A Trial to Investigate PALI-2108 Versus Placebo in Participants With Moderately to Severely Active Ulcerative Colitis

Prior treatment

• Any prior history of suicidal behavior (actual, interrupted, aborted attempt, or preparatory acts).

Other illness

• Failure or intolerance of \> 3 classes of approved advanced therapies or \> 4 approved individual advanced therapies.

Other

• UC limited to rectum (\< 15 cm from anal verge).
• Columbia-Suicide Severity Rating Scale (C-SSRS) suicidal ideation type 4 or 5, or any active suicidal ideation with some intent to act.
• Severe depression at Screening based on a validated scale threshold (e.g., Patient Health Questionnaire-9 \[PHQ-9\] ≥ 20, or PHQ-9 item 9 \> 0) at Screening.

• Documented clinical diagnosis of UC for ≥ 3 months prior to Screening. The diagnosis of UC must be confirmed by endoscopic and histologic evidence.
  • If a histopathology report is not available in the source records, a biopsy for a local histopathology evaluation (to obtain a report) can be obtained during the screening endoscopy procedure.
• Moderately to severely active UC, defined as:
  • mMS of 5 to 9 (inclusive), AND
  • ES ≥ 2, AND
  • RB ≥ 1.
• Participants must satisfy at least one of the criteria listed under item a OR at least one of the criteria listed under item b:
  • History of inadequate response or loss of response, or intolerance to at least one prior UC therapy, defined as: i. Oral prednisone ≥ 40 mg/day (or equivalent) or budesonide ≥ 9 mg/day for ≥ 2 weeks.
• Corticosteroid dependence: unable to taper \< 10 mg/day prednisone equivalent within 3 months, or relapse within 3 months of discontinuation.
• Immunosuppressants: azathioprine ≥ 2 mg/kg/day, 6-mercaptopurine (6-MP) ≥ 1.0 mg/kg/day (or therapeutic 6-thioguanine nucleotide \[6-TGN\] level) for ≥ 12 weeks, or methotrexate ≥ 15 mg/week subcutaneous or intramuscular.
• Approved advanced therapies at the approved labelled dose:
• Anti-tumor necrosis factor (TNF), anti-integrin (vedolizumab), or anti-IL-12/23 for at least 8 weeks; anti-IL 23 for at least 12 weeks.
• Janus kinase (JAK) inhibitor for at least 8 weeks; sphingosine-1-phosphate receptor (S1PR) modulator for at least 12 weeks.
  • Note: Demonstration of intolerance requires no minimum dose nor duration of use.
• Currently receiving one or more of the following treatments: i. Stable oral prednisone at ≤ 20 mg/day (or equivalent) or budesonide ≤ 9 mg for ≥ 2 weeks prior to randomization.
• Stable dose of thiopurine (azathioprine or 6-MP) for ≥ 4 weeks prior to randomization, and have started the treatment ≥ 12 weeks prior to randomization.
• Stable dose of oral aminosalicylates for ≥ 2 weeks prior to randomization.