A Study to Compare Pharmacokinetics (PK) of Etrolizumab Administered Subcutaneously by a Prefilled Syringe With Needle Safety Device (PFS-NSD) or an Auto-injector (AI)
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Part 1: Etrolizumab AI Participants will receive a single dose of etrolizumab via subcutaneous (SC) injection using the AI on Day 1. |
Drug: Etrolizumab
Etrolizumab will be administered at a dose of 105 milligrams (mg).
Other Names:
Device: Auto-Injector (AI)
The pre-filled AI will be used to administer etrolizumab.
|
| Active Comparator: Part 1: Etrolizumab PFS-NSD Participants will receive a single dose of etrolizumab via SC injection using the PFS-NSD on Day 1. |
Drug: Etrolizumab
Etrolizumab will be administered at a dose of 105 milligrams (mg).
Other Names:
Device: Prefilled Syringe With Needle Safety Device (PFS-NSD)
The PFS-NSD will be used to administer etrolizumab.
|
| Experimental: Part 2: Etrolizumab AI Participants will receive a single dose of etrolizumab via SC injection using the AI on Day 1. |
Drug: Etrolizumab
Etrolizumab will be administered at a dose of 105 milligrams (mg).
Other Names:
Device: Auto-Injector (AI)
The pre-filled AI will be used to administer etrolizumab.
|
| Active Comparator: Part 2: Etrolizumab PFS-NSD Participants will receive a single dose of etrolizumab via SC injection using the PFS-NSD on Day 1. |
Drug: Etrolizumab
Etrolizumab will be administered at a dose of 105 milligrams (mg).
Other Names:
Device: Prefilled Syringe With Needle Safety Device (PFS-NSD)
The PFS-NSD will be used to administer etrolizumab.
|
Outcome Measures
Primary Outcome Measures
- 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: 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: 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)]
- 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)]
Secondary Outcome Measures
- 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]
Eligibility Criteria
Criteria
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)
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Any prior treatment with anti-mucosal addressin cell adhesion molecule 1 (anti-MAdCAM-1) agents
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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)
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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
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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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Covance Research Unit - Daytona | Daytona Beach | Florida | United States | 32117 |
| 2 | Covance Clinical Research Unit Inc.; Covance Gfi Research | Evansville | Indiana | United States | 47710 |
| 3 | Covance Research Unit - Dallas | Dallas | Texas | United States | 75247 |
| 4 | Covance Clinical Research Unit, Inc | Madison | Wisconsin | United States | 53704 |
Sponsors and Collaborators
- Genentech, Inc.
Investigators
- Study Director: Clinical Trials, Hoffmann-La Roche
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- GX29504