A Study of Ustekinumab (STELARA) in Chinese Participants With Moderately to Severely Active Crohn's Disease

Crohn Disease Clinical Trial

Official title:

A Phase 4, Single Arm, Open-Label, 52-Week, Multicenter Study to Evaluate the Safety and Efficacy of Ustekinumab (STELARA), an Anti-Interleukin-12/23 Monoclonal Antibody, in Chinese Participants With Moderately to Severely Active Crohn's Disease

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05029921
• Other study ID #: CR109023
• Secondary ID: CNTO1275CRD4030
• Status: Active, not recruiting
• Phase: Phase 4
• Start date: December 10, 2021
• Est. completion date: August 22, 2025

Study information

• Verified date: March 2024
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the clinical and endoscopic efficacy and safety of ustekinumab in Chinese participants with moderately to severely active Crohn's disease.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 182
• Est. completion date: August 22, 2025
• Est. primary completion date: May 28, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Have Crohn's disease (CD) or fistulizing Crohn's disease of at least 3 months duration, with colitis, ileitis, or ileocolitis, confirmed in the past by radiography, histology, and/or endoscopy
• Have moderately to severely active CD, defined as a baseline Crohn's disease activity index (CDAI) score of greater than or equal to (>=) 220 and less than or equal to (<=) 450, and either: a. Mean daily stool frequency (SF) count >3, based on the unweighted CDAI component of the number of liquid or very soft stools or b. Mean daily abdominal pain (AP) score >1, based on the unweighted CDAI component of AP
• Have endoscopic evidence of active ileocolonic CD as assessed by central endoscopy reading at the screening endoscopy, defined as a screening simple endoscopic score for crohn's disease (SES-CD) score >=6 (or >=4 for participants with isolated ileal disease), based on the presence of ulceration in at least 1 of the 5 ileocolonic segments, resulting in the following specified ulceration component scores: a. a minimum score of 1 for the component of "size of ulcers"; and b. a minimum score of 1 for the component of "ulcerated surface"
• A woman of childbearing potential must have a negative highly sensitive serum (beta-human chorionic gonadotropin [beta-hCG]) at screening and a negative urine pregnancy test at baseline
• Must sign an informed consent form (ICF) indicating that he or she understands the purpose of, and procedures required for, the study and is willing to participate in the study

Exclusion Criteria:

• Has complications of Crohn's disease such as symptomatic strictures or stenoses, 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 ustekinumab
• Has previously demonstrated lack of initial response (that is, primary nonresponders), responded initially but then lost response with continued therapy (that is, secondary nonresponders) to Vedolizumab
• Has a history of, or ongoing, chronic or recurrent infectious disease, including but not limited to, chronic renal infection, chronic chest infection (example, bronchiectasis), recurrent urinary tract infection (example, recurrent pyelonephritis or chronic non-remitting cystitis), or open, draining, or infected skin wounds or ulcers
• History of lymphoproliferative disease, including lymphoma, or signs and symptoms suggestive of possible lymphoproliferative disease, such as lymphadenopathy or splenomegaly or monoclonal gammopathy of undetermined significance
• Has a history of severe, progressive, or uncontrolled renal, genitourinary, hepatic, hematologic, endocrine, cardiac, vascular, pulmonary, rheumatologic, neurologic, psychiatric, or metabolic disturbances, or signs and symptoms thereof

Related Conditions & MeSH terms

• Crohn Disease

Intervention

Drug:
• Ustekinumab
Ustekinumab will be administered as an IV injection in induction phase and as a SC injection in maintenance phase.

Locations

Country	Name	City	State
China	Peking University Third Hospital	Beijing
China	The Military General Hospital of Beijing PLA	Beijing
China	The second Xiangya Hospital of Central South University	Changsha
China	Changzhou No 2 Peoples Hospital	Changzhou
China	West China Hospital Sichuan University	Chengdu
China	The First Affiliated Hospital of Fujian Medical University	Fuzhou
China	Guangzhou First Municipal People's Hospital	Guangzhou
China	The 6th Affiliated Hospital of Sun Yat-Sen Hospital	Guangzhou
China	The First Affiliated Hospital, Sun Yat-sen University	Guangzhou
China	Sir Run Run Shaw Hospital, Zhejiang University School of Medicine	Hangzhou
China	The Second Affiliated Hospital of Zhejiang University	Hangzhou
China	Anhui Province Hospital	Hefei
China	Huzhou central hospital	Huzhou
China	Jinhua municipal central hospital	Jinhua
China	The First Affiliated Hospital of NanChang University	Nanchang
China	Jiangsu Province Hospital	Nanjing
China	Zhongda Hospital Southeast University	Nanjing
China	Ningbo medical center lihuili hospital	Ningbo
China	Huashan Hospital Fudan University	Shanghai
China	Shanghai 10th Peoples Hospital	Shanghai
China	Shanghai East Hospital	Shanghai
China	Shengjing Hospital of China Medical University	Shenyang
China	Peking University Shenzhen Hospital	Shenzhen
China	The Second Hospital Affiliated To Suzhou University	Suzhou
China	Renmin Hospital of Wuhan University	Wuhan
China	Tongji Hospital, Tongji Medical College of HUST	Wuhan
China	Wuxi People s Hospital	Wuxi
China	Yangzhou First People's Hospital	Yangzhou
China	Affiliated Hospital of Zunyi Medical University	Zunyi

