Ulcerative colitis
Conditions
Interventions
Vedolizumab 300 mg, IV intravenous (IV) infusion, once at Weeks 0, 2, and 6 in the induction phase.
Generic name etc : MLN0002 (Vedolizumab)
INN of investigational material : Vedolizumab
Therapeutic c
Vedolizumab 300 mg, IV infusion, once at Weeks 14, 22, 30, 38, 46 and 54 in maintenance phase. Participants received vedolizumab in induction phase and achieved clinical response at Week 10 and were r
Vedolizumab placebo-matching, IV infusion, once at Weeks 14, 22, 30, 38, 46 and 54 in maintenance phase. Participants received vedolizumab in induction phase and achieved clinical response at Week 10
Sponsors
TAKEDA PHARMACEUTICAL COMPANY LTD.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. In the opinion of the investigator, a participant is capable of understanding and complying with protocol requirements. 2. A participant who is capable of entering the signature and the date on the informed consent by himself/herself or by the participant's legally acceptable representative, if applicable, prior to initiation of study procedures. 3. A participant aged 15 to 80 (inclusive) at the time of signing the informed consent (regardless of sexes). 4. A male participant, who has no sterilization history and whose female partner has child-bearing potential, who agreed with taking proper contraception during the period from the time of signing the informed consent form through 6 months after the last dose of study drug. 5. A female participant with child-bearing potential (having no history of sterilization or whose last menstruation was within 2 years) whose male partner is not receiving contraceptive treatment, and agreed to take proper contraception during the period from the time of signing on the informed consent form through 6 months after the last dose of the study drug. 6. Participants with diagnosis of total or left-sided UC based on the Revised Diagnostic Criteria for UC issued by "Research Group for Intractable Inflammatory Bowel Disease Designated as Specified Disease" by the Ministry of Health, Labor and Welfare (MHLW) of Japan (2012) at least 6 months before the start of administration of the study drug. 7. A participant with moderately or severely active UC as determined by baseline complete Mayo score of 6 to 12 (inclusive) with an endoscopic subscore of >=2. 8. Participants whose complication of colon cancer or dysplasia had to be ruled out by total colonoscopy at the start of the study drug administration (or the results from total colonoscopy performed within 1 year before giving consent are available), if participants met any of the following criteria; participants with >=8-year history of total or left-sided colitis, participants aged >=50 years, or participants with a first-degree family history of colon cancer. 9. Participants meeting the following treatment failure criteria with at least one of the following agents within 5 years before signing on the informed consent: Corticosteroids - Resistance: Participants whose response was inadequate after treatment of >=40 mg/day for >=1 week (oral or IV) or 30 to 40 mg/day for >=2 weeks (oral or IV). - Dependence: Participants for which it is difficult to reduce the dosage to =12 weeks. - Intolerance: Participants who were unable to receive continuous treatment due to adverse reactions (e.g., nausea/vomiting, abdominal pain, pancreatitis, liver function test abnormalities, lymphopenia, thiopurine S-methyltransferase genetic mutation, infection). TNF-alpha antagonist - Inadequate response: Participants whose response was inadequate after the induction therapy in the dosage described in the package insert. - Loss of response: Participants who had recurrence during the scheduled maintenance therapy after achievement of clinical response (those who withdrew for othe
Exclusion criteria
Exclusion criteria: 1. Participants whose partial Mayo score decrease by 3 points or more between screening and the start of study drug administration. 2. Participants having or suspected to have abdominal abscess or toxic megacolon. 3. Participants with a history of subtotal or total colectomy. 4. Participants with ileostomy, colostomy, fistula or severe intestinal stenosis. 5. Participants having a treatment history with natalizumab, efalizumab or rituximab. 6. Participants who started oral 5-ASA, probiotics, or oral corticosteroids (=30 mg/day, drugs for diarrhea-predominant irritable bowel syndrome, or Chinese herbal medicine for the UC treatment (eg, Daikenchuto) within 13 days before the first dose of the study drug. 8. Participants who have used an antidiarrheal drug for 4 or more consecutive days within 13 days before the first dose of the study drug or within 7 days before the first dose of the study drug. 9. Participants who have received AZA or 6-MP within 27 days before the first dose of the study drug However, this will not apply to participants who have used these drugs for 83 or more days before the first dose of the study drug and continued the steady dose administration of the drugs for 27 or more days before the first dose of the study drug. 10 .Participants who have received cyclosporine, tacrolimus, methotrexate, tofacitinib or any study drugs of low-molecular compound for UC treatment within 27 days before the first dose of the study drug. 11. Participants who have received adalimumab within 27 days before the first dose of the study drug or any biologic agents other than adalimumab within 55 days before the first dose of the study drug. However, this will not apply to participants who have topically received these drugs (eg., intraocular injection for treatment of age-related macular degeneration). 