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

Study Overview
=================
Brief 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.

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

Conditions
-----------------
Crohn Disease

Intervention / Treatment
-----------------
* Drug: Ustekinumab


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ustekinumab<br>Participants will receive a single dose of ustekinumab intravenously (IV) (weight-based dose approximating 6 milligrams per kilogram [mg/kg]) at Week 0. Participants with body weight less than or equal to (<=) 55 kg will receive ustekinumab IV of 260 mg, greater than (>) 55 kg and <=85 kg will receive ustekinumab IV of 390 mg, and >85 kg will receive ustekinumab IV of 520 mg at Week 0 in induction phase followed by ustekinumab 90 mg subcutaneously (SC) in maintenance phase from Week 8 to Week 52. For participants who achieve clinical response with ustekinumab induction dosing at Week 8, will continue to receive 90 mg ustekinumab SC every 12 weeks with final dose at Week 44. If these participants meet the criteria for loss of response from Week 16 to Week 40, dose can be adjusted to 90 mg every 8 weeks (q8w). Participants who are non-responders to ustekinumab at Week 8, and achieve clinical response at Week 16, will continue to receive ustekinumab 90 mg SC q8w from Week 16 to Week 48. | Drug: Ustekinumab<br>* Ustekinumab will be administered as an IV injection in induction phase and as a SC injection in maintenance phase.<br>* Other names: STELARA;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| Percentage of Participants with Endoscopic Response at Week 52 | Percentage of participants with endoscopic response at Week 52 will be reported. | Week 52 | 
| Percentage of Participants with Endoscopic Remission at Week 52 | Percentage of participants with endoscopic remission at Week 52 will be reported. | Week 52 | 
| Percentage of Participants with Clinical Remission at Week 3 | Percentage of participants with clinical remission at Week 3 will be reported. | Week 3 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 |