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-NL
- 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) 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 sta
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 CDrelated
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 & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 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]);Secondary Objective: •Objective: To assess the effect of BMS-986165 on clinical response at end of the Induction Period<br>•Objective: To assess the effect of BMS-986165 on PRO2 remission at the end of the Induction Period<br>•Objective: To assess the effect of BMS-986165 on gut mucosal disease activity by endoscopy at the end of the Induction Period<br>;Primary end point(s): •Co-primary endpoints:<br>o Proportion of subjects achieving clinical remission at Week 12, and<br>o Proportion of subjects achieving endoscopic response at Week 12,<br>both at a population level.;Timepoint(s) of evaluation of this end point: 12 weeks
- Secondary Outcome Measures
Name Time Method 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 104 weeks