A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study of the Safety and Efficacy of BMS 986165 in Subjects with Moderate-to-Severe Crohn's Disease
- Conditions
- Crohn's DiseaseMedDRA version: 20.0Level: PTClassification code 10011401Term: Crohn's diseaseSystem Organ Class: 10017947 - Gastrointestinal disordersMedDRA version: 20.0Level: LLTClassification code 10011398Term: Crohn'sSystem Organ Class: 10017947 - Gastrointestinal disordersTherapeutic area: Diseases [C] - Immune System Diseases [C20]
- Registration Number
- EUCTR2017-001976-48-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
- 240
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 Characteristicsa) Documented diagnosis of CD of at least 3 months' duration, with colitis, ileitis, or ileocolitis, confirmed by:• Source: Medical records with report of an ileocolonoscopy (full colonoscopy with the intubation of terminal ileum) 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 no previous confirmation of diagnosis is available or if previous diagnosis is not deemed conclusive, at time of baseline endoscopy,histology must be performed and read locally to confirm diagnosis of CD before proceeding to randomization.b)Must have active moderate to severe CD, as defined by:
• CDAI score of 220 to 450 AND • PRO 2: Average daily score for abdominal pain >= 2 OR average daily number of very soft (loose)or liquid(watery)stool(BSS Type 6 or 7 only) >= 4, as collected in a 7-day diary, 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 c) Must have had an inadequate response, loss of response, or intolerance to a standard treatment course of 1 or more of the following standard of care medications as below:
• Oral CS: Prednisone 20 mg/day or equivalent for at least 2 weeks, and/or 2 failed attempts to taper oral CS below prednisone or equivalent 10mg daily
• IV Corticosteroids: hydrocortisone >= 400 mg/day or equivalent for at least 1 week,• Immunomodulators (AZA >= 2 mg/kg/day, 6-MP >= 1 mg/kg/day, MTX>= 25 mg/week, or documentation of a therapeutic concentration of 6 thioguanine nucleotide) for at least 12 weeks, or • Biologics (eg, infliximab, adalimumab, certolizumab pegol,vedolizumab, natalizumab). Subjects can be included if treatment with a biologic was stopped due to primary (eg, did not respond initially after treatment for at least 12 weeks at the approved dose) or secondary nonresponse (responded initially but then lost response with continued therapy), or were intolerant to treatment. d) This study permits the rescreening of a subject that has been deemed as ineligible (screen failure) during the Screening Period (ie, subject has not been randomized/has not been treated; Section 6.5). If re enrolled,the subject must be re-consented (ie, re-signing of the ICF) and rescreened (if outside the 28-day Screening Period window). Only 1 re enrollment per subject is permissible.3) Age and Reproductive Status
a) Men and women, aged 18 to 75 years old (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 breastfeeding d) WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study treatment(s) BMS 986165 (36 weeks) plus 5 half-lives of study treatment BMS 986165 (3 days) plus 30 days (duration of ovulatory cycle) for a total of 33 days post treatment completion. e) WOCBP who are not heterosexually acti
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) Presence of a stoma, gastric or ileoanal pouch, previous proctocolectomy or total colectomy, symptomatic, obstructive disease such as stenosis or obstructive strictures, abscess or suspected abscess, pouchitis, short
bowel syndrome, or history of bowel perforation
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 have 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 have 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) Prior treatment with specific lymphocyte-depleting agents, such as alemtuzumab, rituximab, and other agents such as ustekinumab, are prohibited within 12 months prior to the first dose of study treatment
during the Induction Period. Please note that lack of response to ustekinumab (as well as other anti-12/23 p40 antibodies) or anti-IL-23 p19 antibodies is criteria for exclusion (also see exclusion criterion 3.b).
k) Receipt of either lymphocyte apheresis or selective monocyte,granulocyte apheresis (eg, Cellsobra®) is prohibited within 12 months
prior to the first dose of study treatment during the Induction Period
l) Previous exposure to BMS-986165 in any study
m) Previous stem cell transplantation
n) Previous treatment with investigational agents within 12 weeks or 5 half-lives (whichever is longer) prior to the first dose of study treatment during the Induction Period
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method