A Phase 2a, Multicenter, Randomized, Double-blind, Placebo-controlled Study Evaluating the Efficacy and Safety of Guselkumab in the Treatment of Subjects With Active Psoriatic Arthritis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 149
- 主要终点
- Percentage of Participants Who Achieved American College of Rheumatology (ACR) 20 Response at Week 24
研究概览
简要总结
The purpose of this study is to evaluate the efficacy, safety and tolerability of guselkumab in participants with Active Psoriatic Arthritis (PsA).
详细描述
This is a multi-center (more than one clinical site will work on a medical research study), randomized (study medication assigned to participants by chance), double-blind (neither investigator nor participant knows which treatment the participant receives), placebo-controlled (placebo is an inactive substance that is compared with a drug to test whether the drug has a real effect in a clinical trial) study to determine the efficacy and safety of guselkumab in participants with PsA. The study will consist of 4 parts: Screening period (6 weeks), a double-blind treatment period (consists of guselkumab and placebo treatment for 24 weeks), an active treatment period (guselkumab for 20 weeks), and follow-up period (12 weeks). The maximal study duration for a participant will not exceed 62 weeks including the Screening period. Eligible participants will be randomly assigned to one of two groups in a 2:1 ratio to either receive Guselkumab 100 milligram (mg) at Weeks 0, 4 then every 8 weeks or Placebo at Weeks 0, 4 then every 8 weeks until Week 24. At week 24, participants remaining in the placebo group will start to receive guselkumab 100 mg at Weeks 24, 28, 36 and 44. Participants in both treatment groups who have less than (<) 5 percent (%) improvement from baseline in both tender and swollen joint counts at Week 16 will qualify for early escape and will switch to open-label therapy with ustekinumab 45 mg or 90 mg at Weeks 16, 20, 32, and 44 based on the approved dosage for the PsA indication in the particular country of study. The efficacy will be assessed primarily by measuring percentage of participants who achieve an American College of Rheumatology (ACR) 20 Response at Week 24. Participants' safety will be monitored throughout the study.
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
- Double (Participant, Investigator)
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
- •Has had Psoriatic Arthritis (PsA) for at least 6 months before the first administration of study drug and meet classification criteria for Psoriatic Arthritis (CASPAR) at Screening
- •Had active PsA as defined by:
- •At least 3 swollen joints and at least 3 tender joints at Screening and at baseline
- •C-reactive protein (CRP) greater than or equal to (>=) 0.3 milligram (mg)/deciliter (dL) at Screening from the central laboratory
- •Has at least 1 of the PsA subsets: distal interphalangeal joint involvement, polyarticular arthritis with absence of rheumatoid nodules, arthritis mutilans, asymmetric peripheral arthritis, or spondylitis with peripheral arthritis
- •Has plaque psoriasis with body surface area (BSA) involvement greater than or equal to (>=) 3% at Screening and baseline
- •Has active PsA despite current or previous non-biologic disease-modifying antirheumatic drugs (DMARD), oral corticosteroid, and/or nonsteroidal anti-inflammatory drug (NSAID) therapy
- •If using methotrexate (MTX), oral corticosteroids or NSAIDs, the dose must be stable
排除标准
- •Have other inflammatory diseases that might confound the evaluations of benefit of guselkumab therapy, including but not limited to rheumatoid arthritis (RA), ankylosing spondylitis (AS), systemic lupus erythematosus, or Lyme disease
- •Has previously received guselkumab or ustekinumab
- •Has received more than 1 type of biologic anti-tumor necrosis factor (TNF) agent previously
- •Have received infliximab (or its biosimilars) or golimumab intraveneous (IV) within 12 weeks before the first administration of study drug
- •Have received adalimumab (or its biosimilars), golimumab subcutaneous (SC), certolizumab pegol or etanercept (or its biosimilars) within 8 weeks before the first administration of study drug
研究组 & 干预措施
Guselkumab
Participants will receive guselkumab 100 milligram (mg) subcutaneous injection (injected under the skin by way of a needle) at Weeks 0, 4, 12, 20, 28, 36, and 44, and placebo for guselkumab at Week 24 to maintain the blind. Participants who enter early escape at Week 16 will switch to open label therapy with ustekinumab 45 mg or 90 mg at Weeks 16, 20, 32, and 44 based on the approved dosage in the particular country of the study.
干预措施: Guselkumab (Drug)
Guselkumab
Participants will receive guselkumab 100 milligram (mg) subcutaneous injection (injected under the skin by way of a needle) at Weeks 0, 4, 12, 20, 28, 36, and 44, and placebo for guselkumab at Week 24 to maintain the blind. Participants who enter early escape at Week 16 will switch to open label therapy with ustekinumab 45 mg or 90 mg at Weeks 16, 20, 32, and 44 based on the approved dosage in the particular country of the study.
