A Multicenter Open-Label, Long-Term Extension Study of WA22762 and NA25220 to Evaluate Safety and Efficacy of Subcutaneous Tocilizumab in Patients With Moderate to Severe Rheumatoid Arthritis
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 218
- 主要终点
- Number of Participants With at Least One Serious Adverse Event (SAE)
研究概览
简要总结
This open-label extension study will evaluate the long-term safety and efficacy of SC TCZ in participants with moderate to severe RA who have completed the 97-week WA22762 (NCT01194414) or 96-week NA25220 (NCT01232569) core studies on SC or intravenous (IV) TCZ. Participants will receive TCZ 162 milligrams (mg) SC every week (QW) or every 2 weeks (Q2W) for up to 96 weeks.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Completed the 97-week WA22762 (NCT01194414) or 96-week NA25220 (NCT01232569) core study on SC or IV TCZ and, based on the Investigator's judgment, may continue to benefit from TCZ treatment in this study investigating the SC formulation
- •Receiving treatment on an outpatient basis
- •Females of childbearing potential and males with female partners of childbearing potential must agree to use reliable means of contraception as defined by protocol
排除标准
- •Premature withdrawal from WA22762 (NCT01194414) or NA25220 (NCT01232569) core studies for any reason
- •History of severe allergic or anaphylactic reactions to human, humanized, or murine monoclonal antibodies
- •Evidence of serious uncontrolled concomitant disease or disorder
- •Known active current or history of recurrent bacterial, viral, fungal, mycobacterial, or other infections
- •Any major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks of Screening or oral antibiotics within 2 weeks of Screening
- •History of or currently active primary or secondary immunodeficiency
- •Oral corticosteroids at greater than (>) 10 mg per day prednisone or equivalent, or non-steroidal anti-inflammatory drugs (NSAIDs) above the maximum recommended dose
- •Intra-articular or parenteral corticosteroids within 4 weeks prior to Baseline
- •Treatment with any investigational or commercially available biologic disease-modifying anti-rheumatic drug (DMARD) other than TCZ at any time between completion of the core study WA22762 (NCT01194414) or NA25220 (NCT01232569) and enrollment in the long-term extension study
- •Pregnant or breastfeeding women
- •History of alcohol, drug, or chemical abuse within 1 year prior to Screening
研究组 & 干预措施
SC TCZ QW
Participants who received IV TCZ in the previous trial will be switched to SC TCZ 162 mg QW, and those who received SC TCZ will continue at their same dosage of SC TCZ 162 mg QW. Tocilizumab will be given for an additional 96 weeks in this open-label extension study.
干预措施: Tocilizumab (Drug)
SC TCZ Q2W
Participants who received SC TCZ will continue at their same dosage of SC TCZ 162 mg Q2W. Tocilizumab will be given for an additional 96 weeks in this open-label extension study.
干预措施: Tocilizumab (Drug)
结局指标
主要结局
Number of Participants With at Least One Serious Adverse Event (SAE)
时间窗: From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall)
Adverse events (AEs) were monitored throughout treatment. AEs were defined as any untoward medical occurrence in a participant who received study drug regardless of causality. SAEs were defined as AEs that were fatal or life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, manifested as a congenital anomaly/birth defect, were medically significant, or required intervention to prevent any of the aforementioned outcomes. The number of participants with at least one SAE regardless of treatment relationship was reported.
Percentage of Participants With a Positive Anti-TCZ Antibody Assay at Baseline
时间窗: Baseline
Blood samples were collected to test for the presence of antibodies to TCZ. The percentage of participants with a positive anti-TCZ antibody assay was calculated.
Percentage of Participants With a Positive Anti-TCZ Antibody Assay Post-Baseline
时间窗: From Week 12 up to 8 weeks after last dose; assessed at Weeks 12, 24, 36, 48, 60, 72, 84, 96; and up to 8 weeks after last dose (up to 2 years overall)
Blood samples were collected to test for the presence of antibodies to TCZ. The percentage of participants with a positive anti-TCZ antibody assay was calculated. Positive assay results obtained post-Baseline were further investigated via confirmation assay and a neutralization assay.
Percentage of Participants With at Least One SAE
时间窗: From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall)
AEs were monitored throughout treatment. AEs were defined as any untoward medical occurrence in a participant who received study drug regardless of causality. SAEs were defined as AEs that were fatal or life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, manifested as a congenital anomaly/birth defect, were medically significant, or required intervention to prevent any of the aforementioned outcomes. The percentage of participants with at least one SAE regardless of treatment relationship was calculated.
Percentage of Participants With a Positive Anti-TCZ Antibody Assay at Any Timepoint
时间窗: From Baseline to 8 weeks after last dose; assessed at Baseline; Weeks 12, 24, 36, 48, 60, 72, 84, 96; and up to 8 weeks after last dose (up to 2 years overall)
Blood samples were collected to test for the presence of antibodies to TCZ. The percentage of participants with a positive anti-TCZ antibody assay was calculated.
