Healthy Volunteers
Conditions
Brief summary
This is a randomized, 2-part, 2-arm, open-label, parallel-group, multi-center study to compare the PK of etrolizumab administered subcutaneously by an AI (test device) or a PFS-NSD (reference device) in healthy participants. The study will comprise a pilot cohort (Part 1) to estimate the geometric mean ratio (GMR) and variability of the maximum observed concentration (Cmax) and area under the concentration-time curve (AUC) to confirm or determine the sample size for the pivotal cohort (Part 2). The pivotal cohort will demonstrate exposure comparability of Cmax, AUC from Hour 0 to the last measurable concentration (AUClast), and AUC from Hour 0 to extrapolated infinite time (AUC0-inf), values for a single dose of etrolizumab administered subcutaneously either by the AI or the PFS-NSD.
Interventions
DRUGEtrolizumab
Etrolizumab will be administered at a dose of 105 milligrams (mg).
DEVICEAuto-Injector (AI)
The pre-filled AI will be used to administer etrolizumab.
DEVICEPrefilled Syringe With Needle Safety Device (PFS-NSD)
The PFS-NSD will be used to administer etrolizumab.
Sponsors
Genentech, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
HEALTH_SERVICES_RESEARCH
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Within the body weight range of 60 to 100 kilograms, inclusive (for the pivotal cohort \[Part 2\] only) * Within body mass index (BMI) range 18.0 to 30.0 kilograms per square meter (kg/m\^2), inclusive * In good health, determined by no clinically significant findings from medical history, physical examination, 12-lead electrocardiogram (ECG), and vital signs * Females will be non-pregnant, non-lactating, and either postmenopausal (at least 12 months of non-therapy-induced amenorrhea)/surgically sterile (e.g., tubal ligation, hysterectomy) for at least 90 days prior to enrolment, or agree to remain abstinent/use a highly effective method of contraception for at least 24 weeks after study drug administration * Males will either be sterile or agree to remain abstinent/use a highly effective method of contraception for at least 24 weeks after study drug administration. Male participants will refrain from sperm donation from Check-in (Day -1) until 24 weeks following study drug administration
Exclusion criteria
* Any prior treatment with etrolizumab or other anti-integrin agents (including natalizumab, vedolizumab, and efalizumab) * Any prior treatment with anti-mucosal addressin cell adhesion molecule 1 (anti-MAdCAM-1) agents * Any prior treatment with rituximab * Received intravenous corticosteroids within 30 days prior to Screening * Use of agents that deplete B or T cells (e.g., alemtuzumab, rituximab, or visilizumab) within 12 months prior to randomization * Any prior immunosuppressive agents (including cyclosporine, tacrolimus, sirolimus, mycophenolate mofetil) * Chronic nonsteroidal anti-inflammatory drug (NSAID) use * Use of any prescription medications/products within 14 days prior to Check in (Day -1) * History of demyelinating disease * Neurological conditions or diseases * History of cancer * History of alcoholism or drug addiction within less than (\<) 1 year prior to Screening * History of active or latent tuberculosis (TB), regardless of treatment history * History of recurrent opportunistic infections and/or history of severe disseminated viral infections * Positive for human immunodeficiency virus (HIV) antibody * Any current or recent signs or symptoms of infection * Pregnant or lactating * Hospitalized within 4 weeks prior to and during Screening * History of organ transplant * Presence of skin rash at Screening or history of other skin disorders * Tattoos, scars, chronic rashes, or sunburn in the area of the designated injection site
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Part 2: AUC0-inf of Etrolizumab | Predose (0 hours) and 6 hours postdose on Day 1, on Days 2, 4, 6, 8, 11, 15, 29, 43, 57, and at end of study (Day 71) or early discontinuation (up to Day 71) |
| Part 1: AUClast of Etrolizumab | Predose (0 hours) and 6 hours postdose on Day 1, on Days 2, 4, 6, 8, 11, 15, 29, 43, 57, and at end of study (Day 71) or early discontinuation (up to Day 71) |
| Part 1: Cmax of Etrolizumab | Predose (0 hours) and 6 hours postdose on Day 1, on Days 2, 4, 6, 8, 11, 15, 29, 43, 57, and at end of study (Day 71) or early discontinuation (up to Day 71) |
| Part 1: AUC0-inf of Etrolizumab | Predose (0 hours) and 6 hours postdose on Day 1, on Days 2, 4, 6, 8, 11, 15, 29, 43, 57, and at end of study (Day 71) or early discontinuation (up to Day 71) |
| Part 1: Ratio of AUClast to AUC0-inf (AUCR) of Etrolizumab | Predose (0 hours) and 6 hours postdose on Day 1, on Days 2, 4, 6, 8, 11, 15, 29, 43, 57, and at end of study (Day 71) or early discontinuation (up to Day 71) |
| Part 2: Cmax of Etrolizumab | Predose (0 hours) and 6 hours postdose on Day 1, on Days 2, 4, 6, 8, 11, 15, 29, 43, 57, and at end of study (Day 71) or early discontinuation (up to Day 71) |
| Part 2: AUClast of Etrolizumab | Predose (0 hours) and 6 hours postdose on Day 1, on Days 2, 4, 6, 8, 11, 15, 29, 43, 57, and at end of study (Day 71) or early discontinuation (up to Day 71) |
Secondary
| Measure | Time frame |
|---|---|
| Part 1: Time to Maximum Observed Concentration (tmax) of Etrolizumab | Predose (0 hours) and 6 hours postdose on Day 1, on Days 2, 4, 6, 8, 11, 15, 29, 43, 57, and at end of study (Day 71) or early discontinuation (up to Day 71) |
| Part 2: tmax of Etrolizumab | Predose (0 hours) and 6 hours postdose on Day 1, on Days 2, 4, 6, 8, 11, 15, 29, 43, 57, and at end of study (Day 71) or early discontinuation (up to Day 71) |
| Part 1: Apparent Terminal Elimination Half-Life (t1/2) of Etrolizumab | Predose (0 hours) and 6 hours postdose on Day 1, on Days 2, 4, 6, 8, 11, 15, 29, 43, 57, and at end of study (Day 71) or early discontinuation (up to Day 71) |
| Part 2: t1/2 of Etrolizumab | Predose (0 hours) and 6 hours postdose on Day 1, on Days 2, 4, 6, 8, 11, 15, 29, 43, 57, and at end of study (Day 71) or early discontinuation (up to Day 71) |
| Part 2: AUCR of Etrolizumab | Predose (0 hours) and 6 hours postdose on Day 1, on Days 2, 4, 6, 8, 11, 15, 29, 43, 57, and at end of study (Day 71) or early discontinuation (up to Day 71) |
| Percentage of Participants With Adverse Events | Part 1 and 2: Baseline up to Day 71 |
| Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) Against Etrolizumab | Part 1 and 2: Baseline up to Day 71 |
Countries
United States
Outcome results
None listed