A Phase 3, Open-label, Multicenter Study to Evaluate the Safety and Efficacy of Guselkumab in Participants With Moderately to Severely Active Crohn's Disease
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 38
- 试验地点
- 43
- 主要终点
- Number of Participants With Treatment-emergent Serious Adverse Events (TESAEs)
研究概览
简要总结
The purpose of this study is to evaluate the safety of Guselkumab in participants with Crohn's disease.
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
盲法说明
Open Label
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 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
- •Have moderate to severe CD as assessed by CDAI components of stool frequency (SF), and abdominal pain (AP) scores, and endoscopic evidence
- •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
- •Has complications of CD, 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 time frame as specified in the protocol
- •Prior exposure to p40 inhibitors or p19 inhibitors
- •Any medical contraindications preventing study participation
研究组 & 干预措施
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 Long-term extension (LTE) phase and continue to receive guselkumab.
干预措施: Guselkumab (Drug)
结局指标
主要结局
Number of Participants With Treatment-emergent Serious Adverse Events (TESAEs)
时间窗: From baseline (Week 0) up to Week 48
Number of participants with TESAEs were reported. TEAEs are AEs with onset during the intervention phase or that are a consequence of a pre-existing condition that had worsened since baseline. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
时间窗: From baseline (Week 0) up to Week 48
Number of participants with TEAEs were reported. An adverse event (AE) was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. Treatment-emergent AEs (TEAEs) were AEs with onset during the intervention phase or that were a consequence of a pre-existing condition that had worsened since baseline. All TEAEs including serious and non-serious AEs were reported.
Number of Participants With Treatment-emergent Adverse Events of Special Interest (TEAESI)
时间窗: From baseline (Week 0) up to Week 48
Number of participants with TEAESI was reported. Active tuberculosis (TB) or malignancies were considered as TEAESIs. TEAESIs were AESIs with onset during the intervention phase or that are a consequence of a pre-existing condition that had worsened since baseline.
Number of Participants With TEAEs of Infections
时间窗: From baseline (Week 0) up to Week 48
Number of participants with TEAEs of infections were reported. TEAEs are AEs with onset during the intervention phase or that are a consequence of a pre-existing condition that had worsened since baseline.
Number of Participants With Treatment-emergent Abnormalities in Hematology Laboratory Parameters
时间窗: From baseline (Week 0) up to Week 48
Number of participants with treatment-emergent abnormalities in hematology laboratory parameters were reported. Laboratory tests included in hematology were hemoglobin, lymphocytes, neutrophils, platelet count, Total WBC (white blood cell) Count. National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) toxicity grades were Grade 1 (Mild), Grade 2 (Moderate), Grade 3 (Severe), Grade 4 (Potentially Life-Threatening). TE abnormalities are laboratory abnormalities with onset during the intervention phase or that are a consequence of a pre-existing condition that had worsened since baseline.
Number of Participants With TEAEs of Injection-site Reactions
时间窗: From baseline (Week 0) up to Week 48
Number of participants with TEAEs of injection-site reactions were reported. A significant injection-site reaction was defined as an adverse reaction that was manifested through 1 or more of the following symptoms: significant bruising, erythema, hemorrhage, irritation, pain, pruritus at the site of injection. TEAEs are AEs with onset during the intervention phase or that are a consequence of a pre-existing condition that has worsened since baseline.
Number of Participants With TEAEs Temporally Associated With Infusion
时间窗: From baseline (Week 0) up to Week 48
Number of participants with TEAEs temporally associated with infusion were reported. TEAEs are AEs with onset during the intervention phase or that are a consequence of a preexisting condition that had worsened since baseline.
Number of Participants With Treatment-emergent Abnormalities in Chemistry Laboratory Parameters
时间窗: From baseline (Week 0) up to Week 48
Number of participants with treatment-emergent abnormalities in chemistry laboratory parameters were reported. Laboratory parameters included in clinical chemistry were albumin, corrected calcium, creatinine, glucose, potassium, sodium. NCI-CTCAE) toxicity grades were Grade 1 (Mild), Grade 2 (Moderate), Grade 3 (Severe), Grade 4 (Potentially Life-Threatening). TE abnormalities are laboratory abnormalities with onset during the intervention phase or that are a consequence of a pre-existing condition that had worsened since baseline.
