Safety, Tolerability, and Pharmacokinetics of Oral NX-13 in Active Ulcerative Colitis

Study Overview
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Brief Summary
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This is a Phase 1b, randomized, double-blind, multicenter dose-ranging study to evaluate the safety, tolerability, and PK of NX-13. Approximately 40 subjects will be randomized in a 3:3:3:1 ratio to receive 1 of 3 NX-13 treatment regimens (NX-13 250 mg IR, 500 mg IR, 500 mg MR) (12 evaluable subjects at each of the 3 dose levels) or placebo (4 subjects), once daily for 28 consecutive days.

Detailed Description
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Following screening period (up to 28 days in length), a total of 40 subjects are planned to be enrolled into this study from multiple sites in the United States, Australia, New Zealand, and Moldova. Eligible subjects will be randomized in a 3:3:3:1 ratio to receive 1 of 3 NX-13 treatment regimens (NX-13 250 mg IR, 500 mg IR, 500 mg MR) or placebo via a computer-generated interactive web response system (IWRS). Each of the NX-13 treatment groups will comprise 12 subjects and 4 subjects will be randomized to receive placebo. The study will include a maximum of 25% of subjects who have had prior exposure to biologic therapy for UC. Dosing will extend over a 28-day period at each dose level. Subjects will receive the first dose of study drug in clinic on Day 1 (Visit 2) and Day 28 (Visit 4/EOT) but will self-administer IP at home once daily for the remaining dosing days. The study duration will be approximately 63 days: Screening Period (28 days) + Treatment Period (28 days) + Safety Follow-up (7 days after last dose). There will be a follow-up visit on Day 35 (Visit 5).

Official Title
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A Randomized, Double-blind Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Oral NX-13 in Active Ulcerative Colitis

Conditions
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Ulcerative Colitis

Intervention / Treatment
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* Drug: NX-13 250mg IR
* Drug: NX-13 500mg IR
* Drug: NX-13 500mg MR
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: male and female subjects aged 18 to 75 years (inclusive) with a diagnosis of UC ≥ 90 days before screening; active UC defined as a total Mayo Score of 4 to 10 (inclusive), at baseline, with a Mayo endoscopic subscore (MES) ≥ 2 confirmed by a central reader; baseline fecal calprotectin ≥ 250 μg/g; biologic-naïve or having stopped biologic therapy ≥ 8 weeks before the start of the study; 5-aminosalicylates must be stable for ≥ 1 month prior to randomization. Key Exclusion Criteria: Crohn's disease (CD), indeterminate colitis, or presence or history of fistula with CD; a history of toxic megacolon, abdominal abscess, symptomatic colonic stricture, or stoma; history of or at imminent risk of colectomy; history of or current colonic dysplasia ; recent history (within 2 years prior to randomization) or current adenomatous colonic polyps; treatment with an immunosuppressant within 3 months of randomization; bacterial or parasitic pathogenic enteric infection; live virus vaccination within 1 month prior to screening.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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 |
| --- | --- |
| Experimental: NX-13 250mg IR<br>Oral | Drug: NX-13 250mg IR<br>* Subjects will take study drug by ingesting one tablet per day, recommended at the same time in the morning for consistency. Subjects in a NX-13 group will receive either 250 mg or 500 mg of NX-13 in an immediate release or modified release tablet and subjects in the placebo group will receive matched placebo.<br>|
| Experimental: NX-13 500mg IR<br>Oral | Drug: NX-13 500mg IR<br>* Subjects will take study drug by ingesting one tablet per day, recommended at the same time in the morning for consistency. Subjects in a NX-13 group will receive either 250 mg or 500 mg of NX-13 in an immediate release or modified release tablet and subjects in the placebo group will receive matched placebo.<br>|
| Experimental: NX-13 500mg MR<br>Oral | Drug: NX-13 500mg MR<br>* Subjects will take study drug by ingesting one tablet per day, recommended at the same time in the morning for consistency. Subjects in a NX-13 group will receive either 250 mg or 500 mg of NX-13 in an immediate release or modified release tablet and subjects in the placebo group will receive matched placebo.<br>|
| Placebo Comparator: Placebo<br>Oral | Drug: Placebo<br>* Subjects will take study drug by ingesting one tablet per day, recommended at the same time in the morning for consistency. Subjects in a NX-13 group will receive either 250 mg or 500 mg of NX-13 in an immediate release or modified release tablet and subjects in the placebo group will receive matched placebo.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment-Emergent Adverse Events after multiple oral dose administration of NX-13 in subjects with active ulcerative colitis (UC) | Incidence of Treatment-Emergent Adverse Events after multiple oral dose administration of NX-13 | 63 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK profile of NX-13 after multiple oral dose administration in subjects with active UC | NX-13 concentrations in plasma, colonic tissue biopsies, and feces | 63 days | 
| PK Parameters - Time to maximum concentration (tmax); | NX-13 concentrations, time to maximum concentration | 63 days | 
| PK Parameters- Maximum concentration (Cmax) | NX-13 concentrations, maximum concentration | 63 days | 
| PK Parameters- Area under the concentration-time curve from time 0 to last measurable time-point (AUC0-tlast); | NX-13 concentrations, area under the concentration-time curve from time 0 to last measurable | 63 days | 
| PK Parameters-Terminal half-life (t1/2) | NX-13 terminal half-life PK | 63 days | 
| PK Parameters- clearance (CL); | NX-13 clearance PK | 63 days | 
| PK Parameters- Vz, apparent volume of distribution during terminal phase. | NX-13 - Vz, apparent volume of distribution during terminal phase. | 63 days |