Safety and Efficacy of BMS-986165 Compared with Placebo in Subjects with Ulcerative Colitis
- Conditions
- lcerative ColitisMedDRA version: 20.1Level: LLTClassification code 10045365Term: Ulcerative colitisSystem Organ Class: 100000004856Therapeutic area: Diseases [C] - Immune System Diseases [C20]
- Registration Number
- EUCTR2018-004694-27-FR
- Lead Sponsor
- Bristol-Myers Squibb International Corporation
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 120
a) Documented diagnosis (endoscopic and histological) of UC of at least 3 months duration prior to screening
b) Active moderate to severe UC defined by a modified Mayo Score of 5 to 9 points, inclusive (modified Mayo score range = 0 to 9 points), which includes all of the following subscore:
• A stool frequency subscore of = 2 and
• A rectal bleeding (RB) subscore = 1, and
• An endoscopic (ES) subscore of = 2 (screening endoscopy)
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:
• Corticosteroids (eg: prednisone [or equivalent] or budesonide [or equivalent])
• Immunomodulatorrs (eg: azathioprine [AZA], 6-mercaptopurine [6-MP], or methotrexate [MTX])
• Anti-tumor necrosis factor-alpha (TNF-a) agents (eg: infliximab, adalimumab, or golimumab)
• Integrin inhibitors (eg: vedolizumab)
•Anti-IL-12/IL-23p40 antibodies (eg, ustekinumab); subjects can only be included if they were intolerant to treatment. Inadequate response or loss of response is exclusionary.
•Subjects currently using concomitant salicylates, probiotics, or oral Corticosteroid (= 20 mg prednisone or equivalent, = 9 mg budesonide MMX or equivalent) at stable doses prior to the randomization visit are eligible provided they are on stable doses for the time period specified in Section 6.7.2
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
a)Previous/current documented diagnosis of CD, indeterminate colitis, ischemic colitis, pseudomembranous colitis (other than associated with Clostridium difficile [C. difficile])
b)Stool positive for C. difficile toxin at screening visit; subjects may be rescreened 30 days after completion of an institutional standard of care course with antibiotics, and subsequent negative testing for C. difficile stool toxin and a C. difficile nucleic acid amplification test
c)Current or recent evidence of fulminant colitis, abdominal abscess, toxic megacolon, or bowel perforation
d)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
e)History of diverticulitis within 60 days prior to the randomization visit
f)Current colonic adenomas, dysplasia or past confirmed colonic dysplasia that has not been eradicated. 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 and without evidence of dysplasia on histology at randomization
g)Current or recent gastrointestinal disease, including gastrointestinal surgery which could impact the absorption of study treatment, or current or recent gastrointestinal resections
h)Receiving tube feeding, defined formula diets, or total parenteral alimentation
i)Women who are pregnant or breastfeeding
j)Any major illness/condition or evidence of an unstable clinical condition, or local activinfection/infectious illness that in the investigator’s judgment will substantially increase the risk to the subject if he or she participates in the study
k)Any major surgery (requiring general anesthesia) within the last 30 days prior to the randomization visit, or any other major surgery planned during the course of the study
l)History of bleeding disorders or recent use of anti-platelet or anti-thrombotic agents that in the investigator’s judgment preclude safely performing endoscopic procedures and biopsy
m)Cancer or history of cancer or lymphoproliferative disease within the previous 5 years
n)Class III or IV congestive heart failure, as classified by the New York Heart Association (NYHA) Functional Classification or any recent onset of heart failure resulting in NYHA Class III/IV symptoms
o)Acute coronary syndrome and/or any history of significant cerebrovascular disease within 24 weeks before screening
p)Female subjects with a breast cancer screen suspicious for malignancy, and in whom the possibility of malignancy cannot be reasonably excluded after additional clinical, laboratory, or other diagnostic evaluations
q)Significant blood loss (> 500 mL) or blood transfusion within 4 weeks prior to the randomization visit
r)Inability to tolerate oral medication
s)Inability to undergo venipuncture and/or tolerate venous access.
t)Drug or alcohol abuse as determined by the investigator within 6 months prior to Week 0 (Day 1)
u)Previous exposure to BMS-986165/ TYK2 inhibitors in any study.
v)Failure or loss of response to JAK inhibitors
w)Use of topical rectal treatment with 5-ASA or CS within 2 weeks prior randomization visit
x)Current use of CS at a dose of > 20 mg/day for prednisone or equivalent or > 9 mg/day for budesonide MMX or equivalent
y)Previous stem cell transplantation
z)Receipt of either lymphocyte apheresis or selectiv
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 at 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 (modified 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<br>;Timepoint(s) of evaluation of this end point: week 12