12. Participants who have received any live-vaccinations within 27 days before the first dose of the study drug. 13. Participants who underwent the enterectomy within 27 days before the first dose of the study drug or those anticipated to require an enterectomy during the study. 14. Participants who have received leukocytapheresis or granulocyte apheresis within 27 days before the first dose of the study drug. 15. Participants who have been infected with an intestinal pathogen including clostridium difficile or cytomegalovirus within 27 days before the first dose of the study drug. 16. Participants with evidence of adenomatous colonic polyps that need to be removed at the start of study drug administration. 17. Participants with a history or a complication of colonic mucosal dysplasia. 18. Participants suspected to have enteritis other than UC. 19. Participants indicated in the screening test as hepatitis B surface (HBs) antigen-positive or hepatitis C virus (HCV) antibody-positive. Participants indicated as hepatitis B core (HBc) antibody-positive or HBs antibody positive even though HBs antigen-negative However, the criteria will not apply to those with only HBs antibody-positive due to hepatitis B virus (HBV) vaccination, HBV-DNA-negati
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| efficacy Percentage of Participants with a Clinical Response at Week 10 in Induction Phase Timeframe: Week 10 Clinical response is defined as a reduction in complete Mayo score of >=3 points and >=30% from Baseline with an accompanying decrease in rectal bleeding subscore of >=1 point or absolute rectal bleeding subscore of =1 point. Mayo Score is a standard assessment tool to measure ulcerative colitis disease activity in clinical trials. The index consists of 4 subscores: rectal bleeding, stool frequency, findings on endoscopy, and physician's global assessment. Each subscore is scored on a scale from 0 to 3 and the complete Mayo score ranges from 0 to 12 (higher scores indicate greater disease activity). safety Number of Participants Who Experienced at Least One or More Treatment-Emergent Adverse Events (TEAEs) Timeframe: From baseline to 16 weeks after the last dose of study drug (Up to approximately 170 weeks) An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (e.g., a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. safety Number of Participants with TEAE Related to Body Weight Time Frame: From baseline to 16 weeks after the last dose of study drug (Up to approximately 170 weeks) safety Number of Participants with TEAE Related to Vital Signs Time Frame: From baseline to 16 weeks after the last dose of study drug (Up to approximately 170 weeks) Vital signs included body temperature (axilla), sitting blood pressure (after the participant has rested for at least 5 minutes), and pulse (bpm). safety Numbe | — |
Secondary
| Measure | Time frame |
|---|---|
| efficacy Percentage of Participants with Clinical Remission at Week 10 in Induction Phase Time Frame: Week 10 Clinical Remission is defined as a complete Mayo score of =1 point. Mayo Score is a standard assessment tool to measure ulcerative colitis disease activity in clinical trials. The index consists of 4 subscores: rectal bleeding, stool frequency, findings on endoscopy, and physician's global assessment. Each subscore is scored on a scale from 0 to 3 and the complete Mayo score ranges from 0 to 12 (higher scores indicate greater disease activity). efficacy Percentage of Participants with Mucosal Healing at Week 10 in Induction Phase Time Frame: Week 10 Mucosal healing is defined as a Mayo endoscopic subscore of ==3 points and >=30% from Baseline (Week 0) with an accompanying decrease in rectal bleeding subscore of >=1 point or absolute rectal bleeding subscore of =1 point at both Weeks 10 and 60. Mayo Score is a standard assessment tool to measure ulcerative colitis disease activity in clinical trials. The index consists of 4 subscores: rectal bleeding, stool frequency, findings on endoscopy, and physician's global assessment. Each subscore is scored on a scale from 0 to 3 and the complete Mayo score ranges from 0 to 12 (higher scores indicate greater disease activity). efficacy Percentage of Participants with Corticosteroid-Free Remission at Week 60 in Maintenance Phase Time Frame: Week 60 Clinical Remission is defined as a complete Mayo score of =1 point. Corticosteroid-free clinical remission is defined as participants using oral corticosteroids at baseline (Week 0) who discontinued corticosteroids and were in clinical remission at Week 60. Mayo Score is a standard assessment tool to measure ulcerative colitis disease activity in clinical trials. The index consists of 4 subscores: rectal bleeding, stool frequency, findings on endoscopy, and physician's global assessment. Each subscore is scored on a scale from 0 to 3 and the complete Mayo score ranges from 0 | — |
Countries
Japan
Outcome results
None listed