A Study With GB004 in Adult Subjects With Active Ulcerative Colitis (UC)

Study Overview
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Brief Summary
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A 2-part study, comprising of a 36-week placebo-controlled period (PCP) and a 24-week open-label extension (OLE) period, to assess the efficacy and safety of 2 dose regimens of GB004 when added to background UC therapy of 5-aminosalicylate (5-ASA) with or without systemic steroids.

Official Title
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A Phase 2, Randomized, Double-blind, Placebo-controlled, Multi-center Study to Evaluate GB004 in Adult Subjects With Mild-to-moderate Active Ulcerative Colitis

Conditions
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Ulcerative Colitis

Intervention / Treatment
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* Drug: GB004
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult male and female subjects aged ≥ 18 years at the time of signing the informed consent form (ICF) prior to initiation of any study specific activities/procedures. UC diagnosed at least 3 months prior to first dose of investigational product (IP) on Day 1. Currently receiving treatment for UC, on a stable dose for at least 2 weeks prior to flexible sigmoidoscopy or colonoscopy, with oral 5-ASA (eg, mesalamine, sulfasalazine) alone or with one of the following oral treatments: prednisone ≤ 20 mg/day or equivalent or beclomethasone ≤ 5 mg/day or budesonide or budesonide multi-matrix (MMX) of ≤ 9 mg/day Exclusion Criteria: Prior approved biologic therapy used for the treatment of UC. Diagnosis of Crohn's disease, indeterminate colitis, or pouchitis, or presence of bacterial or parasitic infection. Tofacitinib, oral cyclosporine, sirolimus or mycophenolate mofetil within 8 weeks of Day 1. Azathioprine, or 6-mercaptopurine within 1 day of Day 1. NOTE: Other Inclusion/Exclusion criteria may apply per protocol.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: PCP Placebo<br>PCP Placebo for oral administration for 36 weeks | Drug: Placebo<br>* oral tablet<br>|
| Experimental: PCP GB004 480 mg QD<br>PCP GB004 480 mg QD for oral administration for 36 weeks | Drug: GB004<br>* oral tablet<br>|
| Experimental: PCP GB004 480 mg BID<br>PCP GB004 480 mg BID for oral administration for 36 weeks | Drug: GB004<br>* oral tablet<br>|
| Experimental: Open-Label Extension (OLE) GB004 480 mg BID<br>OLE GB004 480 mg BID for oral administration for 24 weeks | Drug: GB004<br>* oral tablet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Clinical Remission at PCP Week 12 | Clinical remission is defined as a Modified Mayo score ≤ 2, with a rectal bleeding subscore of 0, stool frequency subscore of 0 or 1 (with a ≥ 1 point decrease from baseline), and endoscopic subscore of 0 or 1. The Modified Mayo score is an endpoint measure composed of: Stool frequency, Rectal bleeding, and Endoscopic subscores (where the Endoscopic subscore value of 1 does not include friability), each ranging from 0 to 3, that are summed to give a total score ranging from 0 to 9 points, with higher scores indicating greater severity. | At PCP Week 12 | 
| Percentage of Participants With a Treatment Emergent Adverse Event | An adverse event (AE) is any untoward medical occurrence in a participant, whether or not considered related to study treatment. Abnormal laboratory test results or other safety assessments, including those that worsened from baseline, that were considered clinically significant in the medical and scientific judgment of the investigator were to be reported as AEs. An AE was considered treatment-emergent to the OLE if it started on or after the first dose of OLE study treatment. | From first dose of OLE study treatment through OLE Week 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Clinical Response at PCP Week 12 | Clinical response is defined as a reduction in Modified Mayo score of ≥ 2 points and ≥ 35% from baseline, including a decrease in rectal bleeding subscore of ≥ 1 or absolute rectal bleeding subscore of ≤ 1. The Modified Mayo score is an endpoint measure composed of: Stool frequency, Rectal bleeding, and Endoscopic subscores (where the Endoscopic subscore value of 1 does not include friability), each ranging from 0 to 3, that are summed to give a total score ranging from 0 to 9 points, with higher scores indicating greater severity. | At PCP Week 12 | 
| Percentage of Participants With Histologic Remission at PCP Week 12 | Histologic remission is defined as Robarts Histopathology Index (RHI) ≤ 3 with lamina propria neutrophils RHI subscore = 0 and neutrophils in epithelium RHI subscore = 0. Histologic remission is evaluated among subjects with both baseline lamina propria neutrophils and neutrophils in epithelium RHI subscores > 0. The RHI is a validated instrument that measures histologic disease activity and consists of 4 subscores (chronic inflammatory infiltrate, lamina propria neutrophils, neutrophils in epithelium, and erosion or ulceration). Each subscore ranges from 0-3, with higher subscores indicating greater histologic disease activity. The RHI score is calculated as: (1 x chronic inflammatory infiltrate) + (2 x lamina propria neutrophils) + (3 x neutrophils in epithelium) + (5 x erosion or ulceration). The RHI therefore ranges from 0-33, with higher scores indicating greater histologic disease activity. | At PCP Week 12 | 
