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A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study of the Safety and Efficacy of BMS-986165 in Subjects with Moderate to Severe Ulcerative Colitis

Safety and Efficacy of BMS-986165 in Subjects with Moderate to Severe Ulcerative Colitis (IM011-024)

131

Out of the 131 randomized subjects, 88 subjects were randomized to DEUC, of which 87 subjects received DEUC. Forty-three subjects were randomized to placebo, of which 42 subjects received placebo. The 2 subjects who did not receive treatment were randomized in error. Overall, the majority of randomizedsubjects were white (87.0%), male (58.8%), and in geographic region Rest of World (ie, outside of the US and Japan;77.1%). The median age of subjects was 40.0 years. There were imbalances between the 2 treatment groups in the categories of sex (more females in the DEUC group) and weight category (more subjects >= 90 kg in the DEUC group), but these were considered circumstantial and not likely to impact the study outcome. Baseline disease characteristics were generally similar across the 2 treatment groups and were representative of a population with moderate to severe UC. The mean duration of disease was approximately 8 years. The mean age at disease onset was 33.7 years. However, there was an imbalance between the groups in subjects with baseline modified Mayo score =< 7 (64.8% and 72.1%, for DEUC and placebo, respectively). The proportion of subjects with prior exposure to biologics and corticosteroids was similar between the treatment groups. A majority of subjects had no prior exposure to TNF inhibitor (TNFi) (71.8%), vedolizumab(86.3%), or TNFi + vedolizumab(89.3%).59.5%of subjects overall had no prior corticosteroid use. Prior exposure to corticosteroids and biologicsfor treatment of UC were stratification factors in this study. The number of DEUC subjects who were naive to prior biologic treatment for UC was 56 vs 57 per the IRT vs CRF, respectively; accordingly, the number of DEUC subjects with prior exposure to 1 biologic was 19 vs 18 per the IRT vs CRF, respectively.

A total of 131 subjects were randomized across 67 sites in 13 countries (Australia, Belgium, Czech Republic, France, Germany, Hungary, Italy, Japan, South Korea, Poland, Russia, the United Kingdom and the United States). The FPFV date was 01-Jul-2019, first patient first treatment (FPFT) date was 29-Jul-2019, and LPLV (for the Week 12 CSR) was 10-Jun-2021.The clinical DBL for this CSR occurred on 07-Sep-2021.

DEUC 6 mg BID was generally safe and well-tolerated in subjects with moderateto severeUC. Key safety results are as follows: - Overall, there was a higher frequency of AEs (all-causality and related) in the DEUC group compared with placebo. The most common treatment-related AEs observed in the DEUC group were rash (9.2%), acne (5.7%), upper abdominal pain and erythema (2.3% each).The majority of AEs during the induction periodwere mild to moderate in severity. - AEIs of skin-related events and influenza wereobserved in both groups. A higher frequency of skin-related AEIs was seen in the DEUC group compared with placebo. A similar frequency of influenza was observed in both groups. - The frequency of AEs leading to discontinuation was higher in the DEUC group compared with placebo. Most of these AEs were unrelated to study treatment. - The frequency of SAEs was higher in the DEUC group compared with placebo. Most SAEs were unrelated to study treatment. - During the induction period, there was one fatal case due to COVID-19-related pneumonia unrelated to study treatment in a subject in the DEUC group. - No safety concerns were identified based on the review of lab results. No DILI events were reported. There were no clinically meaningful changes or safety concerns for vital signs or ECG parameters.

The study did not meet its primary endpoint of clinical remission (modified Mayo score) at Week 12. A clinical remission rate of 14.8% was observed in the DEUC group, compared with 16.3% in the placebo group.

.A numerically greater proportion of subjects achieved clinical response and histologic improvement (secondary endpoints) in the DEUC group compared with placebo. Endoscopic response (secondary endpoint) in the DEUC group was numerically lower than that seen in the placebo group.Testing of the secondary endpoints was considered nominal. In the subgroup of subjects with prior exposure to biologics, DEUC-treated subjects had a numerically higher rate of clinical remission, clinical response, and endoscopic response compared with placebo treatment.

The study did not meet the primary endpoint of clinical remission (modified Mayo score) at Week 12, nor secondary endpoints. The clinical remission, endoscopic and clinical response rates in the biologic-exposed subgroup suggest that a proportion of patients would achieve meaningful benefit from DEUC. During the induction period, DEUC 6 mg BID had an acceptable safety profile and was generally well-tolerated in subjects with moderate to severe UC.

Feb. 17, 2025

No

https://cdn.clinicaltrials.gov/large-docs/16/NCT03934216/Prot_SAP_000.pdf

Sreih Antoine G.

Bristol-Myers Squibb

1-2-1 Otemachi, Chiyoda-ku, Tokyo

mg-jp-clinical_trial@bms.com

Sreih Antoine G.

Bristol-Myers Squibb

1-2-1 Otemachi, Chiyoda-ku, Tokyo

+81-120-093-507

MG-JP-RCO-JRCT@bms.com

completed

July. 31, 2019

Interventional

Randomized, parallel-group, treatment

treatment purpose

2

-Active UC extending >= 15 cm from the anal verge and confirmed by a screening/baseline colonoscopy/sigmoidoscopy prior to the randomization visit
-Documented diagnosis of UC of at least 3 months duration prior to screening
-Active moderate to severe UC, defined by a modified Mayo score of 5 to 9 points, inclusive (modified Mayo score range = 0 to 9 points), which includes all of the following subscore values:
A stool frequency (SF) subscore of >= 2, and
A rectal bleeding (RB) subscore >= 1, and
An endoscopic (ES) subscore of >= 2 (screening endoscopy)

-Previous/current documented diagnosis of CD, indeterminate colitis, ischemic colitis, or pseudomembranous colitis (other than associated with Clostridium difficile [C. difficile])
-Stool positive for C. difficile toxin at screening visit
-Current or recent (within 12 weeks prior to the randomization visit) evidence of fulminant colitis, abdominal abscess, toxic megacolon, or bowel perforation

Both

Ulcerative Colitis

BMS-986165:Specified Dose on Specified Days
Placebo:Specified Dose on Specified Days

Clinical Remission Response Rate at Week 12 calculated using a modified Mayo score with the following:
Stool Frequency (SF) sub score <= 1, with >= 1 point decrease from baseline, and Rectal Bleeding (RB) sub score = 0, and Endoscopic (ES) sub score <= 1 (modified, excludes friability)

-Clinical Response Rate at 12 Weeks defined as percentage of participants with a reduction in total Mayo Score and reduction in rectal bleeding subscore. It will be defined as the following:
A decrease from baseline in the modified Mayo score of >= 2 points, and A decrease from baseline in the modified Mayo score >= 30%, and A decrease in rectal bleeding(RB) subscore of >= 1 point or absolute RB subscore <= 1
-Endoscopic Response rate at Week 12 defined as endscopic subscore<= 1
-Endoscopic Remission rate at Week 12 defined as an endoscopic subscore of 0

+81-172-32-4311

June. 11, 2019