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants with Clinical Remission at Week 8 (Co-primary Endpoint)	Clinical remission is defined as a crohn's disease activity index (CDAI) score of less than (<) 150 (in general, CDAI score ranges from 0 to approximately 600; higher score indicates higher disease activities). CDAI will be assessed by collecting information on 8 different Crohn's disease-related variables: extra-intestinal manifestations, abdominal mass, weight, hematocrit, total number of liquid or very soft stools, abdominal pain [AP]/cramping, use of antidiarrheal drug(s) and/or opiates, and general well-being. The last 4 variables are scored over 7 days by the participant on a diary card that participants are to complete on a daily basis.	Week 8
Primary	Percentage of Participants with Endoscopic Response at Week 16 (Co-primary Endpoint)	Endoscopic response is defined as at least 50 percent (%) improvement from baseline in Simple Endoscopic Score for Crohn's Disease (SES-CD) score or SES-CD score less than or equal to (<=) 2. The SES-CD score is based on the evaluation of 4 endoscopic components (presence/size of ulcers, percentage of mucosal surface covered by ulcers, the percentage of affected surface, and presence/type of narrowing/strictures) across 5 ileocolonic segments. Each endoscopic component is scored from 0 to 3 for each segment, and a total score is derived from the sum of all the component scores (range, 0 [remission] to 56 [the most severe endoscopic activity]).	Week 16
Secondary	Percentage of Participants with Clinical Remission at Week 52 (Major Secondary Endpoint)	Percentage of participants with clinical remission at Week 52 will be reported.	Week 52
Secondary	Percentage of Participants with Patient-reported Outcome (PRO)-2 Remission at Week 8 (Major Secondary Endpoint: Co-endpoint)	PRO-2 remission is defined as an AP mean daily score at or below 1 (AP<=1) and a stool frequency (SF) mean daily score at or below 3 (SF<=3), and no worsening of AP or SF from baseline.	Week 8
Secondary	Percentage of Participants with Endoscopic Remission at Week 16 (Major Secondary Endpoint: Co-endpoint)	Endoscopic remission is defined as SES-CD score of <= 2. The SES-CD score is based on the evaluation of 4 endoscopic components (presence/size of ulcers, percentage of mucosal surface covered by ulcers, the percentage of affected surface, and presence/type of narrowing/strictures) across 5 ileocolonic segments. Each endoscopic component is scored from 0 to 3 for each segment, and a total score is derived from the sum of all the component scores (range, 0 [remission] to 56 [the most severe endoscopic activity]).	Week 16
Secondary	Percentage of Participants with Endoscopic Response at Week 52	Percentage of participants with endoscopic response at Week 52 will be reported.	Week 52
Secondary	Percentage of Participants with Endoscopic Remission at Week 52	Percentage of participants with endoscopic remission at Week 52 will be reported.	Week 52
Secondary	Percentage of Participants with Clinical Remission at Week 3	Percentage of participants with clinical remission at Week 3 will be reported.	Week 3
Secondary	Percentage of Participants with PRO-2 Remission at Weeks 3 and 52	Percentage of participants with PRO-2 remission at Weeks 3 and 52 will be reported.	Weeks 3 and 52
Secondary	Percentage of Participants with Clinical Response at Weeks 3, 8, and 52	Clinical response is defined as a CDAI score decrease greater than or equal to (>=) 100 from baseline. Participants with a baseline CDAI score of >=220 to <=248 points are considered to be in clinical response if a CDAI score of <150 is attained.	Weeks 3, 8, and 52
Secondary	Percentage of Participants with Clinical Remission at Week 52 (in Participants Induced into Clinical Remission with Ustekinumab at Week 8)	Percentage of participants with clinical remission at Week 52 (in participants induced into clinical remission with ustekinumab at Week 8) will be reported.	Week 52
Secondary	Percentage of Participants with Corticosteroid-free Remission at Week 52	Corticosteroid-free remission is defined as a CDAI score <150 and not taking any corticosteroids for at least 30 days or 90 days prior to Week 52.	Week 52
Secondary	Change from Baseline in C-reactive Protein (CRP) Concentration at Week 3, Week 8, and Week 52	Change from baseline in CRP concentration at Week 3, Week 8, and Week 52 will be reported.	Baseline, Week 3, Week 8, and Week 52
Secondary	Percentage of Participants with Normalization of CRP at Weeks 3, 8, and 52	Percentage of participants with normalization of CRP at Weeks 3, 8, and 52 with elevated CRP (>3.0 milligrams per liter [mg/L]) at baseline will be reported.	Weeks 3, 8, and 52
Secondary	Change from Baseline in Fecal Calprotectin Concentration at Week 8 and Week 52	Change from baseline in fecal calprotectin concentration at Week 8 and Week 52 will reported. Fecal Calprotectin will be monitored as an inflammatory biomarker measured by assay.	Baseline, Week 8, and Week 52
