A Study to Evaluate the Bioequivalence of Tocilizumab Following Subcutaneous Administration Via an Autoinjector (AI 1000-G2) Versus a Pre-Filled Syringe in Healthy Volunteers

NCT02678988 | Completed Phase 1

• 1 other identifier: WA30003
• Study Type: interventional
• Target: 189
• Locations: 1 country
• Sites: 3

Brief Summary

The study consists of an eligibility screening period, two study periods involving single doses of tocilizumab (TCZ) according to an open-label, randomized, two-period crossover design with an interval of 6 weeks between periods, and a 6 week follow-up period. Healthy participants will receive a single subcutaneous (SC) injection of TCZ via a pre-filled syringe-needle safety device (PFS-NSD) and a single injection via an autoinjector (AI). The total duration of the study is up to 16 weeks from screening to follow-up. After screening, eligible participants will be randomly assigned to one of the two possible treatment sequences (Sequence 1: AI-1000 G2 followed by PFS-NSD or Sequence 2: PFS-NSD followed by AI-1000 G2) and assigned to one of three injection sites (1: abdomen, 2: thigh, or 3: upper arm). All participant groups will receive a total of two TCZ administrations each.

Conditions

Healthy Volunteer

Outcome Measures

Primary Outcomes (2)

• Maximum observed serum concentration (Cmax) of TCZ

  Pre-dose and 8 hours post-dose on Day 1, and pre-dose on Days 2, 3, 4, 5, 6, 8, 10, 13, 16, 19, 22, 29, 36, pre-dose and 8 hours post-dose on Day 43, and pre-dose on Days 44, 45, 46, 47, 48, 50, 52, 55, 58, 61, 64, 71, 78 and 85

• Area under the serum concentration-time curve from time zero to last quantifiable concentration (AUClast) of TCZ

  Pre-dose and 8 hours post-dose on Day 1, and pre-dose on Days 2, 3, 4, 5, 6, 8, 10, 13, 16, 19, 22, 29, 36, pre-dose and 8 hours post-dose on Day 43, and pre-dose on Days 44, 45, 46, 47, 48, 50, 52, 55, 58, 61, 64, 71, 78 and 85

Secondary Outcomes (5)

• Area under the serum concentration-time curve from time zero to extrapolated infinite time [AUC (0-inf)] of TCZ

  Pre-dose and 8 hours post-dose on Day 1, and pre-dose on Days 2, 3, 4, 5, 6, 8, 10, 13, 16, 19, 22, 29, 36, pre-dose and 8 hours post-dose on Day 43, and pre-dose on Days 44, 45, 46, 47, 48, 50, 52, 55, 58, 61, 64, 71, 78 and 85

• Time to reach maximum observed serum concentration (Tmax) of TCZ

  Pre-dose and 8 hours post-dose on Day 1, and pre-dose on Days 2, 3, 4, 5, 6, 8, 10, 13, 16, 19, 22, 29, 36, pre-dose and 8 hours post-dose on Day 43, and pre-dose on Days 44, 45, 46, 47, 48, 50, 52, 55, 58, 61, 64, 71, 78 and 85

• Apparent elimination rate constant (Kel) of TCZ

  Pre-dose and 8 hours post-dose on Day 1, and pre-dose on Days 2, 3, 4, 5, 6, 8, 10, 13, 16, 19, 22, 29, 36, pre-dose and 8 hours post-dose on Day 43, and pre-dose on Days 44, 45, 46, 47, 48, 50, 52, 55, 58, 61, 64, 71, 78 and 85

• Number of participants with adverse events

  Baseline up to 8 weeks after the last dose of study drug (approximately 7 months)

• Number of participants with anti-drug antibody (ADA) response

  Pre-dose on Days 1 and 43, and Day 85

Study Arms (6)

A1: Tocilizumab AI followed by PFS-NSD in abdomen

EXPERIMENTAL

Participants will receive two single doses of 162 milligrams (mg) tocilizumab SC, first dose via AI on Day 1 (Period 1) followed by a washout period of 6 weeks, thereafter second dose via PFS-NSD on Day 43 (Period 2), in abdomen.

Device: AI-1000 G2; Device: PFS-NSD; Drug: Tocilizumab

A2: Tocilizumab AI followed by PFS-NSD in thigh

EXPERIMENTAL

Participants will receive two single doses of 162 mg tocilizumab SC, first dose via AI on Day 1 (Period 1) followed by a washout period of 6 weeks, thereafter second dose via PFS-NSD on Day 43 (Period 2) in thigh.

Device: AI-1000 G2; Device: PFS-NSD; Drug: Tocilizumab

A3: Tocilizumab AI followed by PFS-NSD in upper arm

EXPERIMENTAL

Participants will receive two single doses of 162 mg tocilizumab SC, first dose via AI on Day 1 (Period 1) followed by a washout period of 6 weeks, thereafter second dose via PFS-NSD on Day 43 (Period 2), in upper arm.

Device: AI-1000 G2; Device: PFS-NSD; Drug: Tocilizumab

B1: Tocilizumab PFS-NSD followed by AI in abdomen

EXPERIMENTAL

Participants will receive two single doses of 162 mg tocilizumab SC, first dose via PFS-NSD on Day 1 (Period 1) followed by a washout period of 6 weeks, thereafter second dose via AI on Day 43 (Period 2), in abdomen.

