NCT07428096

A Study of PALI-2108 in Healthy Volunteers, Patients With Ulcerative Colitis, and Patients With Fibrostenosing Crohn's Disease

A Phase 1, Double-Blind, Placebo-Controlled, Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics Study of PALI-2108 in Healthy Volunteers, With an Open-Label Study of a Patient Cohort With Ulcerative Colitis and a Phase 1b, Open-Label, Cohort in Patients With Fibrostenosing Crohn's Disease

• Status: Active Not Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 6 (estimated)
• Sponsor: Palisade Bio · Industry
• Sex: All
• Age: 18 Years – 60 Years
• Healthy volunteers: Not accepted

Summary

This is a Phase 1b, open-label, exploratory study designed to evaluate the pharmacodynamic effects of PALI-2108, a phosphodiesterase-4 (PDE4) inhibitor, in patients with fibrostenotic Crohn's disease (FSCD). The study will assess molecular, cellular, and histologic changes in intestinal tissue and peripheral blood following short-term oral administration of PALI-2108. Eligible participants with FSCD will undergo paired ileal pinch biopsies and peripheral blood collection at baseline and after 14 days of PALI-2108 treatment. The primary objective is to elucidate the mechanism of action of PALI-2108 in modulating inflammatory and fibrotic pathways relevant to FSCD pathobiology. Analyses will include single-nucleus RNA sequencing (snRNA-seq) of intestinal biopsies and single-cell RNA sequencing (scRNA-seq) of PBMCs to profile treatment-induced transcriptomic changes across immune and stromal cell populations. The FSCD cohort is part of a larger, multi-part study that also includes a completed Phase 1a first-in-human portion in healthy volunteers and an ulcerative colitis (UC) cohort evaluating clinical and biomarker responses to PALI-2108 treatment.

Detailed description

This Phase 1b exploratory study will investigate the pharmacodynamic and mechanistic effects of short-term oral administration of PALI-2108, a selective phosphodiesterase-4 (PDE4) inhibitor, in patients with fibrostenotic Crohn's disease (FSCD). The FSCD cohort builds upon the safety, tolerability, and pharmacokinetic findings from the completed Phase 1a first-in-human study and complements the ongoing ulcerative colitis (UC) cohort that assesses clinical and biomarker responses to PALI-2108 in active disease. Fibrostenotic Crohn's disease is characterized by chronic inflammation and progressive fibrosis of the intestinal wall leading to luminal narrowing, strictures, and obstructive symptoms. Current medical therapies inadequately address the fibrotic component of disease, underscoring the need for interventions targeting both immune and stromal pathways. PDE4 inhibition represents a validated anti-inflammatory approach with emerging evidence for modulation of profibrotic signaling. In this study, patients with ileal or ileocolonic FSCD will receive PALI-2108 orally once daily for 14 days. Paired ileal pinch biopsies and peripheral blood samples will be collected at baseline (Day 1) and at the end of treatment (Day 14). The primary objective is to characterize molecular and cellular changes induced by PDE4 inhibition in intestinal and immune compartments. Transcriptomic profiling will be performed using single-nucleus RNA sequencing (snRNA-seq) on intestinal biopsies and single-cell RNA sequencing (scRNA-seq) on peripheral blood mononuclear cells (PBMCs). Analyses will evaluate treatment-associated changes in gene expression, cell-type composition, and pathway activation, with a focus on immune, epithelial, fibroblast, and myofibroblast populations implicated in FSCD pathology. Secondary and exploratory endpoints will include assessment of safety, tolerability, pharmacokinetics, and biomarker correlations across tissue and blood compartments. Data from this FSCD cohort are expected to provide mechanistic insights into the biological effects of PDE4 inhibition in fibrostenotic disease and to inform dose selection, biomarker strategies, and patient segmentation for subsequent clinical development programs of PALI-2108.

Conditions

• Fibrostenotic Crohn's Disease

Interventions

Type	Name	Description
DRUG	PALI-2108	Oral PALI-2108 administered once daily for 14 days. Sentinel subjects titrate from 5 mg to 20 mg. Subsequent patients receive a target dose between 10-30 mg based on SRC review, following protocol-specified titration schedules. Dose reductions are permitted for safety. All doses are taken in the fed state. PALI-2108 is an oral, gut-activated PDE4 inhibitor prodrug designed to release its active metabolite (PALI-0008) locally via bacterial β-glucuronidase. This targeted delivery limits systemic exposure and reduces CNS-related effects associated with systemic PDE4 inhibitors, providing localized anti-inflammatory and anti-fibrotic activity in intestinal tissue.

Timeline

• Start date: 2025-10-17
• Primary completion: 2026-01-30
• Completion: 2026-03-15
• First posted: 2026-02-23
• Last updated: 2026-02-23

Locations

1 site across 1 country: Canada