Crohn's disease
Conditions
Sponsors
Takeda Pharmaceutical Company Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Participants aged 15 to 80 years (inclusive) at the time of consent 2. Participants with a diagnosis of small-intestinal, large-intestinal, or small-/large-intestinal Crohn's disease established based on the Revised Diagnostic Criteria for Crohn's disease issued by Research Group for Intractable Inflammatory Bowel Disease Designated as Specified Disease by the Ministry of Health, Labor and Welfare of Japan (2012) at least 3 months before the start of administration of study drug 3. Participants with baseline Crohn's Disease Activity Index (CDAI) score of 220 to 450 (inclusive) and meeting at least one of the followings - C-reactive protein (CRP)at screening test is above 0.30 mg/dL - Participants with irregular or semicircular ulcers or multiple aphthae (10 or more) observed over an extensive area of the small or large intestine on endoscopy or imaging test within the 4 months before the start of administration of study drugs - Participants with longitudinal ulcers or a cobblestone appearance observed in the small or large intestine on endoscopy or imaging test within 4 months before the start of administration of study drugs 4. In case of the participants who meet any of the following criteria; participants with >= 8-year history of extensive or limited colitis, participants aged >= 50 years, or participants with a first-degree family history of colon cancer, those whom the complication of colon cancer or dysplasia was ruled out by total colonoscopy at the start of study drug administration (Or the results from total colonoscopy performed within 1 year before giving consent are available). 5. Participants meeting the criteria for treatment failure below with at least one of the following agents received within the previous 5 year period before giving consent. a. Corticosteroids - Resistance - Dependence - Intolerance b. Immunomodulators (azathioprine, 6-mercaptopurine or methotrexate) - Refractory - Intolerance c. Anti-TNF alpha antibodies - Inadequate response - Loss of response - Intolerance
Exclusion criteria
Exclusion criteria: 1. Participants with an evidence of or suspected abdominal abscess 2. Participants with a history of subtotal or total colectomy 3. Participants who have had a resection of the small intestine in at least 3 locations or have a diagnosis of short bowel syndrome 4. Participants with ileostomy, colostomy, or internal fistula, or severe intestinal stenosis 5. Participants who started 5-aminosalicylic acid oral drug or probiotics treatment, antimicrobials to treat Crohn's disease, or 30 mg/day or less of oral corticosteroids within 13 days before initiation of study drug administration. If these drugs were used within 14 days before initiation of study drug administration, the dosage must have been changed or their use discontinued within 13 days before the initiation of study drug administration. 6. Participants who have received 5-aminosalicylic acid or corticosteroid enemas/suppositories, intravenous corticosteroid injections, or more than 30 mg/day of oral corticosteroids, medications for diarrhea-predominant irritable bowel syndrome, or Chinese herbal medicine for the treatment of Crohn's disease (e.g., Daikenchuto) within 13 days before initiation of study drug administration 7. Participants who have received azathioprine, 6-mercaptopurine, or methotrexate within 27 days before initiation of study drug administration. However, this shall not apply to participants who have received these drugs for 83 or more days before initiation of the study drug administration and continued the steady dose administration of the drugs for 27 or more days before initiation of the study drug administration 8. Participants who have received cyclosporin, tacrolimus, tofacitinib or any study drugs for treatment of ulcerative colitis within 27 days before initiation of the study drug administration 9. Participants who have received adalimumab within 27 days before initiation of study drug administration or any biological drugs other than adalimumab within 55 days before initiation of the study drug administration. Topical administration (such as intraocular implantation for treatment of age-related maculopacy) is allowed 10. Participants who have received any live vaccinations within 27 days before initiation of study drug administration 11. Participants who have undergone intestinal resection within 27 days before initiation of study drug administration or those anticipated to require intestinal resection during the study 12. Participants who have received leukocytapheresis or granulocyte apheresis within 27 days before initiation of the study drug administration 13. Participants who have received intravenous hyperalimentation or total enteral nutrition within the 20 days before initiation of the study drug administration. Or participants who are fasted. 14. Participants who have received enteral nutrition at > 900 kcal/day or started enteral nutrition at <= 900 kcal/day within the 20 days before initiation of the study drug administration. Participants receiving 900 kcal/day or less of enteral nutrition for at least 21 days before initiation of the study drug administration and whom these dosage was changed or the medications were discontinued within 20 days before initiation of the study drug administration 15. Participants with evidence of adenomatous colonic polyps that need to be removed at the start of study drug administration 16. Participants with a history or an complication of dysplasia of the small or large intestine
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| efficacy Induction phase: Crohn's Disease Activity Index (CDAI)-100 response at Week 10 Time Frame: At Week 10 Reported data will be percentage of participants randomized to the induction phase with a decrease from baseline of at least 100 points in the CDAI score at Week 10. CDAI is scoring system for the Assessment of Crohn's Disease Activity. Index values of 150 and below are associated with quiescent disease; values above that indicate active disease. efficacy Maintenance Phase: Clinical remission at Week 60 Time Frame: At Week 60 Reported data will be percentage of participants randomized to the maintenance phase with clinical remission (CDAI score =3.0 U/L x upper limit of normal (ULN), AST (GOT) >3.0 U/L x ULN, Total Bilirubin >2.0 mg/dL x ULN, Amylase >2.0 (U/L) x ULN are considered markedly abnormal. | — |
Secondary
| Measure | Time frame |
|---|---|
| efficacy Induction phase: Clinical remission at Week 10 Time Frame: At Week 10 Reported data will be percentage of participants randomized to the induction phase with clinical remission (CDAI score =<150) at Week 10. CDAI is scoring system for the Assessment of Crohn's Disease Activity. Index values of 150 and below are associated with quiescent disease; values above that indicate active disease. efficacy Induction phase: Changes in C-reactive protein (CRP) values Time Frame: From baseline to Week 10 Summary statistics of C-reactive protein (CRP) values at each evaluation time point in the subpopulation of participants randomized to the induction phase with a baseline CRP value exceeding 0.30 mg/dL efficacy Maintenance Phase: CDAI-100 response at Week 60 Time Frame: At Week 60 Reported data will be percentage of participants randomized to the maintenance phase with a decrease from baseline of at least 100 points in the CDAI score at Week 60. CDAI is scoring system for the Assessment of Crohn's Disease Activity. Index values of 150 and below are associated with quiescent disease; values above that indicate active disease. efficacy Maintenance Phase: Durable clinical remission Time Frame: From Week 14 to Week 60 Reported data will be percentage of participants randomized to the maintenance phase with clinical remission (CDAI score =< 150) at least 80 percent of the scheduled visits, including Week 60. CDAI is scoring system for the Assessment of Crohn's Disease Activity. Index values of 150 and below are associated with quiescent disease; values above that indicate active disease. efficacy Maintenance Phase: Corticosteroid-free clinical remission at Week 60 Time Frame: At Week 60 Reported data will be percentage of participants randomized to the maintenance phase who are not using the corticosteroids used at initiation of study drug administration and who show clinical remission (CDAI score =< 150) at Week 60. CDAI is scoring system for the Assessment of Crohn's Dise | — |
Countries
Japan
Outcome results
None listed