NCT06408935进行中（未招募）3 期
A Phase 3b, Open-label, Multicenter Study to Evaluate Transmural Healing and Disease Modifying Effect of Guselkumab in Crohn's Disease Patients
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 120
- 试验地点
- 141
- 主要终点
- Percentage of Participants Achieving a Magnetic Resonance Index of Activity (MaRIA) Less Than (<)11 in All Intestinal Segments at Week 48
研究概览
简要总结
The purpose of this study is to evaluate the efficacy of guselkumab in healing of all layers of the digestive tract (transmural healing) with the help of a score called Magnetic Resonance Index of Activity (MaRIA) based on a scan at Week 48.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
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 luminal Crohn's disease (CD) of at least 3 months duration (defined as a minimum of 12 weeks), with colitis, ileitis, or ileocolitis, confirmed at any time in the past by radiography, histology, and/or endoscopy
- •Has clinically active CD, defined as a baseline CD activity index (CDAI) score greater than or equal to (>=)220 but <=450 and either: a. Mean daily stool frequency (SF) count >=4, based on the unweighted CDAI component of the number of liquid or very soft stools or b. Mean daily AP score >=2, based on the unweighted CDAI component of abdominal pain (AP)
- •Active transmural activity in at least one segment (segmental magnetic resonance index of activity [MaRIA] >= 11)
- •a. Has demonstrated inadequate response/intolerance to conventional therapy; b. 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 was intolerant to a maximum of 1 class of advanced therapies at a dose approved for the treatment of Crohn's disease (that is, janus kinase [JAK] inhibitors, infliximab, adalimumab, certolizumab pegol, vedolizumab, ustekinumab, or approved biosimilars for these agents)
排除标准
- •Has complications of Crohn's disease, such as symptomatic strictures or stenoses (unless less than [<]3 centimeter (cm) dilatation and not symptomatic or displaying associated fistula/fistulae and/or or abscess), fibrotic stenosis, internal fistulas, short gut syndrome, or any other manifestation, that might be anticipated to require surgery, could preclude the use of the CDAI to assess response to therapy, or would possibly confound the ability to assess the effect of treatment with guselkumab
- •Currently has or is suspected to have an abscess. Recent cutaneous and perianal abscesses are not exclusionary if drained and adequately treated at least 3 weeks before baseline, or 8 weeks before baseline for intra-abdominal abscesses, provided that there is no anticipated need for any further surgery. Participants with active perianal fistulas may be included if there are no associated stenoses, no anticipated surgery and no abscesses currently identified
- •Has had any kind of bowel resection within 6 months, or any other intra-abdominal or other major surgery within 12 weeks before baseline
- •Has a draining (that is, functioning) stoma or ostomy
- •Has a stool culture or other examination positive for an enteric pathogen, including Clostridioides difficile (formerly known as Clostridium difficile) toxin, in the previous 4 months, unless a repeat examination is negative and there are no signs of ongoing infection with that pathogen
研究组 & 干预措施
Guselkumab
Experimental
Participants will receive guselkumab 200 milligram (mg) intravenously (IV) at week 0, 4 and 8. Afterwards, participants will be alternately assigned at study level to 2 dose cohorts, high dose (200 mg subcutaneous (SC) every 4 weeks (Q4W) starting at week 12) through week 92 or low dose (100 mg SC every 8 weeks (Q8W) starting at week 16) through week 88. Starting at Week 24, participants in the low-dose cohort will be permitted to escalate to the 200 mg SC Q4W regimen if they are symptomatic and at the discretion of the investigator.
干预措施: Guselkumab (Drug)
结局指标
主要结局
Percentage of Participants Achieving a Magnetic Resonance Index of Activity (MaRIA) Less Than (<)11 in All Intestinal Segments at Week 48
时间窗: At Week 48
Percentage of participants achieving a MaRIA \<11 in all intestinal segments at Week 48 will be reported. The MaRIA scoring system is used to grade severity in Crohn's Disease (CD) by assessing ileocolonic CD activity on contrast-enhanced magnetic resonance imaging (MRI) enterography. Active disease is defined as a MaRIA score greater than or equal to (\>=)7 whereas severe disease is defined as a MaRIA score \>=11.
