Clinical trial NCT03146416: Study of Evinacumab (REGN1500) in Caucasian and in Japanese Healthy Volunteers
Official title: A Randomized, Double-Blind, Placebo-Controlled Study to Investigate the Safety, Tolerability and Pharmacokinetics of Evinacumab in Healthy Japanese and Caucasian Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2017-05-10
Enrollment: 96
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: BASIC_SCIENCE

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Incidence of Treatment Emergent Adverse Events (TEAEs)
timeFrame: Baseline up to week 31
measure: Severity of TEAEs
timeFrame: Baseline up to week 31
Secondary outcomes:
measure: Pharmacokinetic (PK) parameters of evinacumab for geometric means of maximum (or peak) serum concentration (Cmax)
timeFrame: Up to Week 31
measure: PK parameters of evinacumab for geometric means of Area under the curve (AUC) computed from time zero to the last measurable concentration (AUClast)
timeFrame: Up to Week 31
measure: PK parameters of evinacumab for geometric means of AUC computed from time zero to the end of a dosing interval (AUCtau)
timeFrame: Up to Week 31
measure: Ratio of Japanese versus Caucasian populations for geometric means of Cmax
timeFrame: Up to Week 31
measure: Ratio of Japanese versus Caucasian populations for geometric means of AUClast
timeFrame: Up to Week 31
measure: Ratio of Japanese versus Caucasian populations for geometric means of AUCtau
timeFrame: Up to Week 31
measure: Absolute change from baseline over time in the Pharmacodynamic (PD) variable: Low-density lipoprotein cholesterol (LDL-C)
timeFrame: Up to Week 31
measure: Absolute change from baseline over time in the PD variable: Total cholesterol
timeFrame: Up to Week 31
measure: Absolute change from baseline over time in the PD variable: High-density lipoprotein cholesterol (HDL-C)
timeFrame: Up to Week 31
measure: Absolute change from baseline over time in the PD variable: Triglycerides
timeFrame: Up to Week 31
measure: Absolute change from baseline over time in the PD variable: non-HDL-C
timeFrame: Up to Week 31
measure: Absolute change from baseline over time in the PD variable: lipoprotein a [Lp(a)]
timeFrame: Up to Week 31
measure: Absolute change from baseline over time in the PD variable: apolipoprotein B [ApoB]
timeFrame: Up to Week 31
measure: Absolute change from baseline over time in the PD variable: apolipoprotein A1 [ApoA1]
timeFrame: Up to Week 31
measure: Absolute change from baseline over time in the PD variable: apolipoprotein C3 [ApoC3]
timeFrame: Up to Week 31
measure: Absolute change from baseline over time in the PD variable: high-sensitivity C-reactive protein [hs-CRP]
timeFrame: Up to Week 31
measure: Absolute change from baseline over time in the PD variable: Total Angiopoietin-like 3 (ANGPTL3)
timeFrame: Up to Week 31
measure: Percent change from baseline over time in the PD variable: LDL-C
timeFrame: Up to Week 31
measure: Percent change from baseline over time in the PD variable: Total cholesterol
timeFrame: Up to Week 31
measure: Percent change from baseline over time in the PD variable: HDL-C
timeFrame: Up to Week 31
measure: Percent change from baseline over time in the PD variable: Triglycerides
timeFrame: Up to Week 31
measure: Percent change from baseline over time in the PD variable: non-HDL-C
timeFrame: Up to Week 31
measure: Percent change from baseline over time in the PD variable: lipoprotein a [Lp(a)]
timeFrame: Up to Week 31
measure: Percent change from baseline over time in the PD variable: apolipoprotein B [ApoB]
timeFrame: Up to Week 31
measure: Percent change from baseline over time in the PD variable: apolipoprotein A1 [ApoA1]
timeFrame: Up to Week 31
measure: Percent change from baseline over time in the PD variable: apolipoprotein C3 [ApoC3]
timeFrame: Up to Week 31
measure: Percent change from baseline over time in the PD variable: high-sensitivity C-reactive protein [hs-CRP]
timeFrame: Up to Week 31
measure: Percent change from baseline over time in the PD variable: Total (ANGPTL3)
timeFrame: Up to Week 31
measure: Presence and titer of anti-evinacumab antibodies
timeFrame: Up to Week 31
Other outcomes:
Locations:
city: Cypress
country: United States
facility: WCCT Global, Inc.
state: California
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References:
citation: 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.