A Phase 2/3, Randomized, Double-blind, Placebo- and Active-controlled, Parallel-group, Multicenter Protocol to Evaluate the Efficacy and Safety of Guselkumab in Participants With Moderately to Severely Active Crohn's Disease
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 1,409
- 试验地点
- 1,083
- 主要终点
- GALAXI 1: Change From Baseline in the Crohn's Disease Activity Index (CDAI) Score at Week 12
研究概览
简要总结
The purpose of this study is to evaluate the clinical efficacy (GALAXI 1), clinical and endoscopic efficacy (GALAXI 2 and GALAXI 3) and safety of guselkumab in participants with Crohn's disease.
详细描述
This program consists of 3 separate studies: a 48-week Phase 2 dose-ranging study (GALAXI 1) and two 48-week Phase 3 confirmatory studies (GALAXI 2 and GALAXI 3). In Phase 2, safety and efficacy of guselkumab dose regimens will be evaluated to support the selection of induction and maintenance dose regimens for confirmatory evaluation in Phase 3. Participants who complete the 48-week Phase 2 or Phase 3 studies may be eligible to enter the long term extension (LTE). Throughout the 3 studies, efficacy, pharmacokinetic, biomarkers, and safety will be assessed.
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
- •Have Crohn's disease (CD) or fistulizing Crohn's disease 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
- •Have moderate to severe CD as assessed by CDAI, stool frequency (SF), and abdominal pain (AP) scores, and Simple Endoscopic Score for Crohn's Disease (SES-CD)
- •Have screening laboratory test results within the protocol specified parameters
- •A female participant of childbearing potential must have a negative urine pregnancy test result at screening and baseline
- •Demonstrated intolerance or inadequate response to conventional or to biologic therapy for CD
排除标准
- •Current diagnosis of ulcerative colitis or indeterminate colitis
- •Has complications of Crohn's disease, such as symptomatic strictures or stenoses, short gut syndrome, or any other manifestation
- •Unstable doses of concomitant Crohn's disease therapy
- •Receipt of Crohn's disease approved biologic agents, investigational agents, or procedures outside of permitted timeframe as specified in the protocol
- •Any medical contraindications preventing study participation
研究组 & 干预措施
Phase 2 (GALAXI 1): Group 1 (Guselkumab)
Participants will receive guselkumab (Dose 1) by intravenous (IV) infusion, followed by guselkumab (Dose 2) by subcutaneous (SC) injection. Participants who are eligible and willing to continue guselkumab may enter the Long-Term Extension (LTE) phase and continue to receive guselkumab.
干预措施: Guselkumab Dose 1 (Drug)
Phase 2 (GALAXI 1): Group 1 (Guselkumab)
Participants will receive guselkumab (Dose 1) by intravenous (IV) infusion, followed by guselkumab (Dose 2) by subcutaneous (SC) injection. Participants who are eligible and willing to continue guselkumab may enter the Long-Term Extension (LTE) phase and continue to receive guselkumab.
干预措施: Guselkumab Dose 2 (Drug)
Phase 2 (GALAXI 1): Group 2 (Guselkumab)
Participants will receive guselkumab (Dose 3) by intravenous (IV) infusion, followed by guselkumab (Dose 2) by subcutaneous (SC) injection. Participants who are eligible and willing to continue guselkumab may enter the LTE phase and continue to receive guselkumab.
干预措施: Guselkumab Dose 2 (Drug)
Phase 3 (GALAXI 2 and 3): Group 4 (Placebo/Ustekinumab)
Participants will receive placebo administered by intravenous (IV) infusion. At Week 12, non-responders will receive active treatment (ustekinumab) administered by intravenous (IV) infusion followed by subcutaneous (SC) injection. Participants who are eligible and willing to continue placebo/ustekinumab may enter the LTE and continue to receive placebo/ustekinumab.
干预措施: Placebo (Drug)
Phase 2 (GALAXI 1): Group 3 (Guselkumab)
Participants will receive guselkumab (Dose 4) by intravenous (IV) infusion, followed by guselkumab (Dose 5) by subcutaneous (SC) injection. Participants who are eligible and willing to continue guselkumab may enter the LTE phase and continue to receive guselkumab.
干预措施: Guselkumab Dose 4 (Drug)
Phase 2 (GALAXI 1): Group 3 (Guselkumab)
Participants will receive guselkumab (Dose 4) by intravenous (IV) infusion, followed by guselkumab (Dose 5) by subcutaneous (SC) injection. Participants who are eligible and willing to continue guselkumab may enter the LTE phase and continue to receive guselkumab.
