A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Study Evaluating the Efficacy and Safety of Ustekinumab in the Treatment of Anti-TNF Alpha Naive Subjects With Active Radiographic Axial Spondyloarthritis
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 347
- 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 participants with active radiographic axial spondyloarthritis (AxSpA), who are naive to anti-TNF alpha agents, 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 100), and Safety Follow-up (12 weeks after last dose). 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 112 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 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
- •If using nonsteroidal anti-inflammatory drugs (NSAIDs) or other analgesics for AS, must be on a stable dose for at least 2 weeks prior to the first administration of study agent. If currently not using NSAIDs or other analgesics for AS, must not have received NSAIDs or other analgesics for AS for at least 2 weeks prior to the first administration of the study agent
- •A woman of childbearing potential must have a negative serum (beta-human chorionic gonadotropin [beta-hCG]) at screening and a negative urine pregnancy test at Week 0 before randomization
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 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 prior biologic therapy, including but not limited to anti-TNF alpha agents, tocilizumab, alefacept, efalizumab, natalizumab, abatacept, anakinra, ustekinumab, tidrakizumab or other anti-interleukin (IL) 23 biologics, brodalumab, secukinumab, ixekizumab, and B-cell depleting therapies
- •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 chloroquine, azathioprine, cyclosporine, mycophenolate mofetil, gold, and penicillamine
- •Participant who have received leflunomide within 3 months prior to the first administration of study agent (irrespective of undergoing a drug elimination procedure), or have received leflunomide within 12 months prior to the first administration of study agent and have not undergone a drug elimination procedure
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 100. 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 100. 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 100. 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 100. 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 every 12 week dosing, with the last administration of study agent at Week 100. 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: Placebo (Drug)
Group 2 (Ustekinumab 45 mg)
Ustekinumab 45 mg SC injection at Weeks 0 and 4, followed by every 12 week dosing, with the last administration of study agent at Week 100. 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 every 12 week dosing, with the last administration of study agent at Week 100. 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 100. 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: Placebo (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 100. 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 100. 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 24
ASAS 40 defined as improvement from baseline of greater than or equal to (\>=) 40 percent (%) and absolute improvement from baseline of at least 2 on 0 to 10 centimeter (cm) 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\[NRI\] (missing responses at post baseline visit imputed as non-responder).
次要结局
- Percentage of Participants Who Achieved an Assessment of Spondyloarthritis International Society (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)
- Change From Baseline in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) Total Score at Week 16 and 24(Baseline, Week 16 and 24)
- Change From Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) at Week 16 and 24(Baseline, Week 16 and 24)
- Change From Baseline in Ankylosing Spondylitis Quality of Life Questionnaire (ASQoL) Score at Week 16 and 24(Baseline, Week 16 and 24)
- Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score at Week 16 and 24(Baseline, Week 16 and 24)
- Change From Baseline in Short Form-(SF)-36 Physical Component Summary (PCS) and SF-36 Mental Component Summary (MCS) at Week 16 and 24(Baseline, Week 16 and 24)
- Change From Baseline in BASDAI Inflammation Score Through Week 24(Baseline, Week 4, 8, 12, 16, 20 and 24)
- Change From Baseline in Composite and Domain Scores of Medical Outcomes Study Sleep Scale (MOS-SS) at Week 16 and 24(Baseline, Week (W) 16 and 24)
- Change From Baseline in Composite and Domain Scores of Medical Outcomes Study Sleep Scale (MOS-SS)-Quantity of Sleep/Optimal Sleep at Week 16 and 24(Baseline, Week (W) 16 and 24)
- Percentage of Participants With at Least a 40% Improvement From Baseline in ASAS 40 Components at Week 24(Week 24)
- Change From Baseline in European Quality of Life 5 Dimension (EQ-5D) Visual Analog Scale (VAS) Score at Week 16 and 24(Baseline, Week 16 and 24)
- Percentage of Participants Who Achieved at Least 20%, 50%, 70% and 90% Improvement From Baseline in BASDAI Through Week 24(Baseline, Week 4, 8, 12, 16, 20 and 24)
- Change From Baseline in BASDAI Total Score Through Week 24(Baseline, Week 4, 8, 12, 16, 20 and 24)
- Percentage of Participants Who Achieved ASAS 40 Response at Week 4, 8, 12, 16 and 20(Week 4, 8, 12, 16 and 20)
- Percentage of Participants Who Achieved ASAS 20 Response at Week 4, 8, 12, 16 and 20(Week 4, 8, 12, 16 and 20)
- Percentage of Participants Who Achieved Assessment of Spondyloarthritis International Society (ASAS) Partial Remission Through Week 24(Baseline, Week 4, 8, 12, 16, 20 and 24)
- Percentage of Participants Who Achieved ASAS 5/6 Response at Week 16 and 24(Week 16 and 24)
- Change From Baseline in Ankylosing Spondylitis Disease Activity Score ASDAS (CRP) Total Score Through Week 24(Baseline, Week 4, 8, 12 ,16, 20 and 24)
- Percentage of Participants Who Achieved ASDAS (CRP) Inactive Disease (<1.3) at Week 4, 8, 12, 16 and 20(Week 4, 8, 12, 16, and 20)
- Percentage of Participants With ASDAS (CRP) Major Improvement (Decrease >=2.0) Through Week 24(Baseline, Week 4, 8, 12, 16, 20 and 24)
- Percentage of Participants Who Achieved ASDAS (CRP) Clinically Important Improvement (Decrease >=1.1) Through Week 24(Baseline, Week 4, 8, 12, 16, 20 and 24)
- Change From Baseline in BASFI at Week 4, 8, 12, 16 and 20(Baseline, Week 4, 8, 12, 16 and 20)
- Change From Baseline in Chest Expansion at Week 16 and 24(Baseline, Week 16 and 24)
- Change From Baseline in Total Back Pain (TBP) and Night Back Pain (NBP) Through Week 24(Baseline, Week 4, 8, 12, 16, 20 and 24)
- Change From Baseline in Patients Global Assessment of Disease Activity Through Week 24(Baseline, Week 4, 8, 12, 16, 20 and 24)
- Change From Baseline in EQ-5D Index Score at Week 16 and 24(Baseline, Week 16 and 24)
- Change From Baseline in Berlin Magnetic Resonance Imaging (MRI) Spine Score at Week 24(Baseline and Week 24)
- Change From Baseline in Percent Work Time Missed Due to AS (Assessed by Work Productivity and Activity Impairment Questionnaire - Specific Health Problem [WPAI-SHP]) Through Week 24(Baseline, Week 16 and 24)
- Change From Baseline in Percent Impairment While Working Due to AS (Assessed by WPAI-SHP) Through Week 24(Baseline, Week 16 and 24)
- Change From Baseline in Percent Overall Work Impairment Due to AS (Assessed by WPAI-SHP) Through Week 24(Baseline, Week 16 and 24)
- Change From Baseline in Percent Non-work Activity Impairment Due to AS (Assessed by WPAI-SHP) Through Week 24(Baseline, Week 16 and 24)