Healthy Volunteers
Conditions
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.
Interventions
DRUGEvinacumab
SC or IV administration of Evinacumab
DRUGPlacebo
Matching placebo
Sponsors
Regeneron Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion 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/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of Treatment Emergent Adverse Events (TEAEs) | Baseline up to week 31 |
| Severity of TEAEs | Baseline up to week 31 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PK parameters of evinacumab for geometric means of AUC computed from time zero to the end of a dosing interval (AUCtau) | Up to Week 31 | following the first dose for the multiple dose cohorts |
| 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 | Up to Week 31 | single dose cohort |
| Ratio of Japanese versus Caucasian populations for geometric means of AUCtau | Up to Week 31 | following the first dose for the multiple dose cohorts |
| 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 | — |
| Pharmacokinetic (PK) parameters of evinacumab for geometric means of maximum (or peak) serum concentration (Cmax) | 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 | — |
| Absolute change from baseline over time in the PD variable: high-sensitivity C-reactive protein [hs-CRP] | 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) | Up to Week 31 | single dose cohort |
Countries
United States
Outcome results
None listed