A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of ABBV-154 in Subjects With Moderately to Severely Active Rheumatoid Arthritis With Inadequate Response to Biologic and/or Targeted Synthetic Disease-Modifying Anti-Rheumatic Drugs (b/tsDMARDs)
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 473
- 试验地点
- 220
- 主要终点
- Achievement of 50% Improvement as Measured by American College of Rheumatology Response Criteria (ACR50) at Week 12
研究概览
简要总结
Rheumatoid Arthritis (RA) is an inflammatory disease of the joints causing pain, stiffness, swelling and loss of joint function. This study evaluated how safe and effective ABBV-154 is in participants treated for moderately to severely active RA. Adverse events and change in the disease activity were assessed.
ABBV-154 is an investigational drug being evaluated for the treatment of RA. Study doctors placed the participants in 1 of 5 treatment groups or arms; each arm received a different treatment. There was a 1 in 5 chance that participants were assigned to placebo. Participants 18-75 years of age with moderate to severe RA were enrolled. Around 425 participants were to be enrolled in the study at approximately 270 sites worldwide.
The study was comprised of a 12 week placebo-controlled period, a double-blind long term extension (LTE) period 1 of 66 weeks, a LTE period 2 of 104 weeks and a follow-up visit 70 days after the last dose of the study drug. In the LTE period 1, participants in the placebo group were re-randomized to receive ABBV-154 at 1 of 2 different doses SC every other week (EOW). Other participants remained on their previous dose and dosing regimen of ABBV-154.
There may have been a higher treatment burden for participants in this trial compared to their standard of care. Participants attended regular visits during the study at a hospital or clinic. The effect of the treatment was checked by medical assessments, blood tests, and side effects, and completing questionnaires.
详细描述
Participants were randomly assigned at a ratio of 1:1:1:1:1 to ABBV-154 at either 40 mg, 150 mg, 340 mg, subcutaneously (SC) EOW; 340 mg SC every 4 weeks (E4W); or placebo SC EOW. Randomization was stratified by baseline glucocorticoid (yes/no); number of prior failed biologic and/or targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs) (1; 2 or more); and prior anti-TNF failure (yes/no) and if yes, further stratification by prior adalimumab use (yes/no).
After 12 weeks, participants receiving placebo were re-randomized to receive ABBV-154 150 mg SC EOW or 340 mg SC EOW for the long-term extension (LTE) periods. At re-randomization, participants were stratified by baseline glucocorticoid use (yes/no) and prior adalimumab use (yes/no). Participants from the other dose groups were to continue with their respective dose and dosing regimen.
The primary analysis was conducted after all ongoing participants completed Week 12 or withdrew from the study. A final analysis was to be conducted after all participants completed LTE period 2 and a safety follow-up visit or withdrew from the study. The study was terminated before any participants entered LTE Period 2.
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)
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
- •Clinical diagnosis of rheumatoid arthritis(RA) with fulfillment of the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for RA.
- •Participant has >= 6 swollen joints (based on 66 joint count) and >=6 tender joints (based on 68 joint count) at baseline.
- •Participant must have had an inadequate response to at least one prior biologic and/or targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs) treatment for RA.
- •Participants must be on stable dose of methotrexate (MTX).
排除标准
- •Participant discontinued prior adalimumab therapy due to intolerability or toxicity.
研究组 & 干预措施
Dose A of ABBV-154
Participants in this group will receive dose A of ABBV-154 subcutaneously (SC) every other week (eow) for 12 weeks in the placebo-controlled period, 66 weeks in the long term extension (LTE) period 1 and 104 weeks in LTE period 2.
干预措施: ABBV-154 (Drug)
Dose B of ABBV-154
Participants in this group will receive dose B of ABBV-154 SC eow for 12 weeks in the placebo-controlled period, 66 weeks in the LTE period 1 and 104 weeks in LTE period 2.
干预措施: ABBV-154 (Drug)
Dose C of ABBV-154 EOW
Participants in this group will receive dose C of ABBV-154 SC eow for 12 weeks in the placebo-controlled period, 66 weeks in the LTE period 1 and 104 weeks in LTE period 2.
干预措施: ABBV-154 (Drug)
Dose C of ABBV-154 E4W
Participants in this group will receive dose C of ABBV-154 SC every 4 weeks (e4w) for 12 weeks in the placebo-controlled period, 66 weeks in the LTE period 1 and 104 weeks in LTE period 2.
干预措施: ABBV-154 (Drug)
Placebo
Participants in this group will receive placebo SC eow for 12 weeks in the placebo-controlled period and will be re-randomized in 1:1 ratio to receive ABBV-154 dose B or C respectively SC eow for 66 weeks in the LTE period 1 and 104 weeks in LTE period 2.
干预措施: ABBV-154 (Drug)
Placebo
Participants in this group will receive placebo SC eow for 12 weeks in the placebo-controlled period and will be re-randomized in 1:1 ratio to receive ABBV-154 dose B or C respectively SC eow for 66 weeks in the LTE period 1 and 104 weeks in LTE period 2.
干预措施: Placebo (Drug)
结局指标
主要结局
Achievement of 50% Improvement as Measured by American College of Rheumatology Response Criteria (ACR50) at Week 12
时间窗: Week 12
Participants who met the following 3 conditions for improvement from baseline were classified as meeting the ACR50 response criteria: 1. ≥ 50% improvement in 68-tender joint count; 2. ≥ 50% improvement in 66-swollen joint count; and 3. ≥ 50% improvement in at least 3 of the 5 following parameters: * Physician's Global Assessment of Disease Activity (NRS) * Patient's Global Assessment of Disease Activity (NRS) * Patient's Assessment of Pain (NRS) * Health Assessment Questionnaire - Disability Index (HAQ-DI) * High-sensitivity C-reactive protein (hsCRP).
次要结局
- Change From Baseline in Disease Activity Score (DAS) 28 (CRP) at Week 12(Baseline to Week 12)
- Change in Clinical Disease Activity Index (CDAI) at Week 12(Baseline to Week 12)
- Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response at Week 12(Week 12)
- Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response at Week 12(Week 12)
- Percentage of Participants Achieving Low Disease Activity (LDA) Defined by DAS28 (CRP) <= 3.2 at Week 12(Week 12)
- Percentage of Participants Achieving LDA Defined by CDAI <= 10 at Week 12(Week 12)
- Percentage of Participants Achieving Clinical Remission (CR) Defined by DAS28 (CRP) < 2.6 at Week 12(Week 12)
- Percentage of Participants Achieving CR Defined by CDAI <= 2.8 at Week 12(Week 12)
- Change From Baseline in the Health Assessment Questionnaire Disability Index (HAQ-DI) to Week 12(Baseline to Week 12)