Safety and Efficacy of BMS-986165 Compared with Placebo in Subjects with Ulcerative Colitis

• Register: EUCTR
• Last refreshed on: 25 November 2019
• Main ID: EUCTR2018-004694-27-HU
• Date of registration: 06/05/2019
• Prospective Registration: Yes
• Primary sponsor: Bristol-Myers Squibb International Corporation
• Public title: Safety and Efficacy of BMS-986165 Compared with Placebo in Subjects with Ulcerative Colitis
• Scientific title: A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study of the Safety and Efficacy of BMS-986165 in Subjects with Moderate to Severe Ulcerative Colitis
• Date of first enrolment: 25/06/2019
• Target sample size: 120
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2018-004694-27
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, Canada, Czech Republic, Germany, Hungary, Italy, Japan, Korea, Republic of, Poland, Russian Federation, Spain, Switzerland, United Kingdom, United States

Contacts

• Name: GCT-SU
• Affiliation: Bristol-Myers Squibb International Corporation

• Name: GCT-SU
• Affiliation: Bristol-Myers Squibb International Corporation

Key inclusion & exclusion criteria

Inclusion criteria:
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

Exclusion criteria:
a) Previous/current documented diagnosis of CD, indeterminate colitis, ischemic colitis, pseudomembranous colitis.
b) Current or recent evidence of fulminant colitis, abdominal abscess, toxic megacolon, or bowel perforation.
c) History or evidence of any extensive colonic resection, subtotal or total colectomy, with or without presence of a stoma or ileoanal pouch.
d) History of diverticulitis within 60 days prior to the randomization visit
e) Current colonic adenomas or 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 at baseline.
f) Current or recent gastrointestinal disease, including gastrointestinal surgery, that could impact the absorption of study treatment, or current or recent gastrointestinal resections.
g) Women who are pregnant or breastfeeding.
h) Any major illness/condition or evidence of an unstable clinical condition, or local active infection/infectious
i) Any major surgery (requiring general anesthesia) within the last 30 days prior to the randomization visit
j) 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
k) Cancer or history of cancer or lymphoproliferative disease within the previous 5 years
l) 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.
m) Acute coronary syndrome and/or any history of significant cerebrovascular disease within 24 weeks before screening.
n) Female subjects with a breast cancer screen suspicious for malignancy, and in whom the possibility of malignancy cannot be reasonably excluded
o) Significant blood loss (> 500 mL) or blood transfusion within 4 weeks prior to the randomization visit.
p) Inability to tolerate oral medication.
q) Inability to undergo venipuncture and/or tolerate venous access.
r) Drug or alcohol abuse.
s) Inability to comply with restrictions and prohibited treatments, as listed in Section 6.7.
t) Previous exposure to BMS-986165/ TYK2 inhibitors in any study.
u) Prior lack of response to anti-12/23 p40 antibodies or anti-IL-23 p19 antibodies
v) Failure or loss of response to JAK inhibitors
w) Nonresponders to > 2 biologic agents for the treatment of UC.
x) Use of other investigational agents within 12 weeks or 5 half-lives, whichever is longer, prior to the randomization visit.
y) Use of topical rectal treatment with 5-ASA or CS within 2 weeks prior randomization visit.
z) Current use of CS at a dose of > 20 mg/day for prednisone or equivalent or > 9 mg/day for budesonide or equivalent.
aa) Use of immunosuppressants within 4 weeks prior to the randomization visit.
bb) Use of a biologic agent within 8 weeks or 5 half-lives, whichever is longer, prior to the randomization visit
cc) Previous stem cell transplantation
dd) Receipt of either lymphocyte apheresis or selective monocyte, granulocyte apheresis (eg, Cellosobra®) is prohibited within 12 months prior to the randomization visit.
ee) Use of therapeutic enema or suppository, other than required for ileocolonoscopy, within 7 days prior to the randomization visit.
ff) Receipt of tube feeding, defined formula diets, or total p

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Ulcerative Colitis
MedDRA version: 20.1 Level: LLT Classification code 10045365 Term: Ulcerative colitis System Organ Class: 100000004856

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Intervention(s)

Product Name: BMS-986165
Product Code: BMS-986165
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: BMS-986165
CAS Number: 1609392-27-9
Other descriptive name: BMS986165
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 6-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: week 12

Secondary Objective: - To assess the effect of BMS-986165 on clinical response through the end of the induction period
- To assess the effect of BMS 986165 on endoscopic response at the end of the induction period
- 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

Main Objective: - To assess the effect of BMS-986165 on clinical remission at the end of the induction period
- To assess the safety and tolerability of BMS-986165 in subjects with moderate to severe UC

Secondary Outcome(s)

Secondary end point(s): • Clinical response
• Endoscopic response
• Endoscopic remission

Timepoint(s) of evaluation of this end point: week 12

Secondary ID(s)

2018-004694-27-GB

IM011024

Source(s) of Monetary Support

Bristol Myers-Squibb International Corporation

Ethics review

Status: Approved
Approval date:
Contact: