Phase 3 study of MLN0002 (300 mg) in treatment of ulcerative colitis
- Conditions
- lcerative colitis
- Registration Number
- JPRN-jRCT2080222353
- Lead Sponsor
- TAKEDA PHARMACEUTICAL COMPANY LTD.
- Brief Summary
Refer to conclusions of "Adverse Events" and "Primary Outcome Measures" sections.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- completed
- Sex
- All
- Target Recruitment
- 292
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 <10 mg/day due to recurrence during gradual dose reduction (oral or IV).
- Intolerance: Participants who were unable to receive continuous treatment due to adverse reactions (e.g., Cushing's syndrome, osteopenia/osteoporosis, hyperglycaemia, insomnia, infection).
Immunomodulators (azathioprine [AZA] or 6- mercaptopurine [6-MP])
- Refractory: Participants whose response was inadequate after treatment for >=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
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) within 13 days before the first dose of the study drug. Participants who have used these drugs for at least 14 days before the first dose of the study drug, and who changed dosage of or discontinued these drugs within 13 days before the first dose of the study drug.
7. Participants who have received 5-ASA, corticosteroid enemas/suppositories, corticosteroid IV infusion, oral corticosteroid at >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
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method