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-DE
- Lead Sponsor
- Bristol-Myers Squibb international Corporation
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 239
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 screening, including ileal, colonic, or ileo-colonic diesease distribution, 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) stools (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 salicylatesaminosalicylates: (eg, mesalamine, sulfasalazine, olsalazine, balsalazine) at or above the approved label dose for induction therapy for at least 6 weeks prior to randomization,
• 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 10 mg 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, ustekinumab). Subjects can be included if treatment with a biologic was stopped due to primary or secondary nonresponse (responded initially but then lost response with continued therapy), or were intolerant to treatment.
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) to g) Not applicable per Global Revised Protocol v3.0
h) Azoospermic males are exempt from contraceptive requirements. WOCBP who are continuously not heterosexually active are also exempt from contraceptive requirements, and still must undergo pregnancy testing as described in this section.
i) Not applicable per Global Revised Protocol v3.0
j) Not applicable per Global Revised Protocol v5.0
k) Investigators shall counsel WOCBP and men who are sexually active with WOCBP, on the importance of pregnancy preve
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 UC, malignant, toxic, indeterminate, etc.) other than CD
c) N/A per PAM v3
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 60days prior to Day1)
e)History of diverticulitis within the last 60days
•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 d. prior to D. 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 30days; must be fully treated to rescreen
i) Use of therapeutic enema or suppository, other than required for ileocolonoscopy, within 7days prior to screening or during the Screening Period
j&k) N/A per PAM v3
l) Previous exposure to BMS-986165 in any study
m) N/A per PAM v5
n) N/A per PAM v3
o) N/A per PAM v5
p) 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
q) 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
r) Previous treatment with investigational agents within 4weeks or 5half-lives 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) Prev stem cell transplantation, (ex local stem cell therapy to treat perianal fistulae (eg, Alofisel® [darvadstrocel]). To dicuss case by case with MM.
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 sur
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<br>[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;Primary end point(s): Co-primary endpoints: <br>?Proportion of subjects achieving clinical remission at Week 12 and<br>?Proportion of subjects achieving endoscopic response at Week 12, both a population level<br>;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