Crohn's Disease MedDRA version: 20.0 Level: PT Classification code 10011401 Term: Crohn's disease System Organ Class: 10017947 - Gastrointestinal disorders MedDRA version: 20.0 Level: LLT Classification code 10011398 Term: Crohn's System Organ Class: 10017947 - Gastrointestinal disorders
Conditions
Interventions
Product Name: BMS-986165
Product Code: BMS-986165
Pharmaceutical Form: Capsule
INN or Proposed INN: BMS-986165
CAS Number: 1609392-28-0
Current Sponsor code: BMS-986165
Other descriptive name: BMS9861
Sponsors
Bristol-Myers Squibb international Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Signed Written Informed Consent a) Willing to participate in the study and sign the ICF. b) Willing and able to complete all study-specific procedures and visits. 2) Type of Subject and Target Disease Characteristics a) to d) Not applicable per Global Revised Protocol v3.0 e) Documented diagnosis of CD for at least 3 months prior to screening, including ileal, colonic, or ileo-colonic disease distribution, confirmed by: • Source: Medical records with report of a colonoscopy with ileal intubation (ileocolonoscopy), which shows features consistent with CD, as determined by the procedure performing physician, AND • Source: Medical record documentation of a histopathology report showing features consistent with CD, as determined by the local pathologist. Note: If a histopathology report is not available, histologic samples can be obtained at the screening endoscopy and sent to a local laboratory to confirm diagnosis of CD before proceeding to randomization. The screening endoscopy must show features consistent with CD. f) Must have active moderate to severe CD, as defined by: • CDAI score of 220 to 450 AND • PRO2: Average daily score for abdominal pain = 2 OR average daily number of very soft (loose) or liquid (watery) stools (BSS Type 6 or 7 only; see APPENDIX 18) = 4, as collected in the 7 most recent daily diary entries in the previous 14 days, AND • Evidence of active inflammation in at least 1 of the 5 ileocolonic segments (based on central reading) with total SES-CD = 6 or SES-CD = 4 if only isolated ileitis is present on baseline endoscopy g) Must have had an inadequate response, LOR, or intolerance to a standard treatment course of 1 or more of the following medications as below: • Oral 5-ASAs: (eg, mesalamine, sulfasalazine, olsalazine, balsalazine) at or above the approved label dose (or per local standard of care) for induction therapy for at least 6 weeks • Oral corticosteroids: Prednisone = 40 mg/day or equivalent for 2 weeks, or 2 failed attempts to taper oral corticosteroids below prednisone or equivalent 10 mg daily, or a relapse within 3 months of discontinuing corticosteroids • Intravenous (IV) corticosteroids: hydrocortisone = 400 mg/day or equivalent for at least 1 week • Immunomodulators: AZA = 1.5 mg/kg/day, 6-MP = 0.75 mg/kg/day, MTX = 15 mg/week, or as per Institutional Practice/Country-approved label or guideline, for at least 12 weeks. At institutions that utilize thiopurine levels in clinical practice: AZA or 6-MP prescribed for at least 12 weeks with at least 1 demonstration of therapeutic thiopurine metabolite levels. Note: subjects with defined NUDT15 or TPMT mutations who experience intolerance to thiopurines at lower doses than those listed above may be eligible for this study. This should be discussed with the medical monitor on a case-by-case basis. • Biologics: (eg, infliximab, adalimumab, certolizumab pegol, vedolizumab, natalizumab, ustekinumab) as defined in APPENDIX 4. Subjects can be included if treatment with a biologic was stopped due to primary or secondary nonresponse, or were intolerant to treatment, as defined in APPENDIX 4 3) Age and Reproductive Status a) Men and women aged 18 to 75 years inclusive at the time of screening b) Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of beta-human chorionic gonadotropin) within 24 hours prior to the start of study treatment. c) Women must not be breastfeedi
Exclusion criteria
