Safety and Efficacy of BMS-986165 Compared with Placebo in Subjects with Ulcerative Colitis
- Conditions
- MedDRA version: 20.1Level: LLTClassification code 10045365Term: Ulcerative colitisSystem Organ Class: 100000004856Therapeutic area: Diseases [C] - Immune System Diseases [C20]lcerative Colitis
- Registration Number
- EUCTR2018-004694-27-IT
- Lead Sponsor
- BRISTOL-MYERS SQUIBB INTERNATIONAL CORPORATIO
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 120
a) Documented diagnosis (endoscopic and histological) of UC at least 12 weeks prior to screening
b) Disease severity: moderate to severe active UC defined as an Adapted Mayo Score of 5 to 9 points, inclusive, that includes all of the following subscore values:
• An endoscopic subscore of >= 2 (screening endoscopy)
• A rectal bleeding subscore >= 1
• A stool frequency subscore of >= 2
c) Active UC extending >= 15 cm from the anal verge and confirmed by a screening/baseline colonoscopy/sigmoidoscopy prior to the randomization visit
d) Documentation of an inadequate response, loss of response, or intolerance to a treatment course of 1 or more of the following standard of care medications:
• 5- ASAs, such as mesalamine, sulfasalazine, olsalazine, or balsalazide
• CS, such as prednisone (or equivalent) or budesonide (or equivalent)
• Immunosuppressants, such as azathioprine (AZA), 6-mercaptopurine (6-MP), or methotrexate (MTX)
• Anti-tumor necrosis factor (TNF)-a agents, such as infliximab, adalimumab, or golimumab
• Integrin inhibitor, such as vedolizumab
Subjects currently using concomitant salicylates, probiotics, or oral CS (<= 20 mg prednisone or equivalent, <= 9 mg budesonide or equivalent) at stable doses prior to the randomization visit are eligible provided they are on stable doses for the specified time period.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 108
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 12
•Previous/current documented diagnosis of Crohn's disease, indeterminate colitis, ischemic colitis, or pseudomembranous colitis.
•Positive stool culture for enteric pathogens (ova and parasites, bacteria) or positive for Clostridium difficile (C. difficile) at screening. Subjects who show a C. difficile positive result during screening, may re-screen for the study after they have successfully completed therapy (as per institutional practice) and been resolved for at least 2 weeks prior to the start of rescreening. Investigator will be responsible for clinically assessing eligibility.
•Current or recent (within 12 weeks prior to the randomization visit) evidence of fulminant colitis, abdominal abscess, toxic megacolon, or bowel perforation.
•History or evidence of any extensive colonic resection, subtotal or total colectomy, with or without presence of a stoma or ileoanal pouch. Current need for, or anticipated need for, surgical intervention for UC during the study.
•History of diverticulitis within 60 days prior to the randomization visit (previous diverticulitis that has been successfully treated with a local standard course of antimicrobial therapy is permitted; however, the course of antimicrobial therapy must be completed at least 30 days prior to the randomization visit).
•Current colonic adenomas or dysplasia or past confirmed colonic dysplasia that has not been eradicated (subjects who have had UC > 8 years should have had a colonoscopy to screen for dysplasia within 1 year prior to the randomization visit, or this can be performed as part of screening colonoscopy). A subject with prior history of adenomatous polyps will be eligible if the polyps have been completely removed (documented) and the subject is free of polyps at baseline.
•Prior exposure to treatment with TYK2 inhibitors.
•Prior lack of response to anti-12/23 p40 antibodies (such as ustekinumab or briakinumab) or anti-IL-23 p19 antibodies (such as guselkumab, risankizumab, tildrakizumab, MEDI2070, LY3074828).
•Failure or loss of response to janus kinase (JAK) inhibitors, such as tofacitinib.
•Nonresponders (ie, inadequate response and/or loss of response defined in APPENDIX 5) to > 2 biologic agents (eg, anti-TNF agents or vedolizumab) for the treatment of UC.
•Use of other investigational agents within 12 weeks or 5 half-lives prior to the randomization visit.
•Use of topical rectal treatment with 5-ASA or CS within 2 weeks prior to the randomization visit.
•Current use of CS at a dose of > 20 mg/day for prednisone or equivalent or > 9 mg/day for budesonide or equivalent.
•Use of immunosuppressants (AZA, 6-MP, or MTX) within 4 weeks prior to the randomization visit.
•Use of a biologic agent within 8 weeks or 5 half-lives, whichever is longer, prior to the randomization visit
oFecal transplant is considered as investigational” biologic agent and the appropriate washout period must be 8 weeks or 5 half-lives (if known), whichever is longer.
Please, refer to the Protocol for the full list of exclusion criteria
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: - To assess the effect of BMS-986165 on clinical remission at the end of the induction period<br>- To assess the safety and tolerability of BMS-986165 in subjects with moderate to severe UC;Secondary Objective: - To assess the effect of BMS-986165 on clinical response through the end of the induction period<br>- To assess the effect of BMS 986165 on endoscopic response at the end of the induction period<br>- To assess the effect of BMS-986165 on endoscopic remission at the end of the induction period;Primary end point(s): Clinical remission per Adapted Mayo Score;Timepoint(s) of evaluation of this end point: Week 12
- Secondary Outcome Measures
Name Time Method Secondary end point(s): • Clinical response<br>• Endoscopic response<br>• Endoscopic remission;Timepoint(s) of evaluation of this end point: Week 12