干预措施: Guselkumab Dose 5 (Drug)
Phase 2 (GALAXI 1): Group 5 (Placebo/Ustekinumab)
Participants will receive placebo administered by intravenous (IV) infusion. At Week 12, non-responders will receive active treatment (Ustekinumab) administered by intravenous (IV) infusion followed by subcutaneous (SC) injection. Participants who are eligible and willing to continue placebo/ustekinumab may enter the LTE and continue to receive placebo/ustekinumab.
干预措施: Placebo (Drug)
Phase 2 (GALAXI 1): Group 5 (Placebo/Ustekinumab)
Participants will receive placebo administered by intravenous (IV) infusion. At Week 12, non-responders will receive active treatment (Ustekinumab) administered by intravenous (IV) infusion followed by subcutaneous (SC) injection. Participants who are eligible and willing to continue placebo/ustekinumab may enter the LTE and continue to receive placebo/ustekinumab.
干预措施: Ustekinumab (Drug)
Phase 2 (GALAXI 1): Group 4 (Ustekinumab)
Participants will receive ustekinumab by intravenous (IV) infusion, followed by subcutaneous (SC) injection. Participants who are eligible and willing to continue ustekinumab may enter the LTE and continue to receive ustekinumab.
干预措施: Ustekinumab (Drug)
Phase 3 (GALAXI 2 and 3): Group 1 and Group 2 (Guselkumab)
Participants will receive guselkumab by intravenous (IV) infusion, followed by guselkumab by subcutaneous (SC) injection. Participants who are eligible and willing to continue guselkumab may enter the LTE phase and continue to receive guselkumab.
干预措施: Guselkumab (Drug)
Phase 3 (GALAXI 2 and 3): Group 4 (Placebo/Ustekinumab)
Participants will receive placebo administered by intravenous (IV) infusion. At Week 12, non-responders will receive active treatment (ustekinumab) administered by intravenous (IV) infusion followed by subcutaneous (SC) injection. Participants who are eligible and willing to continue placebo/ustekinumab may enter the LTE and continue to receive placebo/ustekinumab.
干预措施: Ustekinumab (Drug)
Phase 2 (GALAXI 1): Group 2 (Guselkumab)
Participants will receive guselkumab (Dose 3) by intravenous (IV) infusion, followed by guselkumab (Dose 2) by subcutaneous (SC) injection. Participants who are eligible and willing to continue guselkumab may enter the LTE phase and continue to receive guselkumab.
干预措施: Guselkumab Dose 3 (Drug)
Phase 3 (GALAXI 2 and 3): Group 3 (Ustekinumab)
Participants will receive ustekinumab by intravenous (IV) infusion, followed by subcutaneous (SC) injection. Participants who are eligible and willing to continue ustekinumab may enter the LTE phase and continue to receive ustekinumab.
干预措施: Ustekinumab (Drug)
结局指标
主要结局
GALAXI 1: Change From Baseline in the Crohn's Disease Activity Index (CDAI) Score at Week 12
时间窗: Baseline and Week 12
The multi-item CDAI score assessed severity of illness by collecting information on 8 different Crohn's disease-related variables (extraintestinal manifestations, abdominal mass, weight, hematocrit, use of antidiarrheal drug(s) and/or opiates, total number of liquid or very soft stools, abdominal pain/cramps, and general well-being). The last 3 variables were scored over 7 eligible days by the participant on a diary card. The total CDAI score ranged from 0 to 600 in general: higher score indicated higher disease activities. A decrease in total CDAI score over time indicates improvement in disease activity. Baseline was defined as the last observation prior to or at the date of the first study intervention.
Global: GALAXI 2: Percentage of Participants With Both Clinical Response at Week 12 and Clinical Remission at Week 48
时间窗: Weeks 48
Clinical response was defined as a decrease from baseline (BL) in CDAI score greater than or equal to (\>=) 100 points or CDAI score \<150. Clinical remission was defined as a CDAI score \<150. The multi-item CDAI score assessed severity of illness by collecting information on 8 different Crohn's disease-related variables (extraintestinal manifestations, abdominal mass, weight, hematocrit, use of antidiarrheal drug(s) and/or opiates, total number of liquid or very soft stools, abdominal pain/cramps, and general well-being). The last 3 variables were scored over 7 eligible days by the participant on a diary card. The total CDAI score ranged from 0 to 600 in general: higher score indicated higher disease activities. A decrease in total CDAI score over time indicates improvement in disease activity.
