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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

Sponsor
Hoffmann-La Roche (Industry)
Overall Status
Completed
CT.gov ID
NCT02678988
Collaborator
(none)
189
Enrollment
3
Locations
6
Arms
4
Duration (Months)
63
Patients Per Site
15.8
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 1

Study Design

Study Type:
Interventional
Actual Enrollment :
189 participants
Allocation:
Non-Randomized
Intervention Model:
Crossover Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Study Start Date :
Feb 1, 2016
Actual Primary Completion Date :
Jun 1, 2016
Actual Study Completion Date :
Jun 1, 2016

Arms and Interventions

Arm Intervention/Treatment
Experimental: A1: Tocilizumab AI followed by PFS-NSD in abdomen

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
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).

Device: PFS-NSD
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.

Drug: Tocilizumab
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.
Other Names:
  • RO4877533; Actemra/RoActemra

    		•
    Experimental: A2: Tocilizumab AI followed by PFS-NSD in thigh

    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
    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).

    Device: PFS-NSD
    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.

    Drug: Tocilizumab
    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.
    Other Names:
  • RO4877533; Actemra/RoActemra

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

    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
    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).

    Device: PFS-NSD
    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.

    Drug: Tocilizumab
    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.
    Other Names:
  • RO4877533; Actemra/RoActemra

    		•
    Experimental: B1: Tocilizumab PFS-NSD followed by AI in abdomen

    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
    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).

    Device: PFS-NSD
    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.

    Drug: Tocilizumab
    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.
    Other Names:
  • RO4877533; Actemra/RoActemra

    		•
    Experimental: B2: Tocilizumab PFS-NSD followed by AI in thigh

    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
    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).

    Device: PFS-NSD
    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.

    Drug: Tocilizumab
    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.
    Other Names:
  • RO4877533; Actemra/RoActemra

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

    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
    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).

    Device: PFS-NSD
    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.

    Drug: Tocilizumab
    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.
    Other Names:
  • RO4877533; Actemra/RoActemra

    		•

    Outcome Measures

    Primary Outcome Measures

    1. 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]

    2. 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 Outcome Measures

    1. 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]

    2. 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]

    3. 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]

    4. Number of participants with adverse events [Baseline up to 8 weeks after the last dose of study drug (approximately 7 months)]

    5. Number of participants with anti-drug antibody (ADA) response [Pre-dose on Days 1 and 43, and Day 85]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 65 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    Inclusion Criteria:

    • 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

    Exclusion Criteria:

    • 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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Lenexa Kansas United States 66219
    2 Marlton New Jersey United States 08053
    3 Salt Lake City Utah United States 84106

    Sponsors and Collaborators

    • Hoffmann-La Roche

    Investigators

    • Study Director: Clinical Trials, Hoffmann-La Roche

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Hoffmann-La Roche
    ClinicalTrials.gov Identifier:
    NCT02678988
    Other Study ID Numbers:
    • WA30003
    First Posted:
    Feb 10, 2016
    Last Update Posted:
    Nov 2, 2016
    Last Verified:
    Nov 1, 2016

    Study Results

    No Results Posted as of Nov 2, 2016