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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

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ClinicalTrials.gov Identifier: NCT02678988
Recruitment Status : Completed
First Posted : February 10, 2016
Last Update Posted : November 2, 2016
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

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
Healthy Volunteer Device: AI-1000 G2 Device: PFS-NSD Drug: Tocilizumab Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 189 participants
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Study Start Date : February 2016
Actual Primary Completion Date : June 2016
Actual Study Completion Date : June 2016

Resource links provided by the National Library of Medicine

Drug Information available for: Tocilizumab

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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: RO4877533; Actemra/RoActemra




Primary Outcome Measures :
  1. Maximum observed serum concentration (Cmax) of TCZ [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Pre-dose on Days 1 and 43, and Day 85 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02678988


Locations
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United States, Kansas
Lenexa, Kansas, United States, 66219
United States, New Jersey
Marlton, New Jersey, United States, 08053
United States, Utah
Salt Lake City, Utah, United States, 84106
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
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Study Director: Clinical Trials Hoffmann-La Roche
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT02678988    
Other Study ID Numbers: WA30003
First Posted: February 10, 2016    Key Record Dates
Last Update Posted: November 2, 2016
Last Verified: November 2016