A Phase 3b, Randomized, Double-blind, Parallel Group, Multicenter Study to Evaluate Further Therapeutic Strategies With Guselkumab in Patients With Moderate-to-Severe Plaque-Type Psoriasis
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 880
- 试验地点
- 90
- 主要终点
- Group 2a and Group 2b: Percentage of Participants Who Achieved an Absolute Psoriasis Area and Severity Index (PASI) Score Less Than (<) 3 at Week 68
研究概览
简要总结
The purpose of this study is to demonstrate that Super-Responders (SRe; defined as psoriasis participants who receive on-label guselkumab treatment until week 20 and respond with a Psoriasis Area and Severity Index score (PASI) = 0 at weeks 20 and 28) maintain control of disease until week 68 with prolonged treatment intervals of 16 weeks (guselkumab 100 mg every 16 weeks).
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
- Triple (Participant, Care Provider, 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 a disease duration of plaque psoriasis of either less than or equal to (<=2) years or (greater than (>2) years calculated from date at which first symptoms [plaque] were reported by subject to date of screening visit at screening; approximately 40 percentage (%) of participants must have a disease duration <=2 years
- •Has moderate-to-severe plaque-psoriasis defined by a Psoriasis Area and Severity Index (PASI) score >10 or affected body surface area (BSA) >10%) and additionally a Dermatology Life Quality Index (DLQI) score >10 at baseline (week 0)
- •Have no signs or symptoms suggestive of active tuberculosis (TB) upon medical history and/or physical examination
- •Agrees not to receive a live virus or live bacterial vaccination during the study, or within 3 months after the last administration of study drug
- •Agrees not to receive a Bacille Calmette-Guerin (BCG) vaccination during the study, or within 12 months after the last administration of study drug
排除标准
- •Has previously received any therapeutic agent directly targeted to interleukin (IL) -23 (including but not limited to guselkumab, tildrakizumab [MK3222], risankizumab [BI-655066])
- •Has received any systemic immunosuppressant (for example, methotrexate, azathioprine, cyclosporine, 6-thioguanine, mercaptopurine, mycophenolate mofetil, tacrolimus, fumaric acid esters), or anakinra within 4 weeks of the first administration of study drug.
- •Tests positive for hepatitis B virus (HBV) infection or who are seropositive for antibodies to hepatitis C virus (HCV), unless they have 2 negative HCV RNA test results 6 months apart after completing antiviral treatment and prior to baseline and have a third negative HCV RNA test result at baseline
- •Has received natalizumab, belimumab, or agents that modulate B cells or T cells (e.g., rituximab, alemtuzumab, abatacept, or visilizumab) within 12 months of the first administration of study drug
- •Has received any anti - tumor necrosis factor (TNF)-α biologic therapy within 3 months before the first administration of study drug
研究组 & 干预措施
Part 2: Guselkumab q8w
Participants (Non SRe) in group 2c with a PASI score greater than (>) 0 at week 20 and/or 28 will continue to receive guselkumab 100 mg q8w until week 60.
干预措施: Guselkumab (Drug)
Part 1: Guselkumab
Participants in group 1 (Part 1) will receive 100 milligram (mg) guselkumab subcutaneously (SC) at Weeks 0, 4, 12 and 20.
干预措施: Guselkumab (Drug)
Part 2: Guselkumab q8w and Guselkumab q16w
Eligible participants from Part 1 will continue to participate in Part 2. Participants (super responder [SRe]) with a Psoriasis Area and Severity Index (PASI) score = 0 at weeks 20 and 28 will be randomized to guselkumab 100 mg every 8 weeks (q8w) (group 2a) or guselkumab 100 mg q16w (group 2b), at weeks 28 to 60. Group 2b will receive placebo injection at weeks 28, 44 and 60 to keep the comparison double blind. Participants losing control of disease (PASI score >5) during study Part 2 (until week 60), will enter the re-treatment arm (group 2d) and receive guselkumab 100mg q8w (at re-treatment week 0), followed by administration at re-treatment-weeks 8 and 16.
干预措施: Guselkumab (Drug)
Part 2: Guselkumab q8w
Participants (Non SRe) in group 2c with a PASI score greater than (>) 0 at week 20 and/or 28 will continue to receive guselkumab 100 mg q8w until week 60.
干预措施: Placebo Injection (Drug)
Part 3: Guselkumab Withdrawal
Participants from groups 2a and 2b with a PASI score <3 at week 68 will be included in Part 3 (group 3a and 3b) and be withdrawn from guselkumab. Study visits will be conducted every 12 weeks until week 220 (follow-up). Participants with fluctuating disease (PASI score greater than or equal to [>=] 3) at week 68 or PASI >5 (participants losing control of disease) at any visit during part 3 after week 68 will get an opportunity to enter the re-treatment-arm (group 3c) in which participants will receive three guselkumab injections of 100 mg q8w.
干预措施: Guselkumab (Drug)
结局指标
主要结局
Group 2a and Group 2b: Percentage of Participants Who Achieved an Absolute Psoriasis Area and Severity Index (PASI) Score Less Than (<) 3 at Week 68
时间窗: Week 68
Percentage of participants who achieved an absolute PASI \<3 at Week 68 were reported. The PASI is a system used for assessing and grading the severity of psoriatic lesions and their response to therapy. In the PASI system, the body is divided into 4 regions: the head, trunk, upper extremities, and lower extremities. Each of these areas is assessed separately for the percentage of the body surface area involved, which translates to a numeric score that ranged from 0 (indicated no involvement) to 6 (90 percent \[%\]-100% involvement), and for erythema, induration and scaling, which are each rated on a scale of 0 to 4. The PASI produces a numeric score that could range from 0 (no psoriasis) to 72 (maximum psoriasis). Higher score indicated greater severity of psoriasis.