干预措施: Ustekinumab (Drug)
Guselkumab
Participants will receive guselkumab 100 milligram (mg) subcutaneous injection (injected under the skin by way of a needle) at Weeks 0, 4, 12, 20, 28, 36, and 44, and placebo for guselkumab at Week 24 to maintain the blind. Participants who enter early escape at Week 16 will switch to open label therapy with ustekinumab 45 mg or 90 mg at Weeks 16, 20, 32, and 44 based on the approved dosage in the particular country of the study.
干预措施: Placebo (Drug)
Placebo
Participants will receive placebo for guselkumab at Weeks 0, 4, 12, and 20, and guselkumab 100 mg subcutaneous injection at Weeks 24, 28, 36, and 44. Participants who enter early escape at Week 16 will switch to open label therapy with ustekinumab 45 mg or 90 mg at Weeks 16, 20, 32, and 44 based on the approved dosage in the particular country of the study.
干预措施: Guselkumab (Drug)
Placebo
Participants will receive placebo for guselkumab at Weeks 0, 4, 12, and 20, and guselkumab 100 mg subcutaneous injection at Weeks 24, 28, 36, and 44. Participants who enter early escape at Week 16 will switch to open label therapy with ustekinumab 45 mg or 90 mg at Weeks 16, 20, 32, and 44 based on the approved dosage in the particular country of the study.
干预措施: Ustekinumab (Drug)
Placebo
Participants will receive placebo for guselkumab at Weeks 0, 4, 12, and 20, and guselkumab 100 mg subcutaneous injection at Weeks 24, 28, 36, and 44. Participants who enter early escape at Week 16 will switch to open label therapy with ustekinumab 45 mg or 90 mg at Weeks 16, 20, 32, and 44 based on the approved dosage in the particular country of the study.
干预措施: Placebo (Drug)
结局指标
主要结局
Percentage of Participants Who Achieved American College of Rheumatology (ACR) 20 Response at Week 24
时间窗: Week 24
ACR 20 response: at least 20% improvement from baseline in both swollen joint (66 joints) and tender joint (68 joints) counts and at least 20% improvement from baseline in 3 of following 5 assessments: patient's assessment of pain (VAS: 0-100 millimeter \[mm\], 0=no pain and 100=worst possible pain), patient's global assessment of disease activity on arthritis (VAS:0-100mm, 0=excellent and 100=poor), physician's global assessment of disease activity (VAS:0-100mm; 0=no arthritis activity and 100 = extremely active arthritis), patient's assessment of physical function measured by HAQ-DI (defined as a 20-question instrument assessing 8 functional areas;derived HAQ-DI ranges from 0=no difficulty, to 3=inability to perform a task in that area) and serum CRP. Treatment Failure (TF) criteria: Discontinued study drug due to lack of efficacy or worsening of PsA, initiated or increased dose of methotrexate or oral corticosteroids, or initiated prohibited PsA treatments. FAS is full analysis set.
次要结局
- Percentage of Participants Who Achieved a Psoriasis Area and Severity Index (PASI)-75 Response at Week 24(Week 24)
- Percentage of Participants Who Achieved an ACR 20 Response at Week 16(Week 16)
- Percentage of Participants Who an Achieved ACR 50 Response at Week 24(Week 24)
- Percent Change From Baseline in Leeds Enthesitis Index (LEI) Scores Among Participants With Enthesitis at Week 24(Baseline and Week 24)
- Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 24(Baseline and Week 24)
- Percentage of Participants Who Achieved ACR 20, ACR 50, and ACR 70 Responses at Weeks 4, 8, 12, 16, 20, and 24(Weeks 4, 8, 12, 16, 20, and 24)
- Change From Baseline in HAQ-DI Score at Weeks 24, 28, 32, 36, 44, and 56(Baseline and Weeks 24, 28, 32, 36, 44, 56)
- Percentage of Participants Who Achieved a HAQ-DI Response With Greater Than or Equal to (>=) 0.3 Improvement From Baseline in HAQ-DI Score at Weeks 4, 8, 12, 16, 20, and 24(Weeks 4, 8, 12, 16, 20, and 24)
- Percentage of Participants Who Achieved an HAQ-DI Response With >= -0.3 Improvement From Baseline in HAQ-DI Score at Weeks 24, 28, 32, 36, 44, and 56(Weeks 24, 28, 32, 36, 44, 56)
