inflammation of the large intestine ulcers of the colon
Conditions
Interventions
Patients who have completed screening procedures (up to 28 days duration) and
met inclusion/exclusion criteria will be randomized on Day 1 of the treatment
period.
Patients will be randomized in a
blood, stool and urine collection for checking safety,
pharmacokinetics, and biomarkers, vital signs monitoring, endoscopy with
biopsies, ECG, additional efficacy assessments and the physician*s glo
and patient collection of PROs in daily electronic diaries.
After patients complete the first treatment period, they may be eligible to
enter the Open-label Extension Period: Subjects who are likel
Sponsors
Bristol-Myers Squibb
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1.) Type of Participant and Target Disease Characteristics a. A diagnosis of Ulcerative Colitis (UC) at least (>=) 3 months* duration prior to screening and source documents must include (i) an endoscopy report, which shows features consistent with UC, and (ii) a histopathology report showing features consistent with UC. If an endoscopy report is not available prior to screening, the screening endoscopy can be used to confirm the diagnosis. If a histopathology report is not available prior to screening, endoscopic biopsies can be obtained at the screening endoscopy (with appropriate consent) and sent to a local histopathology laboratory for reporting, to meet the criteria described above prior to randomization. b. UC disease distribution extending proximal to the rectum (ie, left-sided colitis or pancolitis) c. Moderately to severely active UC, defined by a modified Mayo score of 5 to 9 points inclusive, which includes all of the following: i. A stool frequency (SF) subscore of >= 2, and ii. A rectal bleeding (RB) subscore >= 1, and iii. An endoscopic (ES) subscore of >= 2 d. Must be up to date with surveillance for dysplasia and screening for colorectal neoplasia, according to local standard of care 2.) Age and Reproductive Status a. Males and Females, ages 18 (or local age of majority) to 65 years, inclusive, at the time of screening. b. Women who are not of child-bearing potential are exempt from contraception requirements. Female subjects must have documented proof that they are not of childbearing potential c. Women of Child Bearing Potential (WOCBP) must have a negative highly sensitive serum or urine pregnancy test. (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin) within 24 hours prior to the start of study treatment. If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. The participant must be excluded from participation if the serum pregnancy result is positive. d. A female subject is eligible to participate if she is not pregnant or breastfeeding and at least one of the following conditions applies: (1) Is not a WOCBP OR (2) a WOCBP and using a contraceptive method(s) as described in the protocol during the intervention period (at a minimum until after the last dose of study intervention) e. Males who are sexually active with WOCBP must agree to follow instructions for contraception as desribed in the protocol f. Azoospermic males are exempt from contraceptive requirements 3. ) Prior UC Medication Failure Inclusion Criteria a. Documentation of an inadequate response, loss of response, or intolerance to a treatment course of 1 or more of the following standard of care medications: i. Oral 5-aminosalicylic acids (5-ASAs) (eg, mesalamine, sulfasalazine, olsalazine, or balsalazide) ii. Corticosteroids (eg, prednisone or budesonide MMX) iii. Immunomodulators (eg, azathioprine [AZA], 6-mercaptopurine [6-MP], or methotrexate [MTX] iv. Anti-TNF agents (eg, infliximab, adalimumab, or golimumab) v. Integrin inhibitors (eg, vedolizumab) vi. Anti-IL-12/IL-23p40 antibodies (eg, ustekinumab): subjects can only be included if they were intolerant to tre
Exclusion criteria
Exclusion criteria: 1.) Medical Conditions a. Women who are pregnant or breastfeeding 2.) Ulcerative Colitis (UC) Exclusion Criteria a. UC involving the rectum only (UC proctitis). b. Current diagnosis of Crohn*s disease, indeterminate colitis, ischemic colitis or microscopic. c. Current or recent (within 12 weeks prior to randomization) evidence of fulminant UC (also known as acute severe UC) or toxic megacolon. d. Current or recent (within 12 weeks prior to randomization) evidence of bowel perforation or intra-abdominal abscess. e. Current or recent colonic diverticulitis. Subject must be adequately treated and off antibiotics for diverticulitis for 60 days prior to randomization. f. Current colonic adenomas or mucosal dysplasia i. A subject with adenomatous polyps may be eligible