Clinical trial NCT02996019: 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)
Official title: A Randomized, Open-Label, 2-Part, 2-Arm, Parallel-Group, Single-Dose, Multi-Center Study in Healthy Subjects to Investigate the Comparability of Pharmacokinetics of Etrolizumab Administered Subcutaneously by a Prefilled Syringe With Needle Safety Device or an Auto-Injector
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2016-12-19
Enrollment: 180
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: HEALTH_SERVICES_RESEARCH

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.


Eligibility 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)
* 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

Primary outcomes:
measure: Part 1: Cmax of Etrolizumab
timeFrame: 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)
measure: Part 1: AUClast of Etrolizumab
timeFrame: 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)
measure: Part 1: AUC0-inf of Etrolizumab
timeFrame: 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)
measure: Part 1: Ratio of AUClast to AUC0-inf (AUCR) of Etrolizumab
timeFrame: 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)
measure: Part 2: Cmax of Etrolizumab
timeFrame: 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)
measure: Part 2: AUClast of Etrolizumab
timeFrame: 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)
measure: Part 2: AUC0-inf of Etrolizumab
timeFrame: 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 outcomes:
measure: Part 1: Time to Maximum Observed Concentration (tmax) of Etrolizumab
timeFrame: 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)
measure: Part 2: tmax of Etrolizumab
timeFrame: 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)
measure: Part 1: Apparent Terminal Elimination Half-Life (t1/2) of Etrolizumab
timeFrame: 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)
measure: Part 2: t1/2 of Etrolizumab
timeFrame: 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)
measure: Part 2: AUCR of Etrolizumab
timeFrame: 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)
measure: Percentage of Participants With Adverse Events
timeFrame: Part 1 and 2: Baseline up to Day 71
measure: Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) Against Etrolizumab
timeFrame: Part 1 and 2: Baseline up to Day 71
Other outcomes:
Locations:
city: Daytona Beach
country: United States
facility: Covance Research Unit - Daytona
state: Florida
city: Evansville
country: United States
facility: Covance Clinical Research Unit Inc.; Covance Gfi Research
state: Indiana
city: Dallas
country: United States
facility: Covance Research Unit - Dallas
state: Texas
city: Madison
country: United States
facility: Covance Clinical Research Unit, Inc
state: Wisconsin
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Zhang W, Tyrrell H, Ding HT, Pulley J, Boruvka A, Erickson R, Abouhossein M, Ravanello R, Tang MT. Comparable Pharmacokinetics, Safety, and Tolerability of Etrolizumab Administered by Prefilled Syringe or Autoinjector in a Randomized Trial in Healthy Volunteers. Adv Ther. 2021 May;38(5):2418-2434. doi: 10.1007/s12325-021-01661-6. Epub 2021 Mar 29.