| Percentage of Participants With Endoscopic Improvement at PCP Week 12 | Endoscopic improvement is defined as an endoscopic subscore of 0 or 1. The endoscopic subscore is a component of the Modified Mayo score and is assessed on a 0-3 scale: 0 = Normal or inactive disease; 1 = Mild disease (erythema, decreased vascular pattern); 2 = Moderate disease (marked erythema, absent vascular pattern, friability, erosions); and 3 = Severe disease (spontaneous bleeding, ulceration). Higher scores indicate greater endoscopic disease severity. An endoscopic subscore of 1 does not include friability; an endoscopy with friability is assessed an endoscopic subscore of at least 2. | At PCP Week 12 | 
| Percentage of Participants With Mucosal Healing at PCP Week 12 | Mucosal healing is defined as endoscopic improvement and histologic remission. Please see Secondary Outcome Measure Descriptions above for Percentage of Participants With Endoscopic Improvement at PCP Week 12 and for Percentage of Participants With Histologic Remission at PCP Week 12 for information on the measures of endoscopic improvement and histologic remission, respectively. | At PCP Week 12 | 
| Percentage of Participants With Clinical Remission at PCP Week 36 | Clinical remission is defined as a Modified Mayo score ≤ 2, with a rectal bleeding subscore of 0, stool frequency subscore of 0 or 1 (with a ≥ 1 point decrease from baseline), and endoscopic subscore of 0 or 1. The Modified Mayo score is an endpoint measure composed of: Stool frequency, Rectal bleeding, and Endoscopic subscores (where the Endoscopic subscore value of 1 does not include friability), each ranging from 0 to 3, that are summed to give a total score ranging from 0 to 9 points, with higher scores indicating greater severity. | At PCP Week 36 | 
| Percentage of Participants With Clinical Response at PCP Week 36 | Clinical response is defined as a reduction in Modified Mayo score of ≥ 2 points and ≥ 35% from baseline, including a decrease in rectal bleeding subscore of ≥ 1 or absolute rectal bleeding subscore of ≤ 1. The Modified Mayo score is an endpoint measure composed of: Stool frequency, Rectal bleeding, and Endoscopic subscores (where the Endoscopic subscore value of 1 does not include friability), each ranging from 0 to 3, that are summed to give a total score ranging from 0 to 9 points, with higher scores indicating greater severity. | At PCP Week 36 | 
| Percentage of Participants With Histologic Remission at PCP Week 36 | Histologic remission is defined as Robarts Histopathology Index (RHI) ≤ 3 with lamina propria neutrophils RHI subscore = 0 and neutrophils in epithelium RHI subscore = 0. The RHI is a validated instrument that measures histologic disease activity and consists of 4 subscores (chronic inflammatory infiltrate, lamina propria neutrophils, neutrophils in epithelium, and erosion or ulceration). Each subscore ranges from 0-3, with higher subscores indicating greater histologic disease activity. The RHI score is calculated as: (1 x chronic inflammatory infiltrate) + (2 x lamina propria neutrophils) + (3 x neutrophils in epithelium) + (5 x erosion or ulceration). The RHI therefore ranges from 0-33, with higher scores indicating greater histologic disease activity. | At PCP Week 36 | 
| Percentage of Participants With Endoscopic Improvement at PCP Week 36 | Endoscopic improvement is defined as an endoscopic subscore of 0 or 1. The endoscopic subscore is a component of the Modified Mayo score and is assessed on a 0-3 scale: 0 = Normal or inactive disease; 1 = Mild disease (erythema, decreased vascular pattern); 2 = Moderate disease (marked erythema, absent vascular pattern, friability, erosions); and 3 = Severe disease (spontaneous bleeding, ulceration). Higher scores indicate greater endoscopic disease severity. An endoscopic subscore of 1 does not include friability; an endoscopy with friability is assessed an endoscopic subscore of at least 2. | At PCP Week 36 | 
| Percentage of Participants With Mucosal Healing at PCP Week 36 | Mucosal healing is defined as endoscopic improvement and histologic remission. Please see Secondary Outcome Measure Descriptions above for Percentage of Participants With Endoscopic Improvement at PCP Week 36 and for Percentage of Participants With Histologic Remission at PCP Week 36 for information on the measures of endoscopic improvement and histologic remission, respectively. | At PCP Week 36 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Inflammatory Bowel Disease