An Investigation of Oral BT051 in Subjects With Moderately to Severely Active Ulcerative Colitis (UC)

Phase 1

Completed

• Conditions: Ulcerative Colitis
• Interventions: Drug: BT051 800 mg; Drug: BT051 3200 mg; Drug: BT051 200 mg; Drug: Matching Placebo

• Registration Number: NCT05084261
• Lead Sponsor: Adiso Therapeutics

Brief Summary

This is a randomised, double-blind, placebo-controlled study to assess the safety and tolerability of multiple ascending doses of BT051 in subjects with moderately to severely active ulcerative colitis. Subjects will be randomised using a 3 active:1 placebo ratio to 3 ascending dose cohorts of 8 subjects and will be dosed daily for 28 days. The 3 initial dose levels will be 200 mg, 800 mg and 3200 mg per day. Progression to the next cohort will be based on the safety and tolerability of the previous cohort.

Detailed Description

This is a randomized, placebo-controlled, multiple-ascending-dose (MAD) study enrolling subjects with moderately to severely active UC. Subjects with prior exposure to biologic or JAK inhibitors will be limited to 30% of the total subject population; those who have failed 2 or more biologic therapies (i.e., biologic and JAK inhibitor, 2 biologics in the same class, or 2 biologics from different classes) will be limited to 20% of the total subject population. Subjects will be randomized to one of 3 doses of oral BT051 (200 mg, 800 mg, or 3200 mg) or placebo, in ascending dose groups based on the safety and tolerability of the previous cohort. Safety and tolerability will be assessed by a Safety Review Committee (SRC) after all subjects in each cohort have completed at least 14 days of treatment, before proceeding to the next higher dose cohort. The SRC may recommend that the next cohort proceed with a higher dose as planned, or the SRC may recommend additional subjects be dosed at the current, previous, or lower dose of study drug.

Each planned dose escalation cohort (Cohorts 1-3) will include 8 subjects randomized 3:1 to receive active drug or placebo. Starting with the lowest dose, each cohort of subjects will receive once daily oral BT051 or placebo for a period of 28 days. Follow-up visits will be performed at 7 and 30 days after the last dose.

Study Timeline

• Study First Submitted: 2021-09-20
• Study First Submitted QC: 2021-10-15
• Study First Posted: 2021-10-19
• Study Start: 2021-11-30
• Primary Completion: 2022-11-30
• Study Completion: 2022-11-30
• Status Verified: 2024-02
• Last Update Submitted: 2024-02-06
• Last Update Posted: 2024-02-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
BT051 800 mg	BT051 800 mg	Participants will receive oral BT051 800 mg once daily for 28 days.
BT051 3200 mg	BT051 3200 mg	Participants will receive oral BT051 3200 mg once daily for 28 days.
BT051 200 mg	BT051 200 mg	Participants will receive oral BT051 200 mg once daily for 28 days.
Placebo	Matching Placebo	Participants will receive oral Placebo to match BT051 once daily for 28 days.

Primary Outcome Measures

Name	Time	Method
Evaluate the safety and tolerability of BT051 based on the difference of proportions between treatment groups of subjects observed with a change from baseline in physical examinations, clinical laboratory tests, vital signs, and electrocardiograms (ECG)	Baseline to Day 58	Proportion of subjects with a change from baseline from normal to abnormal in physical examinations, clinical laboratory tests, vital signs, and ECGs will be summarized
Evaluate the safety and tolerability of BT051 based on the difference of proportions between treatment groups of subjects experiencing treatment-emergent adverse events (TEAEs)	Baseline to Day 58	Proportion of subjects experiencing a TEAE will be summarized using the MedDRA system organ class and preferred term

