Ignite Creation Date:
2025-12-25 @ 3:09 AM
Ignite Modification Date:
2025-12-31 @ 9:19 PM
Study NCT ID:
NCT06663605
Status:
COMPLETED
Last Update Posted:
2025-08-07
First Post:
2024-10-25
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Phase 1 Study Evaluating PALI-2108 in Healthy Volunteers and Ulcerative Colitis Patients.
Sponsor:
Palisade Bio
Organization:
Study Overview
Official Title:
A Phase 1, Double-Blind, Placebo-Controlled, Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics Study of PALI-2108 in Healthy Volunteers and Open-Label Study of a Patient Cohort With Ulcerative Colitis
Status:
COMPLETED
Status Verified Date:
2025-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
PALI-2108 is a new oral medication designed to treat ulcerative colitis (UC) by targeting the intestines. It works as a phosphodiesterase-4 (PDE4) inhibitor prodrug, meaning it becomes active only after being processed by bacteria in the colon. This targeted approach reduces the risk of side effects that can occur with other medications that affect the entire body.
Recent studies have shown that patients with active UC, especially those with moderate to severe symptoms, have higher levels of PDE4 and related biomarkers. These biomarkers are linked to the severity of their disease, suggesting that inhibiting PDE4 could help manage UC effectively.
The goal of this Phase 1 study is to evaluate the safety, tolerability, and how the body processes (pharmacokinetics) and responds to (pharmacodynamics) PALI-2108 in healthy volunteers. Although there are already PDE4 inhibitors on the market, PALI-2108 is a completely new compound that has not been tested in humans before. The study will involve two parts: first, participants will receive single doses of the drug, and then, in the second part, they will take it twice a day for seven days.
The twice-daily dosing schedule is designed to maximize drug exposure in the colon. The investigators will also investigate how food affects the drug's absorption.
Additionally, a small group of stable UC patients will be included in the study. These patients will also take PALI-2108 for seven days, allowing us to compare the safety and drug processing between healthy individuals and those with UC. The investigators will monitor important health markers and conduct tests on colon tissue to see how well the drug works and if it causes any changes in the tissue.
Including UC patients early in this research is important for understanding how the drug performs in real-world conditions. This data will help refine our approach to identify which patients might benefit most from PALI-2108 in future studies.
Overall, this study aims to gather crucial information about PALI-2108's safety and effectiveness, paving the way for new treatment options for patients with ulcerative colitis.
Recent studies have shown that patients with active UC, especially those with moderate to severe symptoms, have higher levels of PDE4 and related biomarkers. These biomarkers are linked to the severity of their disease, suggesting that inhibiting PDE4 could help manage UC effectively.
The goal of this Phase 1 study is to evaluate the safety, tolerability, and how the body processes (pharmacokinetics) and responds to (pharmacodynamics) PALI-2108 in healthy volunteers. Although there are already PDE4 inhibitors on the market, PALI-2108 is a completely new compound that has not been tested in humans before. The study will involve two parts: first, participants will receive single doses of the drug, and then, in the second part, they will take it twice a day for seven days.
The twice-daily dosing schedule is designed to maximize drug exposure in the colon. The investigators will also investigate how food affects the drug's absorption.
Additionally, a small group of stable UC patients will be included in the study. These patients will also take PALI-2108 for seven days, allowing us to compare the safety and drug processing between healthy individuals and those with UC. The investigators will monitor important health markers and conduct tests on colon tissue to see how well the drug works and if it causes any changes in the tissue.
Including UC patients early in this research is important for understanding how the drug performs in real-world conditions. This data will help refine our approach to identify which patients might benefit most from PALI-2108 in future studies.
Overall, this study aims to gather crucial information about PALI-2108's safety and effectiveness, paving the way for new treatment options for patients with ulcerative colitis.
Detailed Description:
PALI-2108 is a novel synthetic prodrug designed to function as an intestinally activated phosphodiesterase-4 (PDE4) inhibitor, with a unique galactose sugar moiety linked by a beta 1,4 bond that enhances its targeted delivery within the colon. This innovative formulation minimizes systemic exposure and potential central nervous system (CNS) mediated toxicity by being cleaved by colonic bacterial enzyme β-glucuronidase, thus releasing the active PDE4 inhibitor directly in the colonic tissue. This mechanism is particularly advantageous in treating conditions like ulcerative colitis (UC), where localized treatment can enhance safety and efficacy.