Global: GALAXI 2: Percentage of Participants With Both Clinical Response (CR) at Week 12 and Endoscopic Response (ER) at Week 48
时间窗: Weeks 48
CR: decrease from BL in CDAI score \>=100/\<150. ER: \>=50% improvement from BL in SES-CD score/SES-CD score \<=2. CDAI(8 variables):extraintestinal manifestations, abdominal mass, weight, hematocrit, use of antidiarrheal drug(s) and/or opiates, total number of liquid/soft stools, abdominal pain/cramps, general well-being. Last 3 variables scored over 7 eligible days by participant on diary. Total CDAI score ranged:0-600(in general):higher score=higher disease activities. Decrease in total CDAI score over time=improvement in disease. SES-CD evaluated 4 endoscopic components (presence \& size of ulcer, extent of ulcerated surface, extent of affected surface, presence \& type of narrowing) across 5 ileocolonic segments (ileum; right, left \& transverse colon; rectum) each scored 0(best) to 3(worst) except narrowing component for which maximum total score (that is, stricturing) was 11 points. SES-CD score: sum of all component scores(all segments) ranged:0-56, higher scores=more severe disease.
Global: GALAXI 3: Percentage of Participants With Both Clinical Response at Week 12 and Clinical Remission at Week 48
时间窗: Weeks 48
Clinical response was defined as a decrease from baseline in CDAI score \>= 100 points or CDAI score \<150. Clinical remission was defined as a CDAI score \<150. The multi-item CDAI score assessed severity of illness by collecting information on 8 different Crohn's disease-related variables (extraintestinal manifestations, abdominal mass, weight, hematocrit, use of antidiarrheal drug(s) and/or opiates, total number of liquid or very soft stools, abdominal pain/cramps, and general well-being). The last 3 variables were scored over 7 eligible days by the participant on a diary card. The total CDAI score ranged from 0 to 600 in general: higher score indicated higher disease activities. A decrease in total CDAI score over time indicates improvement in disease activity.
Global: GALAXI 3: Percentage of Participants With Both Clinical Response (CR) at Week 12 and Endoscopic Response (ER) at Week 48
时间窗: Weeks 48
CR: decrease from BL in CDAI score \>=100/\<150. ER: \>=50% improvement from BL in SES-CD score/SES-CD score \<=2. CDAI(8 variables):extraintestinal manifestations, abdominal mass, weight, hematocrit, use of antidiarrheal drug(s) and/or opiates, total number of liquid/soft stools, abdominal pain/cramps, general well-being. Last 3 variables scored over 7 eligible days by participant on diary. Total CDAI score ranged:0-600(in general):higher score=higher disease activities. Decrease in total CDAI score over time=improvement in disease. SES-CD evaluated 4 endoscopic components (presence \& size of ulcer, extent of ulcerated surface, extent of affected surface, presence \& type of narrowing) across 5 ileocolonic segments (ileum; right, left \& transverse colon; rectum) each scored 0(best) to 3(worst) except narrowing component for which maximum total score (that is, stricturing) was 11 points. SES-CD score: sum of all component scores(all segments) ranged:0-56, higher scores=more severe disease.
Regional: GALAXI 2: Percentage of Participants With Clinical Remission at Week 12
时间窗: Week 12
Clinical remission was defined as a CDAI score \<150. The multi-item CDAI score assessed severity of illness by collecting information on 8 different Crohn's disease-related variables (extraintestinal manifestations, abdominal mass, weight, hematocrit, use of antidiarrheal drug(s) and/or opiates, total number of liquid or very soft stools, abdominal pain/cramps, and general well-being). The last 3 variables were scored over 7 eligible days by the participant on a diary card. The total CDAI score ranged from 0 to 600 in general: higher score indicated higher disease activities. A decrease in total CDAI score over time indicates improvement in disease activity.
Regional: GALAXI 2: Percentage of Participants With Endoscopic Response at Week 12
时间窗: Week 12
Endoscopic response was defined as \>=50% improvement from baseline in SES-CD score or SES-CD score \<=2. SES-CD evaluated 4 endoscopic components (presence and size of ulcer, extent of ulcerated surface, extent of affected surface, presence and type of narrowing) across 5 ileocolonic segments (ileum, right colon, transverse colon, left colon, rectum), each scored 0 (best) to 3 (worst) except narrowing component for which maximum total score (that is, stricturing) was 11 points. Total SES-CD score: sum of all component scores across all segments, ranged: 0 to 56, higher scores = more severe disease.
