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-DK
- Lead Sponsor
- Bristol-Myers Squibb International Corporation
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- 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 Characteristics
a) N/A
b) N/A
c) N/A
d) N/A
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 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 breastfeeding
d) N/A
e) N/A
f) N/A
g) N/A
h) Azoospermic males are exempt fr
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
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
k)N/A
l)Previous exposure to BMS-986165 in any study
m) N/A
n) N/A
o) N/A
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
e) Female subjects with a breast cancer screen suspicious for malignancy, and in whom the possibility of malign
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