Device: AI-1000 G2; Device: PFS-NSD; Drug: Tocilizumab

B2: Tocilizumab PFS-NSD followed by AI in thigh

EXPERIMENTAL

Participants will receive two single doses of 162 mg tocilizumab SC, first dose via PFS-NSD on Day 1 (Period 1) followed by a washout period of 6 weeks, thereafter second dose via AI on Day 43 (Period 2), in thigh.

Device: AI-1000 G2; Device: PFS-NSD; Drug: Tocilizumab

B3: Tocilizumab PFS-NSD followed by AI in upper arm

EXPERIMENTAL

Participants will receive two single doses of 162 mg tocilizumab SC, first dose via PFS-NSD on Day 1 (Period 1) followed by a washout period of 6 weeks, thereafter second dose via AI on Day 43 (Period 2), in thigh.

Device: AI-1000 G2; Device: PFS-NSD; Drug: Tocilizumab

Interventions

AI-1000 G2 DEVICE

The device will contain TCZ (180 milligrams per milliliter \[mg/mL\]) SC formulation single dose of 0.9 mL that corresponds to 162 mg TCZ administered via PFS and assembled in the AI (AI-1000 G2).

A1: Tocilizumab AI followed by PFS-NSD in abdomen; A2: Tocilizumab AI followed by PFS-NSD in thigh; A3: Tocilizumab AI followed by PFS-NSD in upper arm; B1: Tocilizumab PFS-NSD followed by AI in abdomen; B2: Tocilizumab PFS-NSD followed by AI in thigh; B3: Tocilizumab PFS-NSD followed by AI in upper arm

PFS-NSD DEVICE

The device will contain TCZ (180 mg/mL) SC formulation single dose of 0.9 mL that corresponds to 162 mg TCZ administered via PFS-NSD.

A1: Tocilizumab AI followed by PFS-NSD in abdomen; A2: Tocilizumab AI followed by PFS-NSD in thigh; A3: Tocilizumab AI followed by PFS-NSD in upper arm; B1: Tocilizumab PFS-NSD followed by AI in abdomen; B2: Tocilizumab PFS-NSD followed by AI in thigh; B3: Tocilizumab PFS-NSD followed by AI in upper arm

Tocilizumab DRUG

Participants will receive two single doses of 162 mg tocilizumab SC on Day 1 (Period 1) and Day 43 (Period 2), with a washout period of 6 weeks between the periods.

Also known as: RO4877533; Actemra/RoActemra

A1: Tocilizumab AI followed by PFS-NSD in abdomen; A2: Tocilizumab AI followed by PFS-NSD in thigh; A3: Tocilizumab AI followed by PFS-NSD in upper arm; B1: Tocilizumab PFS-NSD followed by AI in abdomen; B2: Tocilizumab PFS-NSD followed by AI in thigh; B3: Tocilizumab PFS-NSD followed by AI in upper arm

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male participants and their partners of child-bearing potential must be willing to use two effective contraceptive methods
• Female participants must be either postmenopausal or surgically sterile
• Intact normal skin in the area for intended injection
• Body weight less than (\<) 150 kilograms (kg)
• Have no contraindications from the following: a detailed medical and surgical history, a complete physical examination, including vital signs, 12-lead electro cardio gram (ECG), hematology, blood chemistry, serology, and urinalysis

You may not qualify if:

• Participants with any known active current or history of recurrent Infectious disease
• Positive result on hepatitis B surface antigen, hepatitis C antibody, or human immunodeficiency virus-1 (HIV-1) and HIV-2 at screening
• A history of clinically significant gastrointestinal, renal, hepatic, cardiovascular, or allergic disease
• Evidence of malignant disease, or malignancies diagnosed within the previous 5 years
• Use of or being dependent within the last 12 months on any substances of abuse, including a relevant past history of alcohol abuse
• Participants with a history of, or currently active primary or secondary immunodeficiency
• Participants who smoke more than 10 cigarettes per day or equivalent in tobacco
• Clinically relevant deviation from normal in the physical examination, including vital signs
• Clinically relevant ECG abnormalities on screening
• Evidence of atrial fibrillation, atrial flutter, right or left bundle branch block, Wolf-Parkinson-White syndrome, or cardiac pacemaker or any other significant cardiac abnormalities
• Known allergy to TCZ or any other ingredient in the subcutaneous (SC) formulation
• History of severe allergic or anaphylactic reactions to human, humanized, or murine monoclonal antibodies
• Known coagulopathy
• Clinically significant abnormalities in laboratory test results
• Immunization with a live or attenuated vaccine is prohibited within 4 weeks prior to study drug administration

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (3)

Unknown Facility

Lenexa, Kansas, 66219, United States

Location

Unknown Facility

Marlton, New Jersey, 08053, United States

Location

Unknown Facility

Salt Lake City, Utah, 84106, United States

Location

Related Publications (1)

• Fettner S, Mela C, Wildenhahn F, Tavanti M, Wells C, Douglass W, Mallalieu NL. Evidence of bioequivalence and positive patient user handling of a tocilizumab autoinjector. Expert Opin Drug Deliv. 2019 May;16(5):551-561. doi: 10.1080/17425247.2019.1604678. Epub 2019 May 2.

  PMID: 31043095 DERIVED

MeSH Terms

Interventions

tocilizumab

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 8, 2016
• First Posted: February 10, 2016
• Study Start: February 1, 2016
• Primary Completion: June 1, 2016
• Study Completion: June 1, 2016
• Last Updated: November 2, 2016

Record last verified: 2016-11

Locations

US (3)