A Randomized, Parallel-Group, Phase I/III Study to Evaluate Efficacy, Pharmacokinetics and Safety Between Subcutaneous CT-P13 and Intravenous CT-P13 in Patients With Active Rheumatoid Arthritis
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Celltrion
- 入组人数
- 407
- 试验地点
- 2
- 主要终点
- Area Under the Concentration-time Curve (AUCτ) of Infliximab at Steady State (Part 1)
研究概览
简要总结
This is a Phase I/III Study to Evaluate Efficacy, Pharmacokinetics and Safety between CT-P13 SC and CT-P13 IV in Patients with Active Rheumatoid Arthritis (RA).
详细描述
A new subcutaneous infliximab formulation is developed by Celltrion, Inc. as an alternative to the intravenous regimen where subcutaneous infliximab injection typically takes less than 2 minutes. The availability of a subcutaneous formulation of infliximab would increase the treatment options available to patients, particularly those wishing to self-administer their therapy. This Phase I/III Study randomized, double-blinded (Part 2 only), multicenter, parallel-group study was designed to evaluate Efficacy, Pharmacokinetics and Safety between Subcutaneous CT-P13 and Intravenous CT-P13 in Patients with Active RA.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Part 1 was open label.
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient is male or female between 18 and 75 years old, inclusive.
- •Patient has a diagnosis of RA according to the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for at least 6 months
- •Patient has active disease as defined by the presence of 6 or more swollen joints (of 28 assessed), 6 or more tender joints (of 28 assessed) and serum C-reactive protein (CRP) concentration >0.6 mg/dL
- •Patient who completed at least 3 months of treatment of oral or parenteral dosing with Methotrexate between 12.5 to 25 mg/kg (between 10 to 25 mg/week in Korea) and on stable dosing with Methotrexate for at least 4 weeks prior to the first administration of the study drug.
排除标准
- •Patient who has previously received a biological agent for the treatment of RA and/or a TNFα inhibitor for the treatment of other disease
- •Patient who has allergies to any of the excipients of infliximab or any other murine and/or human proteins or patient with a hypersensitivity to immunoglobulin product
- •Patient who had current or past history of chronic infection with hepatitis C or human immunodeficiency virus (HIV)-1 or -2 or current infection with hepatitis B
- •Patient who had acute infection requiring oral antibiotics within 2 weeks or parenteral injection of antibiotics within 4 weeks prior to the first administration of the study drug, other serious infection within 6 months prior to the first administration of study drug or recurrent herpes zoster or other chronic or recurrent infection within 6 weeks prior to the first administration of the study drug.
- •Patient who had an indeterminate result for interferon-γ release assay (IGRA) or latent tuberculosis (TB) at Screening. For Part 2, if IGRA result was indeterminate at Screening, 1 retest was possible during the screening. If the repeated IGRA result was negative, the patient could be included in the study.
结局指标
主要结局
Area Under the Concentration-time Curve (AUCτ) of Infliximab at Steady State (Part 1)
时间窗: Weeks 22 (pre-dose to 216 hours post-dose), 24 (14 days after start of administration [SOA] at Week 22), 26 (pre-dose) and 28 (42 days after SOA at Week 22), and Week 30 (pre-dose)
For Part 1, the primary pharmacokinetic (PK) endpoint of the AUCτ (area under the concentration-time curve) at steady state between Week 22 and Week 30 was analyzed in patients who received all doses (full) of study drug up to Week 30 (prior to Week 30) in the PK population. All patients in SC cohorts were randomly assigned at Week 14 in a 1:1 ratio to either Group A or B for PK monitoring visit period (Week 22 and Week 30). Therefore, AUCτ was calculated at Week 22 for Cohort 1: CT-P13 IV 3 mg/kg, Weeks 22 and 26 for Group A of SC cohorts, and Weeks 24 and 28 for Group B of SC cohorts.
Change From Baseline of Disease Activity Score Using 28 Joint Counts (DAS28) (CRP) at Week 22 (Part 2)
时间窗: Week 22
For Part 2, the primary efficacy endpoint was to demonstrate that CT-P13 SC 120 mg is non-inferior to CT-P13 IV 3 mg/kg at Week 22, as determined by clinical response according to mean change from baseline in DAS28 (CRP) at Week 22, using Analysis of Covariance (ANCOVA). Change from baseline for ANCOVA was defined as decrease from baseline and calculated as (DAS28 \[CRP\] at baseline - DAS28 \[CRP\] at Week 22). DAS28 (CRP) was calculated using the following formula: DAS28 (CRP) equals(=) (0.56 multiplied by \[\*\] the square root \[√\] of TJC28 \[tender joint count\]) plus (+) (0.28 \* √ of SJC28 \[swollen joint count\]) + (0.36 \* the natural logarithm \[ln\](CRP \[mg/L\] + 1)) + (0.014 \* patient global disease activity \[GH\] on visual analogue assessment \[VAS\]) + 0.96. DAS28 (CRP) provides a number on a scale from 0 to 10 indicating the current activity of patients with RA. DAS28 (CRP) score above 5.1 indicates high disease activity, whereas DAS28 (CRP) score below 3.2 indicates low disease activity.
次要结局
- Mean Actual Value of Disease Activity Score Using 28 Joint Counts (DAS28 [CRP]) (Part 2)(Baseline, Week 2, Week 6, Week 14, Week 22, Week 30, and Week 54)
- Number of Patients Achieving Clinical Response According to American College of Rheumatology 20% Response (ACR20) (Part 2)(Week 2, Week 6, Week 14, Week 22, Week 30, and Week 54)
- Observed Trough Serum Concentration (Ctrough) of Infliximab (Part 2)(SC group: Weeks 0, 2, 12, 20, 22, 24, 26, 28, 36, 44, and 52; IV group: Weeks 0, 2, 6, 14, 22, 36, 44, and 52)
- Mean Actual Value in Serum CRP Concentration (Pharmacodynamic Parameter) (Part 2)(Baseline, Week 2, Week 6, Week 14, Week 22, Week 30, Week 38, Week 46, and Week 54)