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

• Register: EUCTR
• Last refreshed on: 22 June 2020
• Main ID: EUCTR2017-001976-48-HU
• Date of registration: 05/07/2018
• Prospective Registration: Yes
• Primary sponsor: Bristol-Myers Squibb international Corporation
• Public title: 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
• Scientific title: 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 - LATTICE
• Date of first enrolment: 13/09/2018
• Target sample size: 144
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-001976-48
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 4
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Brazil, Canada, Czech Republic, Denmark, France, Germany, Hungary, Italy, Korea, Republic of, Mexico, Poland, Portugal, Romania, Spain, Switzerland, Taiwan, United Kingdom, United States

Contacts

• Name: GCT-SU
• Affiliation: Bristol-Myers Squibb International Corporation

• Name: GCT-SU
• Affiliation: Bristol-Myers Squibb International Corporation

Key inclusion & exclusion 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) N/A
b) N/A
c) N/A
d) N/A
e) Documented diagnosis of CD of at least 3 months’ duration, 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) 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 from contraceptive re
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
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) Previous stem cell transplantation
n) N/A
o) 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
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.
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 malignancy cannot be reasonably excluded after additional clinical, laboratory, or other diagnostic evaluations
f) Significant blood loss (> 500 mL) or blood transfusion within 4 weeks of study treatment administration
g) Inability to tolerate oral medication
h) Inability to undergo venipuncture and/or tolerate venous access
i) N/A
j) Any other sound medical, psychiatric, and/or social reason as determin

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

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

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Intervention(s)

Product Name: BMS-986165
Product Code: BMS-986165
Pharmaceutical Form: Capsule
INN or Proposed INN: BMS-986165
CAS Number: 1609392-28-0
Other descriptive name: BMS986165
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 3-
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: • Objective: To assess the effect of BMS-986165 on clinical remission and endoscopic response at the end of the Induction Period

Secondary Objective: • Objective: To assess the effect of BMS-986165 on endoscopic remission at Week 12 (Day 85)
• Objective: To assess the effect of BMS-986165 on clinical response at end of the Induction Period (Week 12 [Day 85])
• Objective: To assess the effect of BMS-986165 on clinical response through end of the Maintenance Period (Week 52 [Day 365])
• Objective: To assess the effect of BMS-986165 on clinical remission through the end of the Maintenance Period (Week 52 [Day 365])
• Objective: To endoscopically assess the effect of BMS-986165 on gut mucosal disease activity
• Objective: To assess the effect of BMS-986165 on deep remission

Primary end point(s): •Co-primary endpoints:
o Proportion of subjects achieving clinical remission, and
o Proportion of subjects achieving endoscopic response, at a population level.

Timepoint(s) of evaluation of this end point: 12 weeks

Secondary Outcome(s)

Secondary end point(s): The exploratory objectives and endpoints are summarized in Section 4.

Timepoint(s) of evaluation of this end point: 12 and 52 weeks

Secondary ID(s)

2017-001976-48-GB

IM011023

Source(s) of Monetary Support

Bristol-Myers Squibb Research and Development

Ethics review

Status: Approved
Approval date: 03/09/2018
Contact: