PN-943 in Adults With Moderate to Severe Active Ulcerative Colitis (UC)

Study Overview
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Brief Summary
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The purpose of the study is to evaluate the safety, tolerability, and clinical efficacy of PN-943 450 mg twice daily [BID] and PN-943 150 mg BID, compared with placebo BID, in subjects with moderate to severe active Ulcerative Colitis (UC).

Detailed Description
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The study consists of a 12-week double-blind, placebo-controlled treatment period. Participants will be randomized in a 1:1:1 ratio to PN-943 450 mg BID, PN-943 150 mg BID, or matching placebo BID. Participants who successfully complete the double-blind period may be eligible for an extended treatment period of 40 weeks duration.

Official Title
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A Phase 2 Randomized, Double-blind, Placebo-controlled, Parallel-group, Multi-center Study to Evaluate the Safety and Efficacy of Oral PN-943 in Subjects With Moderate to Severe Active Ulcerative Colitis

Conditions
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Ulcerative Colitis Chronic Moderate, Ulcerative Colitis Chronic Severe

Intervention / Treatment
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* Drug: PN-943
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Male and female subjects age 18 (or the minimum country specific age of consent if >18) to 75 years. Subject understands the study procedures and agrees to participate in the study by giving written informed consent. Diagnosis of UC supported by appropriate documentation of biopsy results consistent with UC. Moderate to severe active UC. Demonstrated inadequate response, loss of response, or intolerance of at least 1 of oral aminosalicylates (5-ASAs), corticosteroids, immunomodulators, or a biologic (excluding vedolizumab). Key Exclusion Criteria: Subject with a current diagnosis of Crohn's disease (CD), indeterminate colitis (IC), microscopic colitis, ischemic colitis, radiation colitis. History of colonic dysplasia other than completely removed low-grade dysplastic lesion. History of active bacterial, viral, fungal or mycobacterial infection requiring hospitalization or IV antibiotic/anti-infective treatment within 4 weeks of screening or oral antibiotics/anti-infectives within 2 weeks of screening. Prior treatment with vedolizumab, natalizumab, or any agent targeting the α4β7 or β1 integrin or planned during the study. Positive stool test for C. difficile. Chronic recurrent or serious infection. Known primary or secondary immunodeficiency. Pregnant or lactating female or considering becoming pregnant during the study or within 30 days after the last dose of study medication. History of any major neurological disorders.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Interventional Model Description: 12-week randomized, double-blind, placebo-controlled, parallel design study in patients with moderate to severe active UC. It will be followed by 40 weeks of Extended Active Treatment.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PN-943 450 mg BID<br>Oral administration of PN-943 450 mg BID | Drug: PN-943<br>* Administered by the oral route BID for the duration of the study.<br>|
| Experimental: PN-943 150 mg BID<br>Oral administration of PN-943 150 mg BID | Drug: PN-943<br>* Administered by the oral route BID for the duration of the study.<br>|
| Placebo Comparator: Placebo BID<br>Oral administration of matching placebo | Drug: Placebo<br>* Administered by the oral route BID for 12 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects achieving clinical remission at Week 12 compared to placebo. | Clinical remission is determined using the Adapted Mayo score (sum of 3 subscores from the Mayo score): Stool frequency subscore (SFS) Rectal bleeding subscore (RBS) Endoscopic subscore (ESS) | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison between PN-943 high-dose and low-dose individually to placebo. | Proportion of subjects with endoscopic improvement. Proportion of subjects achieving endoscopic remission. Proportion of subjects with histological improvement. Proportion of subjects achieving histological remission. Proportion of subjects with mucosal healing. | Week 12 | 

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