Healthy Volunteer
Conditions
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.
Interventions
DEVICEAI-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).
DEVICEPFS-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.
DRUGTocilizumab
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.
Sponsors
Hoffmann-La Roche
Study design
Allocation
NON_RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame |
|---|---|
| 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 |
| 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 |
| Number of participants with anti-drug antibody (ADA) response | Pre-dose on Days 1 and 43, and Day 85 |
| Number of participants with adverse events | Baseline up to 8 weeks after the last dose of study drug (approximately 7 months) |
| 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 |
Countries
United States
Outcome results
None listed