, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Other Study ID Numbers: R1500-CL-1642

Drug and device information, study documents

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