Clinical trial NCT02678988: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteer
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2016-02-10
Enrollment: 189
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Maximum observed serum concentration (Cmax) of TCZ
timeFrame: 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
measure: Area under the serum concentration-time curve from time zero to last quantifiable concentration (AUClast) of TCZ
timeFrame: 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:
measure: Area under the serum concentration-time curve from time zero to extrapolated infinite time [AUC (0-inf)] of TCZ
timeFrame: 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
measure: Time to reach maximum observed serum concentration (Tmax) of TCZ
timeFrame: 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
measure: Apparent elimination rate constant (Kel) of TCZ
timeFrame: 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
measure: Number of participants with adverse events
timeFrame: Baseline up to 8 weeks after the last dose of study drug (approximately 7 months)
measure: Number of participants with anti-drug antibody (ADA) response
timeFrame: Pre-dose on Days 1 and 43, and Day 85
Other outcomes:
Locations:
city: Lenexa
country: United States
state: Kansas
city: Marlton
country: United States
state: New Jersey
city: Salt Lake City
country: United States
state: Utah
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.