Recent proprietary bioinformatics analyses indicate that patients with active UC, especially those with moderate to severe disease, exhibit significantly elevated levels of PDE-4 and PDE-4 related transcriptional biomarkers. These biomarkers have been found to correlate with established markers of UC disease activity and severity, such as the Mayo score. This highlights the potential role of PDE-4 inhibition in managing UC, making PALI-2108 a promising candidate for further investigation.
The primary aim of this single-center Phase 1 study is to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of PALI-2108 in healthy volunteers. Although several PDE-4 inhibitors have received market approval, but not in Ulcerative Colitis, PALI-2108 represents a new chemical entity that has not been previously administered to humans. The study will consist of single ascending dose (SAD) cohorts followed by multiple ascending dose (MAD) cohorts, with participants receiving twice-daily (BID) dosing for seven consecutive days. This BID regimen is designed to optimize colonic exposure to the active PDE4 inhibitor.
In addition to healthy volunteers, a small cohort of stable moderate to severe UC patients will be included in the study. These patients, who will be under standard care, will also receive BID dosing for seven days. Comprehensive safety monitoring and similar PK evaluations will be conducted in this cohort. Biomarkers, including high sensitivity C-reactive protein (hsCRP) and fecal calprotectin (CalPro), along with colonic tissue histological assessments, will be employed to provide further insights into the drug's effects. The analysis of colon tissue will include the study drug and metabolite levels, PDE4 expression, and related PD biomarkers, which are crucial for understanding the drug's mechanism and efficacy.
This early inclusion of UC patients is strategic, allowing for the correlation of PK/PD profiles between healthy volunteers and UC subjects. It also enables close monitoring of safety within a controlled clinical pharmacology unit. The comprehensive data gathered will support Palisade Bio's Precision Medicine Strategy, aimed at identifying patient responders for future clinical studies. Overall, the study of PALI-2108 has the potential to advance therapeutic options for UC, emphasizing localized treatment and improved patient safety.
Recent proprietary bioinformatics analyses indicate that patients with active UC, especially those with moderate to severe disease, exhibit significantly elevated levels of PDE-4 and PDE-4 related transcriptional biomarkers. These biomarkers have been found to correlate with established markers of UC disease activity and severity, such as the Mayo score. This highlights the potential role of PDE-4 inhibition in managing UC, making PALI-2108 a promising candidate for further investigation.
The primary aim of this single-center Phase 1 study is to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of PALI-2108 in healthy volunteers. Although several PDE-4 inhibitors have received market approval, but not in Ulcerative Colitis, PALI-2108 represents a new chemical entity that has not been previously administered to humans. The study will consist of single ascending dose (SAD) cohorts followed by multiple ascending dose (MAD) cohorts, with participants receiving twice-daily (BID) dosing for seven consecutive days. This BID regimen is designed to optimize colonic exposure to the active PDE4 inhibitor.
In addition to healthy volunteers, a small cohort of stable moderate to severe UC patients will be included in the study. These patients, who will be under standard care, will also receive BID dosing for seven days. Comprehensive safety monitoring and similar PK evaluations will be conducted in this cohort. Biomarkers, including high sensitivity C-reactive protein (hsCRP) and fecal calprotectin (CalPro), along with colonic tissue histological assessments, will be employed to provide further insights into the drug's effects. The analysis of colon tissue will include the study drug and metabolite levels, PDE4 expression, and related PD biomarkers, which are crucial for understanding the drug's mechanism and efficacy.
This early inclusion of UC patients is strategic, allowing for the correlation of PK/PD profiles between healthy volunteers and UC subjects. It also enables close monitoring of safety within a controlled clinical pharmacology unit. The comprehensive data gathered will support Palisade Bio's Precision Medicine Strategy, aimed at identifying patient responders for future clinical studies. Overall, the study of PALI-2108 has the potential to advance therapeutic options for UC, emphasizing localized treatment and improved patient safety.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?: