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

Roche

Status and phase: Completed; Phase 1

Conditions: Healthy Volunteer

Treatments: Device: AI-1000 G2; Device: PFS-NSD; Drug: Tocilizumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT02678988

WA30003

Details and patient eligibility

About

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.

Enrollment: 189 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

---

189 participants in 6 patient groups

A1: Tocilizumab AI followed by PFS-NSD in abdomen

Experimental group

Description:

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.

Treatment:

Drug: Tocilizumab

Device: PFS-NSD

Device: AI-1000 G2

A2: Tocilizumab AI followed by PFS-NSD in thigh

Experimental group

Description:

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.

Treatment:

Drug: Tocilizumab

Device: PFS-NSD

Device: AI-1000 G2

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

Experimental group

Description:

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.

Treatment:

Drug: Tocilizumab

Device: PFS-NSD

Device: AI-1000 G2

B1: Tocilizumab PFS-NSD followed by AI in abdomen

Experimental group

Description:

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.

Treatment:

Drug: Tocilizumab

Device: PFS-NSD

Device: AI-1000 G2

B2: Tocilizumab PFS-NSD followed by AI in thigh

Experimental group

Description:

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.

Treatment:

Drug: Tocilizumab

Device: PFS-NSD

Device: AI-1000 G2

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

Experimental group

Description:

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.

Treatment:

Drug: Tocilizumab

Device: PFS-NSD

Device: AI-1000 G2