PALI-2108 for Ulcerative Colitis

Overseen By Patrick Colin, BPharm, MSc, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Palisade Bio

Must be taking: Aminosalicylates, Immunomodulators, Steroids

Must not be taking: Biologics, PDE-4 inhibitors

Disqualifiers: Pregnancy, Renal disease, Cardiovascular, others

Compensation: Varies

Number of Visits: 21

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new oral medication, PALI-2108, designed to treat ulcerative colitis (UC) by acting specifically in the intestines. It targets PDE4, a substance linked to the severity of UC symptoms. The study aims to assess the drug's safety, how the body processes it, and its effectiveness. Healthy volunteers and individuals with stable moderate to severe UC may qualify if they have had UC for at least six months and are managing symptoms with current treatments. Participants will take either single or multiple doses of the drug, and researchers will compare results between healthy individuals and those with UC. As a Phase 1 trial, this research focuses on understanding the treatment's effects in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications. However, UC patients must be on stable treatment with aminosalicylates, immunomodulators, or steroids for at least 4 weeks before the study. If you are taking biologics or PDE-4 inhibitors, you must stop them 3 months before the study.

Is there any evidence suggesting that PALI-2108 is likely to be safe for humans?

Research has shown that PALI-2108 has been safe in studies so far. In earlier trials, participants experienced no serious side effects, and lab results and heart tests (EKGs) showed no issues. This indicates that the treatment is generally well-tolerated. It's important to note that PALI-2108 is a new drug and has not been tested in humans beyond these early safety studies. However, the absence of serious side effects in initial research is encouraging for those considering joining the trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for ulcerative colitis?

Unlike the standard treatments for ulcerative colitis, which often include anti-inflammatory drugs like mesalamine or immunosuppressants such as azathioprine, PALI-2108 is unique because it potentially offers a new mechanism of action. Researchers are excited because PALI-2108 is administered orally and targets the disease in a way that may reduce inflammation more effectively and with fewer side effects. This treatment approach could lead to better management of symptoms and improved quality of life for patients with ulcerative colitis.

What evidence suggests that PALI-2108 might be an effective treatment for ulcerative colitis?

Research has shown that PALI-2108, which participants in this trial may receive, reduced colitis symptoms in animal studies, suggesting it might also help people with ulcerative colitis. This treatment targets the colon by blocking an enzyme called phosphodiesterase-4 (PDE4), linked to inflammation. By blocking this enzyme, the treatment can help manage symptoms. While other PDE4 inhibitors have shown promise, PALI-2108's focus on the colon may lead to fewer side effects than treatments affecting the whole body. Early safety studies in humans did not show any serious side effects, which is encouraging for its potential use in treating ulcerative colitis. ^{1 2 6 7 8}

Who Is on the Research Team?

Mitchell L Jones, MD, PhD

Principal Investigator

Palisade Bio

Are You a Good Fit for This Trial?

This trial is for healthy volunteers and stable ulcerative colitis (UC) patients. Participants should be adults who can take oral medication. The study excludes individuals with other significant health issues, those on certain medications that might interfere with the trial, or anyone unable to comply with study requirements.

Inclusion Criteria

Body mass index (BMI) within 18.5 kg/m2 to 30.0 kg/m2

I am a healthy adult with no significant health issues.

I have moderate to severe ulcerative colitis that is stable and well-controlled with current treatment.

Exclusion Criteria

History of significant hypersensitivity to PALI-2108 or any other PDE4 inhibitor

I have a history of kidney disease.

I do not have an active infection or a recent history of serious infections.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Single Ascending Dose (SAD)

Healthy volunteers receive single ascending doses of PALI-2108 to evaluate safety and pharmacokinetics

1 week

Daily visits for 7 days

Multiple Ascending Dose (MAD)

Healthy volunteers receive multiple ascending doses of PALI-2108 twice daily for seven days to assess safety and pharmacokinetics

1 week

Daily visits for 7 days

Ulcerative Colitis Patient Cohort

Stable UC patients receive PALI-2108 twice daily for seven days to compare safety and pharmacokinetics with healthy volunteers

1 week

Daily visits for 7 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• PALI-2108

Trial Overview PALI-2108, a new oral drug targeting UC by becoming active in the colon, is being tested for safety and how it's processed by the body. Healthy participants will first receive single doses; then they'll take it twice daily for a week. A small group of UC patients will do the same to compare results.

How Is the Trial Designed?

Group I: PALI-2108 Experimental Treatment 1 Intervention

Part A - Single Ascending oral doses of PALI-2108 in healthy adult subjects. Part B - Single oral dose crossover of PALI-2108 in healthy adult subjects. Part C - Multiple Ascending oral Doses of PALI-2108 in healthy adult subjects. Part D - (open-label) Multiple oral Doses of PALI-2108 in Ulcerative Colitis patients.

Group II: PALI-2108 Placebo Placebo Group 1 Intervention

Part A - Single Ascending oral Dose of matching placebo in healthy adult subjects. Part B - Single Ascending oral Dose of matching placebo crossover of PALI-2108 in healthy adult subjects. Part C - Multiple Ascending oral Doses of matching placebo in healthy adult subjects. Part D - (open-label) Multiple Ascending oral Doses of matching placebo in Ulcerative Colitis patients.

Who Is Running the Clinical Trial?

Palisade Bio

Lead Sponsor

Trials

3

Recruited

230+

Altasciences Company Inc.

Industry Sponsor

Trials

18

Recruited

860+

Published Research Related to This Trial

In a study of 34 cancer patients who previously experienced nausea and vomiting from low emetogenic chemotherapy, intravenous palonosetron effectively prevented chemotherapy-induced nausea and vomiting, achieving complete response rates of 88.2% in the acute phase and 67.6% in the delayed phase.

