A Phase 3, Randomized, Placebo-controlled, Parallel-group, Multicenter Study to Evaluate the Efficacy and Safety of Guselkumab in Participants With Fistulizing, Perianal Crohn's Disease
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 288
- 试验地点
- 155
- 主要终点
- Percentage of Participants who Achieve Combined Fistula Remission at Week 24
研究概览
简要总结
The purpose of this study to evaluate the clinical efficacy of guselkumab in fistulizing, perianal Crohn's disease and to assess the overall safety of guselkumab.
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
- •Must have a diagnosis of Crohn's disease with a minimum duration of at least 3 months
- •Has at least one active draining perianal fistula as a complication of Crohn's disease, confirmed by screening magnetic resonance imaging (MRI) results
- •Has previously demonstrated lack of initial response (that is primary non-responders), responded initially but then lost response with continued therapy (that is secondary non-responders), or were intolerant to a maximum of 2 classes of advanced drug therapies at a dose approved for the treatment of Crohn's disease (that is infliximab, adalimumab, certolizumab pegol, vedolizumab, or approved biosimilars for these agents) or JAK inhibitors licensed for Crohn's disease treatment (that is, upadacitinib)
排除标准
- •Has a very severe luminal disease activity
- •History of concurrent rectovaginal fistulas (other types of concurrent fistula should be confirmed with the sponsor), rectal and/or anal stenosis, stoma or functioning ostomy (include all current stoma types abscess or collections which are not properly drained) colonic mucosal dysplasia or pre-cancerous lesions that have not been removed, demyelinating disease, or systemic lupus erythematosus
- •Has complications of CD, such as symptomatic strictures or stenoses, short gut syndrome, or any other manifestation that might be anticipated to require surgery or preclude fistula evaluation
- •Any medical contraindications preventing study participation
- •Has a history of ongoing, chronic or recurrent enteral or systemic infectious disease
研究组 & 干预措施
Group 1: Guselkumab
Participants will receive guselkumab Dose 1 intravenous (IV) infusion followed by Dose 2 subcutaneously (SC). Participants will receive matching placebo to maintain the blind. Participants who are eligible and willing to continue guselkumab may enter the Long-Term Extension (LTE) period and continue to receive guselkumab.
干预措施: Guselkumab (Drug)
Group 2: Guselkumab
Participants will receive guselkumab Dose 1 IV infusion followed by Dose 3 SC. Participants will receive matching placebo to maintain the blind. At Week 24, guselkumab Dose 3 SC non-responders will switch to receive guselkumab dose 2 SC. Participants who are eligible and willing to continue guselkumab may enter the LTE period and continue to receive guselkumab.
干预措施: Guselkumab (Drug)
Group 3: Placebo
Participants will receive placebo IV infusion followed by placebo SC. At Week 24, placebo non-responders will continue to receive guselkumab Dose 4 followed by guselkumab Dose 2 SC. Participants will receive matching placebo to maintain the blind. Participants who are eligible and willing to continue guselkumab may enter the LTE period and continue to receive guselkumab.
干预措施: Guselkumab (Drug)
Group 1: Guselkumab
Participants will receive guselkumab Dose 1 intravenous (IV) infusion followed by Dose 2 subcutaneously (SC). Participants will receive matching placebo to maintain the blind. Participants who are eligible and willing to continue guselkumab may enter the Long-Term Extension (LTE) period and continue to receive guselkumab.
干预措施: Placebo (Drug)
Group 2: Guselkumab
Participants will receive guselkumab Dose 1 IV infusion followed by Dose 3 SC. Participants will receive matching placebo to maintain the blind. At Week 24, guselkumab Dose 3 SC non-responders will switch to receive guselkumab dose 2 SC. Participants who are eligible and willing to continue guselkumab may enter the LTE period and continue to receive guselkumab.
干预措施: Placebo (Drug)
Group 3: Placebo
Participants will receive placebo IV infusion followed by placebo SC. At Week 24, placebo non-responders will continue to receive guselkumab Dose 4 followed by guselkumab Dose 2 SC. Participants will receive matching placebo to maintain the blind. Participants who are eligible and willing to continue guselkumab may enter the LTE period and continue to receive guselkumab.
干预措施: Placebo (Drug)
结局指标
主要结局
Percentage of Participants who Achieve Combined Fistula Remission at Week 24
时间窗: Week 24
Percentage of participants who achieve combined fistula remission at Week 24 will be reported. Combined fistula remission is defined as 100 percentage (%) closure of all treated external openings without development of new fistulas or abscesses and without any drainage by the external openings \[occurring spontaneously or after gentle finger compression\] and absence of collections greater than (\>) 2 centimeters (cm) of the perianal fistulas in at least two of three dimensions, confirmed by a blinded central review of the magnetic resonance imaging \[MRI\] results.
次要结局
- Percentage of Participants who Achieve Combined Fistula Remission at Week 48(Week 48)
- Percentage of Participants who Achieve Clinically Assessed Fistula Remission(Week 24)
- Percentage of Participants who Achieve Radiological Fistula Remission Based on Radiological Findings Assessed by MRI(Week 24)
- Percentage of Participants who Achieve Clinically Assessed Fistula Response at Week 24(Week 24)
- Percentage of Participants who Achieve Clinically Assessed Fistula Response at Week 12(Week 12)
- Change from Baseline in Crohn's Disease Activity Index (CDAI) by Visit Over Time Through Week 48(Baseline up to Week 48)
- Percentage of Participants who Achieve Clinical Remission (CDAI less than [<] 150) by Visit Over Time Through Week 48 Among Participants with CDAI Greater than (>) 150 at Baseline(Through Week 48)
- Percentage of Participants who Achieve a Clinical Response by Visit Over Time Through Week 48 Among Participants with CDAI >150 at Baseline(Through Week 48)
- Percentage of Participants who Achieve Steroid-free Clinical Remission by Visit Over Time Through Week 48 Among Participants with CDAI >150 at Baseline(Through Week 48)
- Percentage of Participants who Achieve Combined Clinical Remission and Clinically Assessed Fistula Remission Among Participants with CDAI >220 at Baseline(Week 24 and Week 48)
- Percentage of Participants who Achieve Combined Clinical Response and Clinically Assessed Fistula Remission Among Participants with CDAI >220 at Baseline(Week 24 and Week 48)
- Percentage of Participants who Achieve Combined Clinical Response and Clinically Assessed Fistula Response Among Participants With CDAI >220 at Baseline(Week 24 and Week 48)
- Percentage of Participants who Achieve Combined Clinical Remission and Clinically Assessed Fistula Response among Participants with CDAI >220 at Baseline(Week 24 and Week 48)
- Percentage of Participants who Achieve Combined Clinical Response and Clinically Assessed Fistula Response at Week 24 and Week 48(Week 24 and Week 48)
- Percentage of Participants who Achieve Combined Clinical Response and Clinically Assessed Fistula Remission at Week 24 and Week 48(Week 24 and Week 48)
- Percentage of Participants who Achieve Combined Clinical Remission and Clinically Assessed Fistula Response at Week 24 and Week 48(Week 24 and Week 48)
- Percentage of Participants who Achieve Combined Clinical Remission and Clinically Assessed Fistula Remission at Week 24 and Week 48(Week 24 and Week 48)
- Change from Baseline in Perianal Disease Activity Index (PDAI) Overall Score, Discharge Score, and Pain Score by Visit Over Time Through Week 48(Baseline up to Week 48)
- Percentage of Participants who Achieve Clinically Assessed Fistula Response by Visit Over Time Through Week 48(Through Week 48)
- Percentage of Participants who Achieve Clinically Assessed Fistula Remission by Visit over Time Through Week 48(Through Week 48)
- Percentage of Participants who Achieve Clinically Assessed Fistula Remission at Week 48 Among the Participants who Achieve Clinical Fistula Remission at Week 24(Week 48)
- Percentage of Participants who Achieve Clinically Assessed Fistula Remission at Week 48 Among Those who Achieve Fistula Remission or Response at Week 24(Week 48)
- Time to Clinical Fistula Remission(Up to Week 96)
- Percentage of Participants who Achieve Radiological Fistula Predominantly Fibrotic Status for all Existent Fistulas Assessed by MRI at Week 24 and Week 48(Week 24 and Week 48)
- Percentage of participants who Achieve Radiological Remission Based on Radiological Findings Assessed by MRI at Week 48(Week 48)
- Percentage of Participants who Achieve Radiological Remission Assessed by MRI at Week 48 Among the Participants who Achieve Radiological Remission at Week 24(Week 48)
- Percentage of Participants who Achieve Combined Clinically Assessed and Radiological Fistula Remission at Week 48 Among the Participants who Achieve Combined Clinical and Radiological Fistula Remission at Week 24(Week 48)
- Percentage of Participants who Achieve Combined Clinically Assessed and Radiological Fistula Remission at Week 48 Among the Participants with Clinical Fistula Response at Week 24(Week 48)
- Percentage of Participants with Proctitis at Week 48 Among Participants with MRI-confirmed Proctitis at Baseline(Week 48)
- Change from Baseline in Magnetic Resonance Novel Index for Fistula imaging in Crohn's disease (MAGNIFI-CD) by Visit Over Time Through Week 48(Baseline up to Week 48)
- Change from Baseline in the Jorge-Wexner Score by Visit Over Time Through Week 48(Baseline; Through Week 48)
- Change from Baseline in the Inflammatory Bowel Disease-Disability Index (IBD-DI) by Visit Over Time Through Week 48(Baseline; Through Week 48)
- Change from Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) by Visit Over Time Through Week 48(Baseline up to Week 48)
- Change From Baseline in Functional Assessment of Chronic Illness Therapy-fatigue (FACIT-F) Score by Visit Over Time Through Week 48(Baseline; Up to Week 48)
- Change From Baseline in Work Productivity and Activity Impairment Questionnaire: Crohn's Disease (WPAI:CD) by Visit Over Time Through Week 48(Baseline; Up to Week 48)
- Number of Participants with Treatment-emergent Serious Adverse Events (TESAEs)(Up to Week 48 and Week 96)
- Change from Baseline in Quality-of-life as Assessed by European Quality-of-Life Five Dimension Five Level Scale (EQ5D-5L) Score by Visit Over Time Through Week 48(Baseline up to Week 48)
- Number of Participants with Treatment-emergent Adverse Events (TEAEs)(Up to Week 48 and Week 96)