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

Healthy Volunteer Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02678988
• Other study ID #: WA30003
• Status: Completed
• Phase: Phase 1
• First received: February 8, 2016
• Last updated: November 1, 2016
• Start date: February 2016
• Est. completion date: June 2016

Study information

• Verified date: November 2016
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 189
• Est. completion date: June 2016
• Est. primary completion date: June 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Allocation: Non-Randomized, Endpoint Classification: Bio-equivalence Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Healthy Volunteer

Intervention

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).
• 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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	Number of participants with adverse events		Baseline up to 8 weeks after the last dose of study drug (approximately 7 months)	No
Secondary	Number of participants with anti-drug antibody (ADA) response		Pre-dose on Days 1 and 43, and Day 85	No