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

Study Overview
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Brief Summary
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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.

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

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: Evinacumab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Healthy male or female Japanese and Caucasian volunteers ≥18 and ≤55 years of age at the screening visit. Japanese subjects must: Be first generation Japanese, defined as born in Japan and both biologic parents are ethnic Japanese 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 |