Number of Participants With TEAEs of Suicidal Ideation, Suicidal Behavior, or Self-Injurious Behavior Without Suicidal Intent
时间窗: From baseline (Week 0) up to Week 48
TEAEs are AEs with onset during the intervention phase or that are a consequence of a pre-existing condition that had worsened since baseline. The Columbia-suicide severity rating scale (C-SSRS) defined was 5 subtypes of suicidal ideation and 4 possible suicidal behaviors, as well as non-suicidal self-injurious behavior and completed suicide. The C-SSRS was an investigator-administered questionnaire: 1) No suicidal ideation or behaviors (including self-injurious behavior without suicidal intent): No further action was needed; 2) Suicidal ideation levels 1-3 or non-suicidal self-injurious behavior; participant risk is assessed by the investigator. 3) Suicidal ideation levels 4 or 5 or any suicidal behavior: participant risk assessed and referral to a mental health professional. If no events qualify for scores of 1 to 10, score of 0 was assigned (0= "no event that can be assessed on the basis of C-SSRS"). Higher scores indicated greater severity.
Number of Participants With Clinically Significant Treatment-emergent Abnormalities in Vital Signs
时间窗: From baseline (Week 0) up to Week 48
Number of participants with clinically significant treatment-emergent abnormalities in vital signs were reported. Vital signs included weight, pulse rate, temperature, respiratory rate, systolic blood pressure, and diastolic blood pressure. TEAEs are AEs with onset during the intervention phase or that are a consequence of a pre-existing condition that had worsened since baseline.
Number of Participants With Concomitant Medications for Crohn's Disease
时间窗: From screening (Week -8) up to Week 48
Number of participants with concomitant medications for Crohn's disease were reported.
次要结局
- Number of Participants With Clinical Remission Through Week 48(Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48)
- Number of Participants With Clinical Response Through Week 48(Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48)
- Number of Participants With Anti-Guselkumab Antibodies Through Week 48(From Week 0 through Week 48)
- Number of Participants With Patient-reported Outcome(s) (PRO)-2 Remission Through Week 48(Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48)
- Serum Concentation of Guselkumab(Predose at Weeks 0, 4, 8, 12, 16, 20, 24, 32, 40, 48 and 1 hour post dose at Weeks 0, 4, 8)
- Change From Baseline in Simple Endoscopic Score for Crohn's Disease (SES-CD) Score at Week 48(Baseline (Week 0) and Week 48)
- Number of Participants With Neutralizing-Guselkumab Antibodies Through Week 48(From Week 0 through Week 48)
- Change From Baseline in Inflammatory PD Marker: Fecal Calprotectin (FC) Levels(Baseline (Week 0), Weeks 4, 8, 12, 24, and 48)
- Change From Baseline in Crohn's Disease Activity Index (CDAI) Score at Week 48 by Serum Guselkumab Concentration Quartiles at Week 48(At Week 48)
- Change From Baseline in Inflammatory Pharmacodynamic (PD) Marker: C-reactive Protein (CRP) Concentration(Baseline (Week 0), Weeks 4, 8, 12, 16, 20, 24, 32, 40 and 48)
- Number of Participants in Clinical Response at Week 48 by Serum Guselkumab Concentration Quartiles at Week 48(At Week 48)
- Number of Participants in Clinical Remission at Week 48 by Serum Guselkumab Concentration Quartiles at Week 48(At Week 48)
- Number of Participants in Endoscopic Response at Week 48 by Serum Guselkumab Concentration Quartiles at Week 48(At Week 48)
- Number of Participants in Endoscopic Remission at Week 48 by Serum Guselkumab Concentration Quartiles at Week 48(At Week 48)
- Change From Baseline in the Average Daily Prednisone-equivalent (P.Eq) Oral Corticosteroid Dose (Excluding Budesonide) Through Week 48 Among Participants Receiving Oral Corticosteroids Other Than Budesonide at Baseline(Baseline (Week 0), Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48)
- Number of Participants Not Receiving Concomitant Corticosteroids at Week 48 Among Participants Receiving Concomitant Corticosteroids at Baseline(At Week 48)
- Number of Participants Not Receiving Concomitant Corticosteroids for at Least 30 Days Prior to Week 48 Among Participants Receiving Concomitant Corticosteroids at Baseline(Up to Week 48)
- Number of Participants Not Receiving Concomitant Corticosteroids for at Least 90 Days Prior to Week 48 Among Participants Receiving Concomitant Corticosteroids at Baseline(Up to Week 48)