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

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

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.

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).

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.