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)

NCT02996019 | Completed Phase 1

• 1 other identifier: GX29504
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 4

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.

Conditions

Healthy Volunteers

Outcome Measures

Primary Outcomes (7)

• 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 Outcomes (7)

• 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)

Study Arms (4)

Part 1: Etrolizumab AI

EXPERIMENTAL

Participants will receive a single dose of etrolizumab via subcutaneous (SC) injection using the AI on Day 1.

Drug: Etrolizumab; Device: Auto-Injector (AI)

Part 1: Etrolizumab PFS-NSD

ACTIVE COMPARATOR

Participants will receive a single dose of etrolizumab via SC injection using the PFS-NSD on Day 1.

Drug: Etrolizumab; Device: Prefilled Syringe With Needle Safety Device (PFS-NSD)

Part 2: Etrolizumab AI

EXPERIMENTAL

Participants will receive a single dose of etrolizumab via SC injection using the AI on Day 1.

Drug: Etrolizumab; Device: Auto-Injector (AI)

Part 2: Etrolizumab PFS-NSD

ACTIVE COMPARATOR

Participants will receive a single dose of etrolizumab via SC injection using the PFS-NSD on Day 1.

Drug: Etrolizumab; Device: Prefilled Syringe With Needle Safety Device (PFS-NSD)

Interventions

Etrolizumab DRUG

Etrolizumab will be administered at a dose of 105 milligrams (mg).

Also known as: RO5490261

Part 1: Etrolizumab AI; Part 1: Etrolizumab PFS-NSD; Part 2: Etrolizumab AI; Part 2: Etrolizumab PFS-NSD

Auto-Injector (AI) DEVICE

The pre-filled AI will be used to administer etrolizumab.

Part 1: Etrolizumab AI; Part 2: Etrolizumab AI

Prefilled Syringe With Needle Safety Device (PFS-NSD) DEVICE

The PFS-NSD will be used to administer etrolizumab.

Part 1: Etrolizumab PFS-NSD; Part 2: Etrolizumab PFS-NSD

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Genentech, Inc.: lead

Study Sites (4)

Covance Research Unit - Daytona

Daytona Beach, Florida, 32117, United States

Location

Covance Clinical Research Unit Inc.; Covance Gfi Research

Evansville, Indiana, 47710, United States

Location

Covance Research Unit - Dallas

Dallas, Texas, 75247, United States

Location

Covance Clinical Research Unit, Inc

Madison, Wisconsin, 53704, United States

Location

Related Publications (1)

• 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.

  PMID: 33778929 DERIVED

MeSH Terms

Interventions

etrolizumab

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 14, 2016
• First Posted: December 19, 2016
• Study Start: December 7, 2016
• Primary Completion: April 9, 2018
• Study Completion: April 9, 2018
• Last Updated: December 3, 2018

Record last verified: 2018-11

Locations

US (4)