Ulcerative Colitis Leukocyte TRAfficking After Treatment With Zeposia: the ULTRAZ Study

Ulcerative Colitis Clinical Trial

— ULTRAZ  

Official title:

A Prospective Cell Migration Study in Ulcerative Colitis Patients Treated With Ozanimod (S1P Receptor Antagonist)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06188637
• Other study ID #: 2024-01
• Status: Not yet recruiting
• Phase: Phase 4
• Start date: March 1, 2024
• Est. completion date: March 1, 2027

Study information

• Verified date: January 2024
• Source: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Contact: Geert DHaens
• Phone: 0031(0)204440613
• Email: g.dhaens[@]amsterdamumc.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The ULTRAZ study is designed to better understand the mode of action of S1P receptor modulators. The alteration of leukocyte trafficking due to S1P receptors such as ozanimod is mainly investigated in rodent studies. Several previous studies show a reduced total leukocyte count in peripheral blood and only two study reported the effect of leukocyte subgroups before and after treatment with ozanimod. The change in leukocyte subgroups in peripheral blood as well as colonic mucosa and lymph nodes have not been investigated to our knowledge. Therefore, the aim of this study is to explore the changes in these three compartments.

Description:

Ozanimod is a sphingosine-1-phosphate (S1P) receptor modulator, which binds with high affinity to receptor subtypes 1 (S1P1) and 5 (S1P5). Many cell types express S1P1, including vascular endothelial cells, brain cells, and leukocytes. Normally, S1P levels are high in blood, heterogeneous in peripheral lymphoid organs (e.g. lymph nodes and Peyer's patches) and low in tissue, creating a gradient. This gradient results in direct trafficking of leukocytes out of the lymph node and into the circulation. In inflamed tissue, increased levels of S1P have been observed, leading to more leukocyte trafficking to this area. The modulation of the S1P1 receptor by ozanimod causes internalization and desensitization of S1P1 in leukocytes, reducing their migration in response to an increased S1P gradient. Therefore, leukocytes are retained in peripheral lymphoid organs. Previous studies showed a significant - and reversible - reduction of circulating leukocytes in the peripheral blood after treatment with ozanimod, but did not investigate the changes of leukocyte subtypes in colon mucosa and lymphatic system (ie peripheral lymph nodes. Not all patients respond to treatment with ozanimod. This non-response may be due to a mechanistic failure, where there is ongoing inflammation despite adequate drug concentrations caused by pharmacodynamic failure. The changes in leukocyte subtypes which this study investigates, could give more insight into this type of failure.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 12
• Est. completion date: March 1, 2027
• Est. primary completion date: March 1, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

Inclusion Criteria:

1. Male or non-pregnant, non-lactating female patients 18 years or older.

2. Documented diagnosis of UC.

3. Active symptomatic UC with endoscopic Mayo score 2-3.

4. Intention to start treatment with ozanimod.

5. Written informed consent.

6. Willing to utilize treatment as prescribed and undergo the procedures that our explained in detail in the informed consent form (ICF).

Exclusion Criteria:

1. Any conditions (e.g., history of alcohol or substance abuse, or lack of compliance) which, in the opinion of the investigator, may interfere with the patient's ability to comply with study procedures.

2. Currently participating, or planning to participate in a study involving an investigational product.

3. Current diagnosis of untreated active tuberculosis, active/chronic hepatitis B. Patients with latent tuberculosis can participate after at least 4 weeks of tuberculostatic treatment per local guidelines.

4. Current gastro-intestinal infection (e.g. C. Diff or other pathogens).

5. Active or planned pregnancy in the year following inclusion.

6. Prior diagnosis of dysplasia in the colon (excluding dysplasia in resected adenomas).

7. History of malignancy in the 5 years prior to randomization except for non-melanoma skin cancer.

8. Abnormal liver function tests and/or abnormal ECG that precludes S1P receptor blocker treatment as per Summary of product characteristics (SmPC).

9. Previous treatment with Vedolizumab (Entyvio).

10. Use of prohibited medication as listed in the SmPC -

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Ulcer
• Ulcerative Colitis

Intervention

Drug:
• Ozanimod Oral Capsule
open label ozanimod

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Geert D'Haens	Bristol-Myers Squibb

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To investigate changes in inflammatory cell subpopulations in the colonic mucosa, the inguinal lymph nodes, and peripheral blood in response to ozanimod induction therapy in patients ulceratie colitis.	To measure the concentration of neutrophils, lymphocytes, monocytes, and dendritic cells at week 0, 2,6 and 10 in the colonic mucosa, the inguinal lymph nodes and peripheral blood using the technique of single cell transcriptomics, spatial transcriptomics and cytometry by time of flight ( CyTOF) in response to ozanimod induction therapy in patients with moderate-to-severe ulcerative colitis.	Baseline, week 2, 6 and 10.