Regional: GALAXI 3: Percentage of Participants With Clinical Remission at Week 12
时间窗: Week 12
Clinical remission was defined as a CDAI score \<150. The multi-item CDAI score assessed severity of illness by collecting information on 8 different Crohn's disease-related variables (extraintestinal manifestations, abdominal mass, weight, hematocrit, use of antidiarrheal drug(s) and/or opiates, total number of liquid or very soft stools, abdominal pain/cramps, and general well-being). The last 3 variables were scored over 7 eligible days by the participant on a diary card. The total CDAI score ranged from 0 to 600 in general: higher score indicated higher disease activities. A decrease in total CDAI score over time indicates improvement in disease activity.
Regional: GALAXI 3: Percentage of Participants With Endoscopic Response at Week 12
时间窗: Week 12
Endoscopic response was defined as \>=50% improvement from baseline in SES-CD score or SES-CD score \<=2. SES-CD evaluated 4 endoscopic components (presence and size of ulcer, extent of ulcerated surface, extent of affected surface, presence and type of narrowing) across 5 ileocolonic segments (ileum, right colon, transverse colon, left colon, rectum), each scored 0 (best) to 3 (worst) except narrowing component for which maximum total score (that is, stricturing) was 11 points. Total SES-CD score: sum of all component scores across all segments, ranged: 0 to 56, higher scores = more severe disease.
次要结局
- GALAXI 1: Percentage of Participants With Clinical-Biomarker Response at Week 12(At Week 12)
- GALAXI 1: Percentage of Participants With Endoscopic Response at Week 12(At Week 12)
- Global: GALAXI 2 and 3: Percentage of Participants With Clinical Response at Week 4(At Week 4)
- Global: GALAXI 2 and 3: Percentage of Participants With Clinical Remission at Week 12(At Week 12)
- Global: GALAXI 2 and 3: Percentage of Participants With Endoscopic Response at Week 12(At Week 12)
- Global: GALAXI 2 and 3: Percentage of Participants With Fatigue Response at Week 12(At Week 12)
- Global: GALAXI 2 and 3: Percentage of Participants With Both Clinical Remission and Endoscopic Response at Week 12(At Week 12)
- Global: GALAXI 2 and 3: Percentage of Participants With Endoscopic Remission at Week 12(At Week 12)
- Global: GALAXI 2 and 3: Percentage of Participants With Both Clinical Response at Week 12 and Corticosteroid-Free Clinical Remission at Week 48(At Week 48)
- Global: GALAXI 2 and 3: Percentage of Participants With Both Clinical Response at Week 12 and Endoscopic Remission at Week 48(At Week 48)
- Global: GALAXI 2 and 3: Percentage of Participants With Clinical Remission at Week 48(At Week 48)
- Global: GALAXI 2 and 3: Percentage of Participants With Endoscopic Response at Week 48(At Week 48)
- Global: GALAXI 2 and 3: Percentage of Participants With Both Clinical Remission and Endoscopic Response at Week 48(At Week 48)
- Global: GALAXI 2 and 3: Percentage of Participants With Endoscopic Remission at Week 48(At Week 48)
- Global: GALAXI 2 and 3: Percentage of Participants With Deep Remission at Week 48(At Week 48)
- Regional: GALAXI 2 and 3: Percentage of Participants With PRO-2 Remission at Week 12(At Week 12)
- Regional: GALAXI 2 and 3: Percentage of Participants With Fatigue Response at Week 12(At Week 12)
- Regional: GALAXI 2 and 3: Percentage of Participants With Endoscopic Remission at Week 12(At Week 12)
- Regional: GALAXI 2 and 3: Percentage of Participants With Corticosteroid-free Clinical Remission at Week 48(At Week 48)
- Regional: GALAXI 2 and 3: Percentage of Participants With Endoscopic Response at Week 48(At Week 48)
- Regional: GALAXI 2 and 3: Percentage of Participants With Endoscopic Remission at Week 48(At Week 48)
- Regional: GALAXI 2 and 3: Percentage of Participants With Clinical Remission at Week 48(At Week 48)
- Regional: GALAXI 2 and 3: Percentage of Participants With Durable Clinical Remission at Week 48(At Week 48)
- Regional: GALAXI 2 and 3: Percentage of Participants With PRO-2 Remission at Week 48(At Week 48)
- Regional: GALAXI 2 and 3: Percentage of Participants With Both Clinical Remission at Week 48 and Endoscopic Response at Week 48(At Week 48)
- Regional: GALAXI 2 and 3: Percentage of Participants With Corticosteroid-free Remission at Week 48(At Week 48)
- GALAXI 1: Percentage of Participants With Clinical Remission at Week 12(At Week 12)
- GALAXI 1: Percentage of Participants With Clinical Response at Week 12(At Week 12)
- GALAXI 1: Percentage of Participants With Patient-Reported Outcome (PRO) 2 Remission at Week 12(At Week 12)