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
Phase 1
Completed
- Conditions
- Healthy Volunteer
- Interventions
- Registration Number
- NCT02678988
- Lead Sponsor
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 189
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description A2: Tocilizumab AI followed by PFS-NSD in thigh AI-1000 G2 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. A1: Tocilizumab AI followed by PFS-NSD in abdomen AI-1000 G2 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. A1: Tocilizumab AI followed by PFS-NSD in abdomen PFS-NSD 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. A2: Tocilizumab AI followed by PFS-NSD in thigh PFS-NSD 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. A3: Tocilizumab AI followed by PFS-NSD in upper arm AI-1000 G2 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. B1: Tocilizumab PFS-NSD followed by AI in abdomen PFS-NSD 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. B2: Tocilizumab PFS-NSD followed by AI in thigh PFS-NSD 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. B1: Tocilizumab PFS-NSD followed by AI in abdomen AI-1000 G2 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. B2: Tocilizumab PFS-NSD followed by AI in thigh AI-1000 G2 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. A3: Tocilizumab AI followed by PFS-NSD in upper arm PFS-NSD 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. B3: Tocilizumab PFS-NSD followed by AI in upper arm AI-1000 G2 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. B3: Tocilizumab PFS-NSD followed by AI in upper arm PFS-NSD 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. A1: Tocilizumab AI followed by PFS-NSD in abdomen Tocilizumab 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. A2: Tocilizumab AI followed by PFS-NSD in thigh Tocilizumab 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. A3: Tocilizumab AI followed by PFS-NSD in upper arm Tocilizumab 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. B1: Tocilizumab PFS-NSD followed by AI in abdomen Tocilizumab 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. B2: Tocilizumab PFS-NSD followed by AI in thigh Tocilizumab 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. B3: Tocilizumab PFS-NSD followed by AI in upper arm Tocilizumab 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.
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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