Ulcerative ColitisPhase 4ULTRAZNCT06188637
Ulcerative Colitis Leukocyte TRAfficking After Treatment With Zeposia: the ULTRAZ Study
A Phase 4 study testing Ozanimod Oral Capsule in people with Ulcerative Colitis, run by Geert D'Haens.
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. Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Ulcerative Colitis
- What is being tested?
- Ozanimod Oral Capsule
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 1 Aug 2024to 1 Mar 2027
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or non-pregnant, non-lactating female patients 18 years or older.
- Documented diagnosis of UC.
- Active symptomatic UC with endoscopic Mayo score 2-3.
- Intention to start treatment with ozanimod.
- Written informed consent.
- Willing to utilize treatment as prescribed and undergo the procedures that our explained in detail in the informed consent form (ICF).
Who cannot join
- 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.
- Currently participating, or planning to participate in a study involving an investigational product.
- 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.
- Current gastro-intestinal infection (e.g. C. Diff or other pathogens).
- Active or planned pregnancy in the year following inclusion.
- Prior diagnosis of dysplasia in the colon (excluding dysplasia in resected adenomas).
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- History of malignancy in the 5 years prior to randomization except for non-melanoma skin cancer.
- Abnormal liver function tests and/or abnormal ECG that precludes S1P receptor blocker treatment as per Summary of product characteristics (SmPC).
- Previous treatment with Vedolizumab (Entyvio).
- Use of prohibited medication as listed in the SmPC
- -
About this study
Official title: 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.
Read the 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.
- Conditions
- Ulcerative Colitis
- Being tested
- Ozanimod Oral Capsule
- Medical subject headings
- Colitis, Ulcerative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ozanimod Oral CapsuleDrug
open label ozanimod
| Study group | Role | What they receive |
|---|---|---|
| Open- label ozanimod | Experimental | All patients will receive open-label ozanimod Receives: Drug: Ozanimod Oral Capsule |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline, week 2, 6 and 10.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jan 2024
- Study start1 Aug 2024 (estimated)
- Primary completion1 Mar 2026 (estimated)
- Study completion1 Mar 2027 (estimated)
Why it stopped: Funder decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Ulcerative ColitisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- This is a 2-center prospective open-label study with an 11 week follow-up period and extra disease activity check at week 26.
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Geert D'Haens
- Sponsor type
- University, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Responsible party
- Sponsor-investigator, Geert D'Haens, Amsterdam University Medical Centers (UMC), Location Academic Medical Center (AMC)
- Investigators
- Geert DHaens, Principal investigator, AmsterdamUMC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06188637
- Sponsor's protocol ID
- 2023-505382-88-00
- Other IDs
- 2023
- Acronym
- ULTRAZ
- Status last verified
- Sep 2024
- First submitted
- 15 Dec 2023
- Last updated
- 19 Sep 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective Cell Migration Study in Ulcerative Colitis Patients Treated With Ozanimod (S1P Receptor Antagonist)
- ClinicalTrials.gov ID
- NCT06188637
- Acronym / sponsor ID
- ULTRAZ / 2023-505382-88-00
- Conditions
- Ulcerative Colitis
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Funder decision
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Geert D'HaensUniversity, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Study start
- 1 Aug 2024 (estimated)
- Primary completion
- 1 Mar 2026 (estimated)
- Study completion
- 1 Mar 2027 (estimated)
- First posted
- 3 Jan 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- This is a 2-center prospective open-label study with an 11 week follow-up period and extra disease activity check at week 26.
| Arm | Type | Receives |
|---|---|---|
| Open- label ozanimod | Experimental | Drug: Ozanimod Oral CapsuleAll patients will receive open-label ozanimod |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Male or non-pregnant, non-lactating female patients 18 years or older.
- Documented diagnosis of UC.
- Active symptomatic UC with endoscopic Mayo score 2-3.
- Intention to start treatment with ozanimod.
- Written informed consent.
Key exclusion criteria (11 listed)
- 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.
- Currently participating, or planning to participate in a study involving an investigational product.
- 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.
- Current gastro-intestinal infection (e.g. C. Diff or other pathogens).
- Active or planned pregnancy in the year following inclusion.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ozanimod Oral Capsuleopen label ozanimod | Drug | Open- label ozanimod |
Primary outcome
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.
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Geert DHaens principal investigator
AmsterdamUMC
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Ozanimod Oral Capsule in people with Ulcerative Colitis, run by Geert D'Haens.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 19 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Sep 2024.