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

NCT07428096 | Active Not Recruiting Phase 1

• 1 other identifier: PBI-2108-101 (FSCD)
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Fibrostenotic Crohn's Disease

Keywords

Phosphodiesterase 4 Inhibitor; PDE4 Inhibition; Intestinal Fibrosis; Inflammatory Bowel Disease (IBD); Ileal Stricture; Crohn's Disease; PALI-2108; Oral PDE4 Inhibitor

Outcome Measures

Primary Outcomes (4)

• Safety and tolerability of PALI-2108 administered for 14 days.

  Adverse events in FSCD patients receiving PALI-2108

  14 days

• Safety and tolerability of PALI-2108

  Incidence of clinically significant laboratory abnormalities

  14 Days

• Safety and tolerability of PALI-2108

  Incidence of clinically significant ECG findings

  14 Days

• Safety and tolerability of PALI-2108

  Incidence of clinically significant vital signs findings

  14 Days

Secondary Outcomes (11)

• Maximum Concentration (Cmax)

  Day 1

• Concentration at 12 hours (C12)

  Day 1

• Time to Cmax (Tmax)

  Day 1

• Area under the plasma concentration-time curve (AUC0-24)

  Day 1

• Terminal half-life (t1/2)

  Day 1 and Day 13

Other Outcomes (28)

• Change in PDE-4 expression and related molecular pathways in ileal tissue.

  Baseline to Day 14.

• Change in endoscopic severity using the Simple Endoscopic Score for Crohn's Disease (SES-CD).

  Screening to Day 14 ileocolonoscopy

• Change in intestinal ultrasound (IUS) parameters of ileal strictures (inflammatory and fibrotic features).

  Baseline to Day 13

Study Arms (1)

FSCD Arm

EXPERIMENTAL

PALI-2108 All participants receive once-daily oral PALI-2108 for 14 days in the fed state. Two sentinel subjects receive a titrated regimen from 5 mg to 20 mg. After 7 days of sentinel dosing, the Safety Review Committee (SRC) reviews safety data and assigns the subsequent two patients to a target dose of 25 mg, with a predefined titration schedule. If the 25 mg dose is judged to be safe, all remaining subjects receive a target daily dose of 30 mg, also with a predefined titration scheme. Dose reductions may occur if safety profile is not judged adequate by SRC. Dosing is site-administered except on protocol-specified days when self-administration at home is permitted.

Drug: PALI-2108

Interventions

PALI-2108 DRUG

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.

FSCD Arm

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Provision of signed and dated informed consent form (ICF)
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Aged at least 18 years but not older than 60 years
• Body mass index (BMI) within 18.5 kg/m2 to 30.0 kg/m2, inclusively
• Non- or ex-smoker
• Healthy adult male or female
• Have no clinically significant (CS) diseases captured in the medical history or evidence of CS findings on the physical examination (including vital signs) and/or ECG, as determined by an Investigator
• Provision of signed and dated ICF
• Stated willingness to comply with all study procedures and availability for the duration of the study
• If male, meets one of the following criteria:
• Is able to procreate and agrees to use one of the accepted contraceptive regimens and not to donate sperm from the first study drug administration to at least 90 days after the last study drug administration. An acceptable method of contraception includes one of the following:
• Abstinence from heterosexual intercourse
• Male condom with spermicide or male condom with a vaginal spermicide Or
• Is unable to procreate; defined as surgically sterile
• If female, meets one of the following criteria:

You may not qualify if:

• Female who is lactating
• Female who is pregnant according to the pregnancy test at Screening or Day -1
• History of significant hypersensitivity to PALI-2108 or any other PDE-4 inhibitor (including excipients of the formulations) as well as severe hypersensitivity reactions (like angioedema) to any drugs
• Presence or history of significant gastrointestinal, liver or kidney disease, or surgery that may affect drug bioavailability or transit
• Presence of history of renal disease
• History of significant cardiovascular, pulmonary, hematologic, neurological, psychiatric, endocrine, immunologic, or dermatologic disease
• An active infection or a recent history of serious infections 30 days prior to first study drug administration
• Presence of CS vital sign and/or ECG abnormalities (based on the average of triplicate ECG readings) at the Screening visit, as defined by medical judgment
• Major surgery in the 4 weeks prior to the first study drug administration
• Vaccination with any live vaccine within 4 weeks prior to study drug administration
• Maintenance therapy with any drug or significant history of drug dependency or alcohol abuse (\> 3 units of alcohol per day, intake of excessive alcohol, acute or chronic)
• Any CS illness in the 28 days prior to the first study drug administration
• Use of St. John's wort in the 28 days prior to the first study drug administration
• Any history of tuberculosis
• Positive test result for alcohol and/or drugs of abuse at Screening or prior to the first study drug administration

Sponsors & Collaborators

• Palisade Bio: lead
• Altasciences Company Inc.: collaborator

Study Sites (1)

Altasciences

Montreal, Quebec, H3P3H5, Canada

Location

MeSH Terms

Conditions

Inflammatory Bowel Diseases; Crohn Disease

Condition Hierarchy (Ancestors)

Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Study Type: Interventional (Clinical Trial) Phase: 1b Allocation: Non-Randomized Intervention Model: Single Group Assignment Masking: None (Open Label) Primary Purpose: Basic Science / Mechanistic Exploration

Study Record Dates

• First Submitted: November 24, 2025
• First Posted: February 23, 2026
• Study Start: October 17, 2025
• Primary Completion: January 30, 2026
• Study Completion: March 15, 2026
• Last Updated: February 23, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)