if the polyps have been completely removed or eradicated (documented). The subject must be free of polyps at randomization. ii. A subject with mucosal dysplasia may be eligible if the dysplasia has been completely removed/resected/eradicated (as applicable, documented), and the subject is free of dysplasia at randomization. This should be discussed with the BMS Medical Monitor/designee prior to screening iii. Subjects with a history of UC greater than (>) 8 years* duration (who have not had a colonoscopy in the prior 12 months) must have a full colonoscopy at screening. Subjects who require a colonoscopy to screen for dysplasia (based on local guidelines) must have a full colonoscopy at screening Subjects who require a colonoscopy to screen for colorectal cancer (based on local guidelines) must have a full colonoscopy at screening. 3.) Gastrointestinal (GI) Surgery Exclusion Criteria a. History or evidence of extensive colonic resection, subtotal or total colectomy, with or without a stoma or pouch. b. Current need for, or anticipated need for, surgical intervention for UC during the study. c. GI surgery within 3 months prior to randomization Subject must have adequate wound healing prior to randomization. 4.) Additional Gastrointestinal (GI) Exclusion Criteria a. Current or recent (within 12 weeks prior to randomization) GI disease that may confound efficacy assessment or any GI disease associated with poor absorption of the investigational product (for example, untreated celiac sprue, bile salt-mediated diarrhoea, or short bowel syndrome). b. Receiving enteral feeding, defined formula diets, or total parenteral alimentation. 5.) Immune and Infectious Disease Exclusion Criteria a. History of congenital or acquired immunodeficiency b. Known serious infection, defined as any infection requiring hospitalization or treatment with parenteral (intramuscular [IM] or IV) antimicrobial agents (eg, antibiotics, antiviral, antifungal, or antiparasitic agents) within 30 days of the first dose of study treatment. Completion of oral antimicrobial agents within 2 weeks of the first dose of study treatment. Antibiotics used to cover a procedure such as endoscopy would not exclude the subject. c. Current or recent (within 12 weeks prior to randomization) herpes zoster, herpes simplex, or influenza infection d. History of disseminated or complicated herpes zoster infect
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary objective of the study is to estimate the efficacy of BMS-986165 at Week 12 This will measured by the proportion of subjects in clinical response at Week 12 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary objectives of the study will be as follows: 1. to assess the safety and tolerability of BMS-986165. This will be measured by the Number and proportion of subjects experiencing Adverse Events (AE), Serious AEs, AEs leading to discontinuation from the study, and AEs of interest (AEI) throughout the study 2. to estimate the effect of BMS-986165 on inflammatory biomarkers. This will be measured by the change in baseline in biomarkers of inflammation over time. 3. To explore the efficacy of BMS-986165 at Week 12. This will be measured by: i. Proportion of subjects in clinical remission at Week 12 ii. Change from baseline in modified Mayo score at Week 12 iii. Change from baseline in individual subscores of the modified Mayo score at Week 12 iv. Change from baseline in the UC-100 score at Week 12 4. To explore the efficacy of BMS-986165 over time. This will be measured by: i. Change from baseline in the Stool Frequency (SF) and Rectal Bleeding (RB) subscores at over time ii. Change from baseline in the sum of the SF and RB subscores over time iii. Proportion of participants in symptomatic remission over time iv. Change from baseline in partial Mayo score over time 5. To explore the effect of BMS-986165 on the endoscopic appearance of the mucosa. This will be measured by: i. Change from baseline in the UC Endoscopic Index of Severity (UCEIS) score at Week 12 Ii. Proportion of subjects in endoscopic remission at Week 12 Iii. Proportion of subjects in endoscopic improvement at Week 12 Iv. Proportion of subjects with endoscopic response at Week 12 6. To explore the effect of BMS-986165 on the histological appearance of the mucosa. This will be measured by: i. Change from baseline in the Robarts Histopathology Index (RHI) at Week 12 Ii. Proportion of subjects in histologic improvement by Geboes score 7. To explore the efficacy of BMS-986165 at Week 52. This will be measured by: i. Proportion of subjects in clinical remission at Week 52 | — |
Countries
Netherlands
Outcome results
None listed