A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Study Evaluating the Efficacy and Safety of Ustekinumab in the Treatment of Anti-TNF(Alpha) Refractory Subjects With Active Radiographic Axial Spondyloarthritis
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 315
- 主要终点
- Percentage of Participants Who Achieved an Assessment of SpondyloArthritis International Society (ASAS) 40 Response at Week 24
研究概览
简要总结
The purpose of this study is to assess the efficacy of ustekinumab, in adult anti-TNF(alpha) refractory participants with active radiographic axial spondyloarthritis (AxSpA), as measured by the reduction in signs and symptoms of radiographic AxSpA.
详细描述
This is a Phase 3, multicenter (when more than one hospital or medical school team work on a medical research study), randomized (study medication assigned to participants by chance), double-blind (neither the researchers nor the participants know what treatment the participant is receiving), placebo-controlled (an inactive substance; a pretend treatment [with no drug in it] that is compared in a clinical trial with a drug to test if the drug has a real effect) study. The study consists of 3 phases; Screening (up to 8 weeks), Treatment phase: placebo-controlled (Week 0 to 24) and active treatment (Week 24 to Week 52), and Safety Follow-up (up to 12 weeks). Participants will be randomly assigned to 1 of 3 treatment groups: placebo, ustekinumab 45 mg and ustekinumab 90 mg. The total duration of study will be up to 64 weeks. Participants will be primarily assessed for Assessment of SpondyloArthritis International Society (ASAS) 40 response at Week 24. Participants' safety will be monitored throughout the trial.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants must have a diagnosis of definite ankylosing spondylitis (AS), as defined by the modified 1984 New York criteria. The radiographic criterion must be confirmed by a central xray reader and at least 1 clinical criterion must be met
- •Participants must have symptoms of active disease at screening and at baseline, as evidenced by both a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score of greater than or equal to (>=4) and a visual analog scale (VAS) score for total back pain of >=4, each on a scale of 0 to 10
- •Participants with elevated high sensitivity C-reactive protein (hsCRP) level of >=0.300 milligram per deciliter (mg/dL) at screening
- •Refractory by either lack of benefit or documented intolerance to 1 and no more than 1 anti-TNF(alpha) agent
- •Inadequate response to at least 2 nonsteroidal anti-inflammatory drugs (NSAIDs) over a 4-week period in total with maximal doses of NSAID(s), or is unable to receive a full 4 weeks of maximal NSAID therapy because of intolerance, toxicity, or contraindications to NSAIDs.
- •Participants with complete ankylosis of the spine are permitted to be included in the study, but will be limited to approximately 10 percent (%) of the study population
排除标准
- •Participants who have other inflammatory diseases that might confound the evaluations of benefit from the ustekinumab therapy, including but not limited to, rheumatoid arthritis, systemic lupus erythematosus, or Lyme disease
- •Participants who have received infliximab or infliximab biosimilar, within 12 weeks of the first study agent administration; have received adalimumab, adalimumab biosimilar, or certolizumab pegol within 6 weeks of the first study agent administration; have received etanercept or etanercept biosimilar within 6 weeks of the first study agent administration
- •Participants who have ever received golimumab
- •Participants who are pregnant, nursing, or planning a pregnancy or fathering a child while enrolled in the study or within 5 months after receiving the last administration of study agent
- •Participants who have received any systemic immunosuppressives or disease-modifying antirheumatic drugs (DMARDs) other than methotrexate (MTX), sulfasalazine (SSZ), or hydroxychloroquine (HCQ) within 4 weeks prior to first administration of study agent. Medications in these categories include, but are not limited to leflunomide, chloroquine, azathioprine, cyclosporine, mycophenolate mofetil, gold, and penicillamine
研究组 & 干预措施
Group 1 (placebo)
Placebo subcutaneous (SC) injection at Weeks 0, 4, and 16. At Week 24 all participants (with the exception of participants who qualified for early escape [EE]) will be re-randomized to receive either ustekinumab 45 or 90 milligram (mg) SC injection at Weeks 24 and 28 followed by every 12 weeks (q12w) dosing, with the last administration of study agent at Week 52. Participants who meet EE criteria (less than [<] 10 percent [%] improvement from baseline in both total back pain and morning stiffness measures at both Week 12 and Week 16) will be administered open-label golimumab 50 mg SC administrations at Week 16 and every 4 weeks (q4w) thereafter through Week 52.
干预措施: Placebo (Drug)
Group 1 (placebo)
Placebo subcutaneous (SC) injection at Weeks 0, 4, and 16. At Week 24 all participants (with the exception of participants who qualified for early escape [EE]) will be re-randomized to receive either ustekinumab 45 or 90 milligram (mg) SC injection at Weeks 24 and 28 followed by every 12 weeks (q12w) dosing, with the last administration of study agent at Week 52. Participants who meet EE criteria (less than [<] 10 percent [%] improvement from baseline in both total back pain and morning stiffness measures at both Week 12 and Week 16) will be administered open-label golimumab 50 mg SC administrations at Week 16 and every 4 weeks (q4w) thereafter through Week 52.
干预措施: Ustekinumab 45 mg (Drug)
Group 1 (placebo)
Placebo subcutaneous (SC) injection at Weeks 0, 4, and 16. At Week 24 all participants (with the exception of participants who qualified for early escape [EE]) will be re-randomized to receive either ustekinumab 45 or 90 milligram (mg) SC injection at Weeks 24 and 28 followed by every 12 weeks (q12w) dosing, with the last administration of study agent at Week 52. Participants who meet EE criteria (less than [<] 10 percent [%] improvement from baseline in both total back pain and morning stiffness measures at both Week 12 and Week 16) will be administered open-label golimumab 50 mg SC administrations at Week 16 and every 4 weeks (q4w) thereafter through Week 52.
干预措施: Ustekinumab 90 mg (Drug)
Group 1 (placebo)
Placebo subcutaneous (SC) injection at Weeks 0, 4, and 16. At Week 24 all participants (with the exception of participants who qualified for early escape [EE]) will be re-randomized to receive either ustekinumab 45 or 90 milligram (mg) SC injection at Weeks 24 and 28 followed by every 12 weeks (q12w) dosing, with the last administration of study agent at Week 52. Participants who meet EE criteria (less than [<] 10 percent [%] improvement from baseline in both total back pain and morning stiffness measures at both Week 12 and Week 16) will be administered open-label golimumab 50 mg SC administrations at Week 16 and every 4 weeks (q4w) thereafter through Week 52.
干预措施: Golimumab 50 mg (Drug)
Group 2 (ustekinumab 45 mg)
Ustekinumab 45 mg SC injection at Weeks 0 and 4, followed by q12w dosing, with the last administration of study agent at Week 52. At Week 24, participants will receive placebo SC injection to maintain the blind. Participants who meet EE criteria (<10% improvement from baseline in both total back pain and morning stiffness measures at both Week 12 and Week 16) will be administered open-label golimumab 50 mg SC administrations at Week 16 and q4w thereafter through Week 52.
干预措施: Ustekinumab 45 mg (Drug)
Group 2 (ustekinumab 45 mg)
Ustekinumab 45 mg SC injection at Weeks 0 and 4, followed by q12w dosing, with the last administration of study agent at Week 52. At Week 24, participants will receive placebo SC injection to maintain the blind. Participants who meet EE criteria (<10% improvement from baseline in both total back pain and morning stiffness measures at both Week 12 and Week 16) will be administered open-label golimumab 50 mg SC administrations at Week 16 and q4w thereafter through Week 52.
干预措施: Golimumab 50 mg (Drug)
Group 3 (ustekinumab 90 mg)
Ustekinumab 90 mg SC injection at Weeks 0 and 4, followed by q12w dosing, with the last administration of study agent at Week 52. At Week 24, participants will receive placebo SC injection to maintain the blind. Participants who meet EE criteria (<10% improvement from baseline in both total back pain and morning stiffness measures at both Week 12 and Week 16) will be administered open-label golimumab 50 mg SC administrations at Week 16 and q4w thereafter through Week 52.
干预措施: Ustekinumab 90 mg (Drug)
Group 3 (ustekinumab 90 mg)
Ustekinumab 90 mg SC injection at Weeks 0 and 4, followed by q12w dosing, with the last administration of study agent at Week 52. At Week 24, participants will receive placebo SC injection to maintain the blind. Participants who meet EE criteria (<10% improvement from baseline in both total back pain and morning stiffness measures at both Week 12 and Week 16) will be administered open-label golimumab 50 mg SC administrations at Week 16 and q4w thereafter through Week 52.
干预措施: Golimumab 50 mg (Drug)
结局指标
主要结局
Percentage of Participants Who Achieved an Assessment of SpondyloArthritis International Society (ASAS) 40 Response at Week 24
时间窗: Week(W) 24
ASAS 40 defined as improvement from baseline of greater than or equal to (\>=) 40% and with an absolute improvement from baseline of at least 2 on 0 to10cm scale in at least 3 of following 4 domains: Patient's global assessment (0 to 10cm; 0=very well,10=very poor),total back pain (0 to 10cm; 0=no pain,10=most severe pain), BASFI(self-assessment represented as mean (0 to 10 cm; 0=easy to 10=impossible) of 10 questions, 8 of which relate to participant's functional anatomy and 2 relate to participant's ability to cope with everyday life), Inflammation (0 to 10cm;0=none,10=very severe); no worsening at all from baseline in remaining domain. ASAS40 response based on imputed data using treatment failure(consider non-responders at and after treatment failure),early escape rules(consider non-responder at Week 20 and 24),non-responder\[NRI(non responder imputation)\] (missing responses at post baseline visit imputed as non-responder).
次要结局
- Percentage of Participants Who Achieved an ASAS 20 Response at Week 24(Week 24)
- Percentage of Participants Who Achieved at Least a 50 Percent (%) Improvement From Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at Week 24(Week 24)
- Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) Total Score at Week 24(Baseline and Week 24)
- Percentage of Participants Who Achieved Ankylosing Spondylitis Disease Activity Score-C Reactive Protein (ASDAS-CRP) Inactive Disease (<1.3) at Week 24(Week 24)
- Change From Baseline in High Sensitivity C-Reactive Protein (hsCRP) Levels Through Week 24(Baseline, Week 4, 8, 12, 16, 20 and 24)
- Percentage of Participants With ASDAS (CRP) Inactive Disease (<1.3) at Week 4, 8, 12, 16 and 20(Week 4, 8, 12, 16 and 20)
- Percentage of Participants Who Achieved ASAS 20 Responses at Week 4, 8, 12, 16 and 20(Week 4, 8, 12, 16 and 20)
- Change From Baseline in BASFI Total Score at Week 4, 8, 12, 16 and 20(Baseline, Week 4, 8, 12, 16 and 20)
- Percentage of Participants Who Achieved ASAS 40 Responses at Week 4, 8, 12, 16 and 20(Week 4, 8, 12, 16 and 20)
- Percentage of Participants Who Achieved at Least a 50% Improvement From Baseline in BASDAI at Week 4, 8, 12, 16 and 20(Week 4, 8, 12, 16 and 20)