VTX002 Versus Placebo for the Treatment of Moderately to Severely Active Ulcerative Colitis

Study Overview
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Brief Summary
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This is a study to understand if taking VTX002 daily as a tablet orally is safe and effective in participants diagnosed with moderate to severe ulcerative colitis (UC). Approximately 189 participants will take VTX002 Dose A, VTX002 Dose B, or matching placebo, once daily. The study consists of a 28-day Screening Period (to see if a participant qualifies for the study), a 13-week double-blind period (a participant receives either active Dose A, Dose B or Placebo), a Long-Term Extension (LTE) Treatment Period of up to 39 weeks, an Open-Label Extension (OLE) Treatment Period of up to 143 weeks, and a 2-week Follow-Up Period. The maximal duration of treatment including the Induction Period, LTE and OLE will be 36 months.

Detailed Description
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This is a multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of VTX002 in subjects with moderately to severely active UC following daily oral administration of VTX002 as a tablet. Approximately 189 eligible subjects will be randomized in a 1:1:1 ratio to receive VTX002 Dose A, VTX002 Dose B, or matching placebo, once daily (approximately 63 subjects per treatment group). The study consists of a 28-day Screening Period, a 13-week double-blind Induction Treatment Period (including 7 days of titration followed by 12 weeks of treatment at the assigned dose), a Long-Term Extension (LTE) Treatment Period of up to 39 weeks, an Open-Label Extension (OLE) Treatment Period of up to 143 weeks, and a 2-week Follow-Up Period. The maximal duration of treatment including the Induction Period, LTE and OLE will be 36 months. Objectives Primary Objective • Assess the efficacy of VTX002 when administered for 13 weeks on clinical remission Secondary Objectives Assess the efficacy of VTX002 when administered for 13 weeks on endoscopic changes, symptomatic response and remission, histology, and mucosal healing Assess the safety and tolerability of VTX002 Assess the pharmacokinetics (PK) of VTX002 Long-Term and Open-Label Extension Objectives Assess the efficacy of VTX002 through the LTE and OLE Treatment Periods on endoscopic changes, symptomatic response and remission, histology, and mucosal healing Assess the safety of VTX002 through the LTE and OLE Treatment Periods

Official Title
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A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Clinical Efficacy and Safety of VTX002 in Subjects With Moderately to Severely Active Ulcerative Colitis

Conditions
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Colitis, Ulcerative

Intervention / Treatment
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* Drug: VTX002
* Drug: VTX002
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed with UC ≥ 3 months prior to Screening. Active UC confirmed by endoscopy Exclusion Criteria: Severe extensive colitis Diagnosis of Crohn's disease (CD) or indeterminate colitis or the presence or history of a fistula consistent with CD Diagnosis of microscopic colitis, ischemic colitis, or infectious colitis

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VTX002 Dose A<br>VTX002 Dose A tablet administered orally once daily | Drug: VTX002<br>* Dose A tablet administered orally once daily<br>* Other names: OPL-002;|
| Experimental: VTX002 Dose B<br>VTX002 Dose B tablet administered orally once daily | Drug: VTX002<br>* Dose B Tablet administered orally once daily<br>* Other names: OPL-002;|
| Placebo Comparator: Placebo<br>Placebo tablet administered orally once daily | Drug: Placebo<br>* Placebo Tablet for VTX002 administered orally once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical remission at 13 weeks | The proportion of subjects with clinical remission at Week 13 using modified Mayo score (MMS) defined as stool frequency (SF) subscore = 0 or 1, rectal bleeding (RB) subscore = 0, and endoscopic subscore (ES) ≤ 1 (excluding friability) | Day 1 of Induction treatment period to week 13 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Endoscopic improvement at Week 13 | The proportion of subjects with endoscopic improvement at Week 13 ES ≤ 1 (excluding friability) | Day 1 of Induction Treatment Period to week 13 | 
| Symptomatic remission at Week 13 | The proportion of subjects with symptomatic remission at Week 13 as defined as SF subscore = 0 or 1 and RB subscore = 0 | Day 1 of Induction Treatment Period to week 13 | 
| Histologic remission at Week 13 | The proportion of subjects with histologic remission at Week 13 as defined as Geboes Index score < 2.0. Histology will also be assessed by the Robarts Histopathology Index and Nancy Index | Day 1 of Induction Treatment Period to week 13 | 
| Endoscopic improvement-histologic remission at Week 13 | The proportion of subjects with mucosal healing at Week 13 as defined as ES ≤ 1 (excluding friability) and histologic remission measured by a Geboes Index score < 2.0 | Day 1 of Induction Treatment Period to week 13 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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moderate or severe ulcerative colitis, S1P; sphingosine 1 phosphate receptor;, Ventyx; Oppilan;