次要结局
- Change From Baseline in DAS28 Score(Baseline to Weeks 12, 24, 36, 48, 60, 72, 84)
- Clinical Disease Activity Index (CDAI) Score(Baseline and Weeks 12, 24, 36, 48, 60, 72, 84)
- Percentage of Participants Who Correctly Administered All SC TCZ Doses(From Baseline to last dose; assessed every 4 weeks during treatment (up to 96 weeks overall))
- Disease Activity Score Based on 28 Joints (DAS28) Score(Baseline and Weeks 12, 24, 36, 48, 60, 72, 84)
- Change From Baseline in CDAI Score(Baseline to Weeks 12, 24, 36, 48, 60, 72, 84)
- Simplified Disease Activity Index (SDAI) Score(Baseline and Weeks 12, 24, 36, 48, 60, 72, 84)
- Change From Baseline in SDAI Score(Baseline to Weeks 12, 24, 36, 48, 60, 72, 84)
- Tender Joint Count (TJC) Score(Baseline and Weeks 12, 24, 36, 48, 60, 72, 84)
- Change From Baseline in TJC Score(Baseline to Weeks 12, 24, 36, 48, 60, 72, 84)
- Change From Baseline in SJC Score(Baseline to Weeks 12, 24, 36, 48, 60, 72, 84)
- Percentage of Reasons Given for DMARD Discontinuation(From Baseline to last dose; assessed every 4 weeks during treatment (up to 96 weeks overall))
- Global Assessment of Disease Activity by the Participant According to Visual Analog Scale (VAS) Score(Baseline and Weeks 12, 24, 36, 48, 60, 72, 84)
- Swollen Joint Count (SJC) Score(Baseline and Weeks 12, 24, 36, 48, 60, 72, 84)
- Number of Participants With a Disease-Modifying Anti-Rheumatic Drug (DMARD) Dose Reduction, Interruption, or Discontinuation(From Baseline to last dose; assessed every 4 weeks during treatment (up to 96 weeks overall))
- Percentage of Participants With a DMARD Dose Reduction, Interruption, or Discontinuation(From Baseline to last dose; assessed every 4 weeks during treatment (up to 96 weeks overall))
- Percentage of Reasons Given for DMARD Dose Reduction or Interruption(From Baseline to last dose; assessed every 4 weeks during treatment (up to 96 weeks overall))
- Number of Participants With a Corticosteroid (CCS) Dose Reduction, Interruption, or Discontinuation(From Baseline to last dose; assessed every 4 weeks during treatment (up to 96 weeks overall))
- Percentage of Participants With a CCS Dose Reduction, Interruption, or Discontinuation(From Baseline to last dose; assessed every 4 weeks during treatment (up to 96 weeks overall))
- Percentage of Reasons Given for CCS Dose Reduction(From Baseline to last dose; assessed every 4 weeks during treatment (up to 96 weeks overall))
- Percentage of Reasons Given for CCS Dose Interruption(From Baseline to last dose; assessed every 4 weeks during treatment (up to 96 weeks overall))
- Number of Participants Who Returned to the QW Regimen After Switching to the Q2W Regimen(From Baseline to last dose; assessed every 4 weeks during treatment (up to 96 weeks overall))
- Change From Baseline in Global Assessment of Pain by the Participant According to VAS Score(Baseline to Weeks 12, 24, 36, 48, 60, 72, 84)
- Number of Participants With Low Disease Activity According to DAS28, SDAI, and CDAI Criteria(Baseline and Weeks 12, 24, 36, 48, 60, 72, 84)
- Time to Return to the QW Regimen After Switching to the Q2W Regimen(From Baseline to last dose; assessed every 4 weeks during treatment (up to 96 weeks overall))
- Percentage of Reasons Given for CCS Discontinuation(From Baseline to last dose; assessed every 4 weeks during treatment (up to 96 weeks overall))
- Number of Participants Who Switched From the QW Regimen and Remained on the Q2W Regimen(From Baseline to last dose; assessed every 4 weeks during treatment (up to 96 weeks overall))
- Percentage of Participants Who Switched From the QW Regimen and Remained on the Q2W Regimen(From Baseline to last dose; assessed every 4 weeks during treatment (up to 96 weeks overall))
- Change From Baseline in Global Assessment of Disease Activity by the Participant According to VAS Score(Baseline to Weeks 12, 24, 36, 48, 60, 72, 84)
- Percentage of Participants With HAQ-DI Score <0.5(Baseline and Weeks 12, 24, 36, 48, 60, 72, 84)
- Global Assessment of Pain by the Participant According to VAS Score(Baseline and Weeks 12, 24, 36, 48, 60, 72, 84)
- Percentage of Participants With Low Disease Activity According to DAS28, SDAI, and CDAI Criteria(Baseline and Weeks 12, 24, 36, 48, 60, 72, 84)
- Percentage of Participants With Remission According to DAS28, SDAI, and Boolean Criteria(Baseline and Weeks 12, 24, 36, 48, 60, 72, 84)
- Heath Assessment Questionnaire-Disability Index (HAQ-DI) Score(Baseline and Weeks 12, 24, 36, 48, 60, 72, 84)
- Change From Baseline in HAQ-DI Score(Baseline to Weeks 12, 24, 36, 48, 60, 72, 84)
- Number of Participants With Remission According to DAS28, SDAI, and Boolean Criteria(Baseline and Weeks 12, 24, 36, 48, 60, 72, 84)