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

January 2, 2024 updated by: Geert D'Haens

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

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Estimated)

12

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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

    -

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Open- label ozanimod
All patients will receive open-label ozanimod
Drug: Ozanimod Oral Capsule
open label ozanimod

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Time Frame: Baseline, week 2, 6 and 10.
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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Geert D'Haens

Collaborators

Bristol-Myers Squibb

Investigators

  • Principal Investigator: Geert DHaens, AmsterdamUMC

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

March 1, 2024

Primary Completion (Estimated)

March 1, 2026

Study Completion (Estimated)

March 1, 2027

Study Registration Dates

First Submitted

December 15, 2023

First Submitted That Met QC Criteria

January 2, 2024

First Posted (Estimated)

January 3, 2024

Study Record Updates

Last Update Posted (Estimated)

January 3, 2024

Last Update Submitted That Met QC Criteria

January 2, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2024-01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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