Secondary Outcome Measures

Name	Time	Method
Clinical response defined as a decrease in complete Mayo Score ≥2 points and ≥30% from baseline with a concomitant decrease in rectal bleeding subscore ≥1 point or absolute rectal bleeding subscore ≤1	Baseline to Day 28	Proportion of subjects who achieve clinical response defined as a decrease in complete Mayo Score ≥2 points and ≥30% from baseline with a concomitant decrease in rectal bleeding subscore ≥1 point or absolute rectal bleeding subscore ≤1 point at Day 28
Histologic remission defined as Geboes Score ≤2B.0 or Nancy Index = 0	Day 28	Proportion of subjects who achieve histologic remission (defined as Geboes Score ≤2B.0 or Nancy Index = 0) at Day 28
Change in Ulcerative Colitis Endoscopic Index of Severity (UCEIS) score	Baseline to Day 28	Difference between treatment groups of mean change in UCEIS score from baseline to Day 28.; The UCEIS consists of the following 3 descriptors and is calculated as a simple sum: erosions and ulcers (scored 0-3), bleeding (scored 0-3) and vascular pattern (scored 0-2). Calculated scores range from 0 to 8 with higher scores indicating more severe disease.
Remission defined as a complete Mayo Score ≤2 points with no subscore >1 point at Day 28	Baseline to Day 28	Proportion of subjects in clinical remission defined as a complete Mayo Score ≤2 points with no subscore \>1 point at Day 28
Remission defined as a partial Mayo Score ≤2 points with no subscore >1 point at Days 14 and 28	Baseline to Days 14 and 28	Proportion of subjects in clinical remission defined as a partial Mayo Score ≤2 points with no subscore \>1 point at Day 14 and Day 28
Endoscopic remission defined as an Ulcerative Colitis Endoscopic Index of Severity (UCEIS) score of 0	Day 28	Proportion of subjects who achieve endoscopic remission defined as an UCEIS score of 0 at Day 28
Change in Mayo endoscopic, stool frequency, and rectal bleeding subscores.	Baseline to Day 28	Proportion of subjects with a change in Mayo endoscopic, stool frequency, and rectal bleeding subscores from baseline to Day 28
Endoscopic response defined as a decrease in UCEIS ≥2 points	Day 28	Proportion of subjects who achieve endoscopic response defined as a decrease in UCEIS ≥2 points at Day 28.
Change in Robarts histopathology index (RHI) score	Baseline to Day 28	Difference between treatment groups of mean change in Robarts histopathology index (RHI) score from baseline to Day 28.; The RHI score ranges from 0 (no disease activity) to 33 (severe disease activity) based on the evaluation of 4 main parameters: chronic inflammatory infiltrate, lamina propria neutrophils and eosinophils, neutrophils in the epithelium, and erosion and ulceration.
Change in UC-100 score	Baseline to Day 28	Difference between treatment groups of mean change in UC-100 score from baseline to Day 28.; The UC-100 is a composite disease activity index consisting of clinical, endoscopic, and histological findings. The UC-100 will be calculated by adding the weighted Mayo stool frequency and endoscopy subscores, and RHI score as follows: UC-100 Score = 1 + (16 × stool frequency) + (6 × MES) + (RHI score); The total UC-100 score ranges from 1 to 100, with higher scores representing more severe disease activity.
Clinical response defined as a decrease in complete Mayo Score ≥3 points and ≥30% from baseline with a concomitant decrease in rectal bleeding subscore ≥1 point or absolute rectal bleeding subscore ≤1 point	Baseline to Day 28	Proportion of subjects who achieve clinical response defined as a decrease in complete Mayo Score ≥3 points and ≥30% from baseline with a concomitant decrease in rectal bleeding subscore ≥1 point or absolute rectal bleeding subscore ≤1 point at Day 28
Remission according to the adapted Mayo Score without the physician's global assessment, defined as a stool frequency subscore ≤1 point, rectal bleeding subscore of 0, and endoscopic subscore ≤1 point	Baseline to Day 28	Proportion of subjects in clinical remission according to the adapted Mayo Score without the physician's global assessment, defined as a stool frequency subscore ≤1 point, rectal bleeding subscore of 0, and endoscopic subscore ≤1 point
Change in stool frequency and rectal bleeding Mayo subscores	Baseline to Day 14	Proportion of subjects with a change in stool frequency and rectal bleeding Mayo subscores from baseline to Day 14

Trial Locations

Locations (6)

Inland Empire Clinical Trials, LLC; 🇺🇸 Rialto, California, United States

I.H.S. Health, LLC; 🇺🇸 Kissimmee, Florida, United States

Research Institute of Clinical Medicine Todua Clinic; 🇬🇪 Tbilisi, Georgia

Republican Clinical Hospital - Timofei Mosneaga; 🇲🇩 Chisinau, Moldova, Republic of

WIP Warsaw IBD Point; 🇵🇱 Warszawa, Poland

PlanetMed Gastroenterology; 🇵🇱 Wrocław, Poland