次要结局
- Percentage of Participants Achieving a MaRIA <11 in All Intestinal Segments at Weeks 16 and 96.(At Weeks 16 and 96)
- Percentage of Participants Achieving a MaRIA <11 and a Reduction of >=5 Points From Baseline in All Segments at Weeks 16, 48, and 96(At Weeks 16, 48, and 96)
- Percentage of Participants Achieving a MaRIA <11 in All Segments and Endoscopic Remission at Weeks 48 and 96(At Week 48 and 96)
- Percentage of Participants Achieving a MaRIA <11 in All Segments and Endoscopic Response at Weeks 48 and 96.(At Weeks 48 and 96)
- Percentage of Participants Achieving a MaRIA <11 in All Segments and Biomarkers Remission(At Weeks 16, 48 and 96)
- Percentage of Participants Achieving Endoscopic Response at Weeks 48 and 96(Weeks 48 and 96)
- Percentage of Participants Achieving Endoscopic Remission at Weeks 48 and 96(At Weeks 48 and 96)
- Absolute Value of SES-CD Total Score Through Week 96(Baseline up to Week 96)
- Change From Baseline in the SES-CD Total Score Through Week 96(Up to Week 96)
- Percentage of Participants (Not Receiving Corticosteroids) Achieving Endoscopic Remission at Weeks 48 and 96(Baseline, at Weeks 48 and 96)
- Percentage of Participants Achieving a MaRIA <11 in All Segments, Patient-Reported Outcome-2 (PRO-2) Remission, and No Worsening of Abdominal Pain (AP) or Stool Frequency (SF) From Baseline(At Weeks 16, 48 and 96)
- Percentage of Participants Achieving a MaRIA <11 in All Segments, PRO-2, and Endoscopic Remission(At Weeks 48 and 96)
- Absolute Value of Global Simple MaRIA Score Through Week 96(Baseline up to Week 96)
- Change From Baseline in the Global Simple MaRIA Score Through Week 96(Up to Week 96)
- Percentage of Participants Achieving a MaRIA <7 in All Intestinal Segments and Not Receiving Corticosteroids at Weeks 16, 48, and 96(At Weeks 16, 48, and 96)
- Percentage of Participants Achieving Transmural Segmental Response with Intestinal Ultrasound (IUS) at Weeks 4, 8, 16, 48, and 96(Baseline, at Weeks 4, 8, 16, 48, and 96)
- Percentage of Participants with Transmural Response (total) at Weeks 4, 8, 16, 48, and Week 96(Baseline, at Weeks 4, 8, 16, 48, and Week 96)
- Percentage of Participants Achieving a MaRIA <7 in All Intestinal Segments at Weeks 16, 48 and 96(At Weeks 16, 48 and 96)
- Percentage of Participants Achieving a MaRIA <7 in All Segments and Endoscopic Remission at Weeks 48 and 96(At Weeks 48 and 96)
- Percentage of Participants Achieving Transmural Remission with IUS at Weeks 4, 8, 16, 48, and 96(At Weeks 4, 8, 16, 48, and 96)
- Absolute Value of International Bowel Ultrasound Segmental Activity Score (IBUS-SAS) Through Week 96(Baseline up to Week 96)
- Change from Baseline in International Bowel Ultrasound Segmental Activity Score (IBUS-SAS) Through Week 96(Up to Week 96)
- Percentage of Participants Achieving IBUS-SAS Response at Weeks 4, 8, 16, 48, and Week 96(Baseline, at Weeks 4, 8, 16, 48, and Week 96)
- Percentage of Participants Achieving BWT <=3 mm for Ileum and Colon Plus CDS 0, in all segments and Participants Not Receiving Corticosteroids at Weeks 4, 8, 16, 48, and 96(At Weeks 4, 8, 16, 48, and 96)
- Absolute Value of BWT through Week 96(Baseline up to Week 96)
- Change From Baseline in BWT Through Week 96(Up to Week 96)
- Absolute Value of Simple IUS Score For CD (SUS-CD) Score Through Week 96(Baseline up to Week 96)