Secondary	Percentage of Participants with Normalization of Fecal Calprotectin at Weeks 8 and 52	Percentage of participants with normalization of fecal calprotectin at Weeks 8 and 52 with elevated fecal calprotectin (>250 milligrams per kilograms [mg/kg]) at baseline will be reported.	Weeks 8 and 52
Secondary	Percentage of Participants with Fistula Response at Weeks 8 and 52	Fistula response is defined as a >=50% reduction in the number of draining fistulas, among participants with 1 or more fistulas at baseline.	Weeks 8 and 52
Secondary	Percentage of Participants with Clinical Remission of Delayed Responders at Week 52	Percentage of participants with clinical remission of delayed responders at Week 52 will be reported. Delayed responders are participants who are not in clinical response to ustekinumab at Week 8 and achieve clinical response at Week 16.	Week 52
Secondary	Percentage of Participants with PRO-2 Remission of Delayed Responders at Week 52	Percentage of participants with PRO-2 remission of delayed responders at Week 52 will be reported.	Week 52
Secondary	Percentage of Participants with Clinical Response of Delayed Responders at Week 52	Percentage of participants with clinical response of delayed responders at Week 52 will be reported.	Week 52
Secondary	Percentage of Participants with Endoscopic Response of Delayed Responders at Week 52	Percentage of participants with endoscopic response of delayed responders at Week 52 will be reported.	Week 52
Secondary	Percentage of Participants with Endoscopic Remission of Delayed Responders at Week 52	Percentage of participants with endoscopic remission of delayed responders at Week 52 will be reported.	Week 52
Secondary	Change from Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Score at Week 8 and Week 52	IBDQ is a validated, 32-item, self-reported questionnaire for participants with IBD to evaluate PROs across 4 dimensions: bowel symptoms (loose stools, AP), systemic symptoms (fatigue, altered sleep pattern), social function (work attendance, need to cancel social events), and emotional function (anger, depression, irritability). Scores range from 32 to 224, with higher scores indicating better outcomes.	Baseline, Week 8 and Week 52
Secondary	Percentage of Participants with IBDQ Response at Weeks 8 and 52	Percentage of participants with IBDQ response (>=16-point improvement from baseline) at Weeks 8 and 52 will be reported.	Weeks 8 and 52
Secondary	Percentage of Participants with IBDQ Remission at Weeks 8 and 52	Percentage of participants with IBDQ remission (>170-point) at Weeks 8 and 52 will be reported.	Weeks 8 and 52
Secondary	Percentage of Participants Having any Crohn's Disease (CD)-related Emergency Room (ER)/Hospitalizations (Including Surgeries) Through Week 8 and Week 52	Percentage of participants having any CD-related ER/hospitalizations (including surgeries) through Week 8 and Week 52 will be reported.	Weeks 8 and 52
Secondary	Percentage of Participants Having any CD-related Surgery and Procedure Through Week 8 and Week 52	Percentage of participants having any CD-related surgery and procedure through Week 8 and Week 52 will be reported.	Weeks 8 and 52
Secondary	Change from Baseline in Each of 4 Impairments from Work Productivity and Activity Impairment Questionnaire in Crohn's Disease (WPAI-CD) at Week 8 and Week 52	The WPAI-CD is a validated instrument created as a patient-reported quantitative assessment of the amount of absenteeism, presenteeism, and daily activity impairment attributable to CD. The WPAI-CD consists of 6 questions to determine employment status, hours missed from work due to Crohn's disease, hours missed from work for other reasons, hours worked, the degree to which Crohn's disease affected work productivity while at work, and the degree to which Crohn's disease affected activities outside of work. Four scores are derived: percentage of absenteeism, percentage of presenteeism (reduced productivity while at work), an overall work impairment score that combines absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Each of the four scores ranges from 0 to 100, with higher scores indicate greater impairment.	Baseline, Week 8, and Week 52
Secondary	Percentage of Participants with a 7-point Change from Baseline in Each of 4 Impairments from WPAI-CD at Week 8 and Week 52	The WPAI-CD is a validated instrument created as a patient-reported quantitative assessment of the amount of absenteeism, presenteeism, and daily activity impairment attributable to CD. The WPAI-CD consists of 6 questions to determine employment status, hours missed from work due to Crohn's disease, hours missed from work for other reasons, hours worked, the degree to which Crohn's disease affected work productivity while at work, and the degree to which Crohn's disease affected activities outside of work. Four scores are derived: percentage of absenteeism, percentage of presenteeism (reduced productivity while at work), an overall work impairment score that combines absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Each of the four scores ranges from 0 to 100, with higher scores indicate greater impairment.	Baseline, Week 8, and Week 52