- Percentage of Participants With Dactylitis at Weeks 4, 8, 16, and 24(Weeks 4, 8, 16, and 24)
- Percent Change From Baseline in LEI Scores at Week 4, 8, 16, and 24(Baseline and Weeks 4, 8, 16, 24)
- Percent Change From Baseline in LEI Scores at Weeks 24, 28, 32, 44, and 56(Baseline and Weeks 24, 28, 32, 44, 56)
- Percent Change From Baseline in Dactylitis Scores Among Participants With Dactylitis at Baseline at Week 24(Baseline and Week 24)
- Percent Change From Baseline in the ACR Components at Weeks 24, 28, 32, 36, 44 and 56(Basline and Weeks 24, 28, 32, 36, 44, 56)
- Percentage of Participants Who Achieved ACR 20, ACR 50, and ACR 70 Responses at Weeks 24, 28, 32, 36, 44, and 56(Weeks 24, 28, 32, 36, 44, and 56)
- Percent Change From Baseline in the ACR Components at Weeks 12 and 24(Baseline and Weeks 12, 24)
- Percent Change From Baseline in Dactylitis Scores at Weeks 4, 8, 16, and 24(Baseline and Weeks 4, 8, 16, 24)
- Percentage of Participants With Dactylitis at Weeks 24, 28, 32, 44, and 56(Weeks 24, 28, 32, 44, and 56)
- Percentage of Participants With Enthesitis Based on LEI Score at Weeks 4, 8, 16, and 24 in Participants With Enthesitis at Baseline(Weeks 4, 8, 16, and 24)
- Change From Baseline in PASDAS Score at Weeks 24 and 44(Baseline and Weeks 24, 44)
- Change From Baseline in HAQ-DI Response at Weeks 4, 8, 12, 16, 20, and 24(Baseline and Weeks 4, 8, 12, 16, 20, 24)
- Change From Baseline in Psoriatic ArthritiS Disease Activity Score (PASDAS) Score at Weeks 16 and 24(Baseline and Weeks 16, 24)
- Change From Baseline in Modified Composite Psoriatic Disease Activity Index (mCPDAI) Score at Weeks 16 and 24(Baseline and Weeks 16, 24)
- Change From Baseline in Disease Activity Index for Psoriatic Arthritis (DAPSA) Score at Weeks 4, 8, 12, 16, 20 and 24(Baseline and Weeks 4, 8, 12, 16, 20, 24)
- Percentage of Participants Who Achieved MDA at Weeks 24 and 44(Weeks 24 and 44)
- Change From Baseline in RAPID3 Score at Weeks 24 and 44(Baseline and Weeks 24, 44)
- Percent Change From Baseline in Dactylitis Scores at Weeks 24, 28, 32, 44, 56(Baseline and Weeks 24, 28, 32, 44, 56)
- Change From Baseline in GRAppa Composite scorE (GRACE) Index Score at Weeks 16 and 24(Baseline and Weeks 16, 24)
- Change From Baseline in GRACE Index Score at Weeks 24 and 44(Baseline and Weeks 24, 44)
- Change From Baseline in mCPDAI Index Score at Weeks 24 and 44(Baseline and Weeks 24, 44)
- Change From Baseline in DAPSA Index Score at Weeks 24, 28, 32, 36, 44, and 56(Baseline and Weeks 24, 28, 32, 36, 44, 56)
- Percentage of Participants Who Achieved Minimal Disease Activity (MDA) at Weeks 16 and 24(Weeks 16 and 24)
- Change From Baseline in the MCS Scores of SF-36 at Weeks 24 and 44(Baseline and Weeks 24, 44)
- Change From Baseline in Norm-based SF-36 Scale at Week 24 and 44(Baseline and Weeks 24, 44)
- Percentage of Participants With Enthesitis Based on LEI at Weeks 24, 28, 32, 44, and 56 in Participants With Enthesitis at Baseline(Weeks 24, 28, 32, 44, and 56)
- Change From Baseline in Norm-based SF-36 Scales at Week 16 and 24(Baseline and Weeks 16, 24)
- Change From Baseline in the Physical and Mental Component Summary (PCS and MCS) Scores of 36- Item Short Form Health Assessment Questionnaire (SF-36) at Weeks 16 and 24(Baseline and Weeks 16, 24)
- Change From Baseline in the PCS Scores of SF-36 at Weeks 24 and 44(Baseline and Weeks 24, 44)
- Change From Baseline in Routine Assessment of Patient Index Data 3 (RAPID3) Score at Weeks 16 and 24(Baseline and Weeks 16, 24)
- Percent Change From Baseline in PASI Score at Weeks 24, 28, 32, 44, and 56(Baseline and Weeks 24, 28, 32, 44, 56)
- Percentage of Participants Who Achieved a PASI 50, PASI 75, PASI 90 and PASI 100 Response at Weeks 16 and 24(Weeks 16 and 24)
- Percentage of Participants Who Achieved a PASI 50, PASI 75, PASI 90 and PASI 100 Response at Weeks 24, 28, 32, 44, and 56(Weeks 24, 28, 32, 44, and 56)
- Percent Change From Baseline in PASI Score at Weeks 4, 8, 16, and 24(Baseline and Weeks 4, 8, 16, 24)