Exclusion criteria: 1)Target Population a)Severe or fulminant colitis that is likely to require surgery or hospitalization b)Presence of a diagnosis of alternative forms of colitis (infectious, inflammatory including ulcerative colitis, malignant, toxic, indeterminate, etc) other than CD c)N/A per PAM v3.0 d)History of intra-abdominal abscess within the last 60 days •Previous intra-abdominal abscess that has been drained and successfully treated with a local standard course of antimicrobial therapy is permitted (the course must be completed at least 60 days prior to Day 1) e) History of diverticulitis within the last 60 days • Previous diverticulitis that has been successfully treated with a local standard course of antimicrobial therapy is permitted. (the course must be completed at least 60 days prior to Day 1) f) Receiving tube feeding, defined formula diets, or total parenteral alimentation g) Current colonic dysplasia or past colonic dysplasia that has not been definitively treated h) History of infectious (bacterial, viral, fungal, parasitic, etc.) colitis within past 30 days; must be fully treated to rescreen i) Use of therapeutic enema or suppository, other than required for ileocolonoscopy, within 7 days prior to screening or during the Screening Period j) N/A per PAM v3.0 k) N/A per PAM v3.0 l) Previous exposure to BMS-986165 in any study m) N/A per PAM v5.0 n) N/A per PAM v3.0 o) N/A per PAM v5.0 p) Prior treatment with specific lymphocyte-depleting agents, such as alemtuzumab and rituximab, are prohibited within 12 months prior to the first dose of study treatment during the Induction Period. q) Receipt of either lymphocyte apheresis or selective monocyte, granulocyte apheresis (eg, Cellsorba™) is prohibited within 12 months prior to the first dose of study treatment during the Induction Period r)Previous treatment with investigational agents within 4 weeks or 5 half-lives (whichever is longer) prior to the first dose of study treatment during the Induction Period. Subjects treated with investigational agents 4 to 12 weeks prior to the first dose of study treatment must be discussed with the medical monitor. s)Previous stem cell transplantation, (except local stem cell therapy to treat perianal fistulae (eg, Alofisel® [darvadstrocel]). Please discuss on a case by case basis with the medical monitor. t)Presence of a stoma, gastric or ileoanal pouch, previous proctocolectomy or total colectomy, or symptomatic, stenosing disease that is likely to confound efficacy assessment (eg, symptomatic CD-related stricture), abscess or suspected abscess, pouchitis, short bowel syndrome, or history of bowel perforation. In addition, subjects with colonic or ileal strictures that are not passable via colonoscope that the endoscopist normally uses in clinical practice, or strictures in the ileum or ileocecal valve that are fibrotic in nature, will be excluded. 2) Other Medical Conditions and History a) Women who are pregnant or breastfeeding b) Any major illness/condition or evidence of an unstable clinical condition (eg, renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, immunologic, psychiatric, or local active infection/infectious illness) that, in the investigator’s judgment, will substantially increase the risk to the subject if he or she participates in the study c) Any major surgery within the last 30 days before the first dose of study treatment, or any surgery planned during the course of the study d) N/A per PAM v3.0 e) Female s
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • Objective: To assess the effect of BMS-986165 on clinical remission and endoscopic response at the end of the Induction Period (Week 12 [Day 85]);Primary end point(s): •Co-primary endpoints: o Proportion of subjects achieving clinical remission at Week 12, and o Proportion of subjects achieving endoscopic response at Week 12, both at a population level.;Secondary Objective: • Objective: To assess the effect of BMS-986165 on clinical response at end of the Induction Period • Objective: To assess the effect of BMS-986165 on PRO 2 remission at the end of the Induction period • Objective: To assess the effect of BMS-986165 on gut mucosal disease activity by endoscopy at the end of the Induction Period ;Timepoint(s) of evaluation of this end point: 12 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The exploratory and safety objectives and endpoints are summarized in Section 4. ;Timepoint(s) of evaluation of this end point: 12, 52 and 104weeks | — |
Countries
Australia, Belgium, Brazil, Canada, China, Czechia, Denmark, France, Germany, Hungary, Ireland, Israel, Italy, Japan, Korea, Republic of, Mexico, Netherlands, Poland, Portugal, Romania, Russian Federation, Spain, Switzerland, Taiwan, United Kingdom, United States
Contacts
Public ContactGCT-SU
Bristol-Myers Squibb International Corporation
Outcome results
None listed