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
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 189
- 主要终点
- Maximum observed serum concentration (Cmax) of TCZ
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
A1: Tocilizumab AI followed by PFS-NSD in abdomen
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.
干预措施: AI-1000 G2 (Device)
A1: Tocilizumab AI followed by PFS-NSD in abdomen
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.
干预措施: PFS-NSD (Device)
A1: Tocilizumab AI followed by PFS-NSD in abdomen
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.
干预措施: Tocilizumab (Drug)
A2: Tocilizumab AI followed by PFS-NSD in thigh
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.
干预措施: AI-1000 G2 (Device)
A2: Tocilizumab AI followed by PFS-NSD in thigh
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.
干预措施: PFS-NSD (Device)
A2: Tocilizumab AI followed by PFS-NSD in thigh
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.
干预措施: Tocilizumab (Drug)
A3: Tocilizumab AI followed by PFS-NSD in upper arm
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.
干预措施: AI-1000 G2 (Device)
A3: Tocilizumab AI followed by PFS-NSD in upper arm
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.
干预措施: PFS-NSD (Device)
A3: Tocilizumab AI followed by PFS-NSD in upper arm
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.
干预措施: Tocilizumab (Drug)
B1: Tocilizumab PFS-NSD followed by AI in abdomen
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.
干预措施: AI-1000 G2 (Device)
B1: Tocilizumab PFS-NSD followed by AI in abdomen
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.
干预措施: PFS-NSD (Device)
B1: Tocilizumab PFS-NSD followed by AI in abdomen
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.
干预措施: Tocilizumab (Drug)
B2: Tocilizumab PFS-NSD followed by AI in thigh
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.
干预措施: AI-1000 G2 (Device)
B2: Tocilizumab PFS-NSD followed by AI in thigh
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.
干预措施: PFS-NSD (Device)
B2: Tocilizumab PFS-NSD followed by AI in thigh
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.
干预措施: Tocilizumab (Drug)
B3: Tocilizumab PFS-NSD followed by AI in upper arm
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.
干预措施: AI-1000 G2 (Device)
B3: Tocilizumab PFS-NSD followed by AI in upper arm
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.
干预措施: PFS-NSD (Device)
B3: Tocilizumab PFS-NSD followed by AI in upper arm
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.
干预措施: Tocilizumab (Drug)
结局指标
主要结局
Maximum observed serum concentration (Cmax) of TCZ
时间窗: 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
时间窗: 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
次要结局
- 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)