Palonosetron was well tolerated, with only two patients reporting treatment-related adverse events, indicating a favorable safety profile for this medication in managing CINV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of palonosetron as salvage treatment in the prevention of chemotherapy-induced nausea and vomiting in patients receiving low emetogenic chemotherapy (LEC). Hesketh, PJ., Morrow, G., Komorowski, AW., et al.[2022]

In a study involving 60 pediatric patients in Japan, palonosetron was found to be effective in preventing chemotherapy-induced nausea and vomiting, achieving a complete response rate of 58.6%, which exceeded the primary endpoint threshold of 30%.

The treatment was well-tolerated, with only 3.4% of patients experiencing treatment-related adverse events, and the pharmacokinetics of palonosetron were consistent across different age groups, supporting the use of a 20 μg/kg dose for all pediatric patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase III study of palonosetron for prevention of chemotherapy-induced nausea and vomiting in pediatric patients. Hara, J., Kosaka, Y., Koh, K., et al.[2021]

In a study involving 68 chemotherapy-naive patients with breast cancer or colorectal cancer, the combination of palonosetron and dexamethasone resulted in a complete response (no vomiting and no need for rescue medication) in 67.6% of participants over a 5-day period.

The treatment was well tolerated and effectively controlled chemotherapy-induced nausea and vomiting (CINV) during both the acute and delayed phases, with a complete response rate of 75% in each cancer group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-dose palonosetron and dexamethasone in preventing nausea and vomiting induced by moderately emetogenic chemotherapy in breast and colorectal cancer patients. Brugnatelli, S., Gattoni, E., Grasso, D., et al.[2022]

In a study of 134 patients with acute myeloid leukemia, the combination of palonosetron and aprepitant was found to significantly reduce nausea compared to palonosetron alone, with 43% of patients experiencing no nausea versus 27% in the single-drug group.

While the overall complete response rates for preventing vomiting were similar between the two treatments (72% vs 69%), the combination therapy also showed a longer time to anti-emetic treatment failure, indicating better overall control of chemotherapy-induced nausea and vomiting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Every-other-day palonosetron plus aprepitant for prevention of emesis following induction chemotherapy for acute myeloid leukemia: A randomized, controlled study from the "Rete Ematologica Pugliese". Di Renzo, N., Melillo, L., Porretto, F., et al.[2021]

Aprepitant, when used with standard anti-nausea medications, was well tolerated and effective in preventing chemotherapy-induced nausea and vomiting (CINV) in patients with colorectal cancer receiving moderately emetogenic chemotherapy, based on a multicenter phase II study.

The study found no significant differences in complete response rates or secondary outcomes between the aprepitant group and the standard treatment group, indicating that aprepitant is a viable option without compromising efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II, randomized study of aprepitant in the prevention of chemotherapy-induced nausea and vomiting associated with moderately emetogenic chemotherapies in colorectal cancer patients. Aridome, K., Mori, SI., Baba, K., et al.[2020]

Citations

1. palisadebio.com palisadebio.com/palisade-bio-reports-positive-pali-2108-phase-1b-clinical-data/

Palisade Bio Reports Positive PALI-2108 Phase 1b Clinical ... Sep 17, 2025. PALI-2108 demonstrated favorable safety, with no serious adverse events, lab abnormalities, or EKG concerns. Phase 1b data ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06663605

NCT06663605 | Phase 1 Study Evaluating PALI-2108 in ... 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 ...

3. gastrojournal.org gastrojournal.org/article/S0016-5085(25)00160-X/fulltext

PALI-2108, A COLON SPECIFC PDE4B INHIBITOR ... Here we demonstrated the effectiveness of PALI-2108 in reducing colitis symptoms in this standard colitis mouse model. Better-tolerated oral PDE4 inhibitors ...

4. finance.yahoo.com finance.yahoo.com/news/palisade-bio-reports-positive-pali-130000360.html

Palisade Bio Reports Positive PALI-2108 Phase 1b Clinical ... PALI-2108 demonstrated favorable safety, with no serious adverse events, lab abnormalities, or EKG concerns Phase 1b data demonstrated 100% ...

5. biospace.com biospace.com/press-releases/palisade-bio-reports-positive-phase-1a-results-for-pali-2108-a-first-in-class-terminal-ileum-and-colon-targeted-pde4-b-d-inhibitor-for-fibrostenotic-crohns-disease-and-ulcerative-colitis

Palisade Bio Reports Positive Phase 1a Results for PALI- ... Study met its primary endpoints of safety, tolerability, and pharmacokinetics (PK). No serious adverse events (SAEs) or treatment-emergent ...

6. clinicaltrialsarena.com clinicaltrialsarena.com/news/palisade-ulcerative-colitis-study/

Palisade reports outcomes from Phase Ib ulcerative colitis ... Outcomes from the Phase Ib cohort included a mean decrease of 62.8% in the modified Mayo score, with one subject achieving clinical remission.

7. firstwordpharma.com firstwordpharma.com/story/5966473

Palisade Bio Reports Positive Phase 1a Results for PALI- ... Study met its primary endpoints of safety, tolerability, and pharmacokinetics (PK) No serious adverse events (SAEs) or treatment-emergent ...

8. biospace.com biospace.com/press-releases/palisade-bio-presents-positive-preclinical-data-of-pali-2108-for-the-treatment-of-ulcerative-colitis

Palisade Bio Presents Positive Preclinical Data of PALI ... PALI-2108 reduced colitis symptoms in mice without causing CNS toxicity, suggesting it could be a novel treatment for UC. It effectively ...