- Change From Baseline in the SUS-CD Score Through Week 96(Up to Week 96)
- Percentage of Participants Achieving Endoscopic Healing of the Intestinal Mucosa at Weeks 48 and 96(At Weeks 48 and 96)
- Percentage of Participants Achieving Crohn's Disease Activity Index (CDAI) <150 at Weeks 4, 8, 16, 48 and 96(At Weeks 4, 8, 16, 48 and 96)
- Percentage of Participants Achieving a Reduction in the CDAI Score of >=100 points or CDAI <150 From Baseline at Weeks 4, 8, 16, 48, and 96(At Weeks 4, 8, 16, 48, and 96)
- Percentage of Participants (Not Receiving Corticosteroids) Achieving CDAI Score <150 at Weeks 4, 8, 16, 48 and 96(At Weeks 4, 8, 16, 48 and 96)
- Absolute Value of CDAI Score Through Week 96(Baseline up to Week 96)
- Change From Baseline in CDAI Score Through Week 96(Up to Week 96)
- Percentage of Participants Achieving PRO-2 Remission at Weeks 4, 8, 16, 48, and Week 96(At Weeks 4, 8, 16, 48, and Week 96)
- Percentage of Participants Achieving Inflammatory Bowel Disease Questionnaire (IBDQ) Remission at Weeks 48 and 96(At Week 48 and Week 96)
- Percentage of Participants Achieving IBDQ Response at Weeks 48 and 96(Baseline, at Weeks 48 and 96)
- Absolute Value of IBDQ Through Week 96(Baseline up to Week 96)
- Change From Baseline in IBDQ Score Through Week 96(Up to Week 96)
- Change from Baseline in Urgency Numeric Rating Scale (UNRS) Through Week 96(Baseline up to Week 96)
- Percentage of Participants Achieving C-reactive Protein (CRP) Normalization at Weeks 4, 8, 16, 48, and Week 96(Baseline, at Weeks 4, 8, 16, 48, and Week 96)
- Percentage of Participants Achieving >=50% Improvement of CRP Response From Baseline at Weeks 4, 8, 16, 48, and 96(Baseline, at Weeks 4, 8, 16, 48, and 96)
- Percentage of Participants Achieving fCal Normalization at Weeks 4, 8, 16, 48, and 96(Baseline, at Weeks 4, 8, 16, 48, and 96)
- Percentage of Participants Achieving >=50% Improvement of fCal Response From Baseline at Weeks 4, 8, 16, 48, and 96(Baseline, at Weeks 4, 8, 16, 48, and 96)
- Change From Baseline in CRP and fCal Levels Over Time(Baseline, Weeks 4, 8, 16, 32, 48, and 96)
- Values of CRP and fCal Levels Over Time(Baseline, Weeks 4, 8, 16, 32, 48, and 96)
- Number of Participants with Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TSAEs) Through Week 48(Up to Week 48)
研究者
研究点 (141)
Loading locations...
相似试验
已完成
3 期
An Efficacy and Safety of Guselkumab in Participants With Palmoplantar PustulosisPalmoplantar PustulosisNCT02641730Janssen Pharmaceutical K.K.159
已完成
3 期
A Study Evaluating the Efficacy and Safety of Guselkumab Administered Subcutaneously in Participants With Active Psoriatic Arthritis Including Those Previously Treated With Biologic Anti -Tumor Necrosis Factor (TNF) Alpha Agent(s)Arthritis, PsoriaticNCT03162796Janssen Research & Development, LLC383
已完成
3 期
A Study Evaluating the Efficacy and Safety of Guselkumab Administered Subcutaneously in Participants With Active Psoriatic ArthritisArthritis, PsoriaticNCT03158285Janssen Research & Development, LLC741
进行中（未招募）
3 期
A Study of Guselkumab in Participants With Active Psoriatic ArthritisNCT04882098Janssen Research & Development, LLC1,054
已完成
3 期
Guselkumab in Active Psoriatic Arthritis Participants With Inadequate Response/Intolerance to One Prior Anti-TNF Alpha AgentArthritis, PsoriaticNCT04936308Janssen Research & Development, LLC453