次要结局
- Group 1: Percentage of Participants With an Absolute PASI Score = 0 at Weeks 12, 16, 20 and 28(Weeks 12, 16, 20 and 28)
- Groups 1 and 2c: Time to Improvement From Baseline (Week 0) in PASI Score(Group 1: Week 0 up to Week 28; Group 2c: Week 28 up to Week 68)
- Groups 1, 2a, 2b, 2c, 3a and 3b: Percentage of Participants With Short (<=2 Years) and Longer (>2 Years) Disease Duration Who Achieved an Absolute PASI Score of 0, <=1 and <3 at Weeks 20, 28, 68, 116, 164 and 220(Group 1: Weeks 20 and 28; Groups 2a, 2b, 2c: Week 68; Groups 3a and 3b: Weeks 116, 164 and 220)
- Group 3a and Group 3b: Percentage of Participants With Short (<=2 Years) and Longer (>2 Years) Disease Duration Who Retain Disease Control (Absolute PASI Score < 3)(From Week 68 up to Week 220)
- Groups 1, 2a, 2b, 2c, 3a and 3b: Percentage of Participants Who Achieved a PASI 75/90/100 Response at Weeks 20, 28, 68, 116, 164, and 220(Group 1: Weeks 20, 28; Groups 2a, 2b, 2c: Week 68; Groups 3a, 3b: Weeks 116, 164 and 220)
- Group 3a and Group 3b: Time to Loss of Disease Control (Absolute PASI Score >5) After Treatment Withdrawal(From Week 68 up to Week 220)
- Groups 1, 2a, 2b, 2c, 3a, 3b and 3c: Change From Baseline (Week 0) in Dermatology Life Quality Index (DLQI) Score(Group 1: Baseline (Week 0), Week 28; Group 2a, 2b, 2c: Baseline (Week 0), Week 68; Group 3a and Group 3b:Baseline (Week 0), Week 116, 164 and 220; Group 3c: Baseline (Re-Treatment [R] Week 0), Week R24)
- Groups 1, 2a, 2b, 2c, 3a, 3b and 3c: Percentage of Participants Who Achieved a DLQI Score 0/1 and <5(Group 1: Week 28; Groups 2a, 2b, 2c: Week 68; Groups 3a and 3b: Week 116, 164 and 220; Group 3c: Week R24)
- Groups 1, 2a, 2b, 2c, 3a, and 3b: Percent Change From Baseline (Week 0) in Psoriasis- Affected Body Surface Area (BSA)(Group 1: Baseline (Week 0), Week 12, 28; Group 2a, 2b, 2c: Baseline (Week 0), Week 52 and 68, Group 3a, 3b: Baseline (Week 0), Week 80, 104, 116, 140, 164, 188, 212 and 220)
- Groups 1, 2a, 2b, 2c, 3a and 3b: Change From Baseline in Nail Assessment in Psoriasis and Psoriatic Arthritis- Clinical (NAPPA-CLIN) at Weeks 28, 68, 116, 164 and 220(Group 1: Baseline (Week 0), Week 28; Group 2a, 2b, 2c: Baseline (Week 0), Week 68; Group 3a and Group 3b: Baseline (Week 0), Week 116, 164, and 220)
- Groups 1, 2a, 2b, 2c, 3a and 3b: Change From Baseline (Week 0) in the Signs and Symptoms Aggregate Scores of the Psoriasis Symptoms and Signs Diary (PSSD) at Weeks 28, 68, 116, 164 and 220(Group 1: Baseline (Week 0), Week 28; Group 2a, 2b, 2c: Baseline (Week 0), Week 68; Group 3a and Group 3b: Baseline (Week 0), Week 116, 164, and 220)
- Groups 2a, 2b and 2c: Percentage of Participants Who Achieved a PSSD Sign Score = 0 at Week 68 in Participants With a PSSD Sign Score >= 1 at Week 28(Week 68)
- Groups 2a and 2b: Serum Trough Guselkumab Levels at Weeks 20, 28, 36 and 68(At Weeks 20, 28, 36, 68)
- Groups 2d and 3c: Percentage of Participants Who Were Re-Treated Due to Loss of Disease Control (PASI >5) and Regain Control of Disease (PASI <3) 24 Weeks After Start of Re-Treatment(Week R0 up to Week R24)
- Groups 1, 2a, 2b, 2c, 2d,3a, 3b, and 3c: Percentage of Participants With Adverse Events as a Measure of Safety and Tolerability(Group 1: From Week 0 to Week 28; Group 2a,2b 2c: From Week 28 to Week 68; Group 3a, 3b: From Week 68 to Week 220; Group 2d, 3c: From Week R0 to Week R28)
- Groups 1, 2a, 2b, 2c, 2d, 3a,3b and 3c: Number of Participants With Clinically Significant Laboratory Abnormalities(Group 1: Week 20, Group 2a, 2b,2c: Week 68 and Group 2d and 3c: Week R28)