Immune Checkpoint Inhibitor-Related Diarrhea and ColitisPhase 2NCT06521762
Etrasimod for Immune Checkpoint Inhibitor Diarrhea and Colitis
A Phase 2 study testing Etrasimod and Corticosteroids in people with Immune Checkpoint Inhibitor-Related Diarrhea and Colitis, run by Yale University at 1 site in United States.
Trial summary
This is a randomized, double-blind, placebo-controlled, two-arm phase 2 study of etrasimod plus corticosteroids versus placebo plus corticosteroids for the treatment of IMDC CTCAE v5.0 grade ≥ 2 due to ICI therapy alone (α-PD-(L)1 monotherapy or combined with another ICI, such as α-CTLA-4 or α-LAG-3) or ICI plus an… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Immune Checkpoint Inhibitor-Related Diarrhea and Colitis
- What is being tested?
- Etrasimod and Corticosteroids
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2026to Jan 2029
- Phase
- Phase 2
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Locally advanced unresectable or metastatic cancer
- Any tumor type being treated with either α-PD-(L)1 monotherapy or combination therapy containing α-PD-(L)1 and another ICI such as α-CTLA-4 or α-LAG-3 therapy.
- Patients receiving ICI(s) in combination with oral tyrosine kinase inhibitors (TKIs) may be enrolled if their diarrhea persists despite holding the TKI for 5 days and they meet the other eligibility criteria. These cases should be discussed with one of the study PIs. Patients receiving chemotherapy in combination with ICI(s) cannot be enrolled.
- Grade ≥ 2 IMDC requiring immunosuppression with corticosteroids as defined by at least grade 2 diarrhea and grade 2 colitis by CTCAE v5.0, which are defined in Appendix 3 (section 11.3) of the protocol.
- Positive stool calprotectin test
- Able to provide informed consent.
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- Able and willing to take the study medication and comply with all study requirements.
- The following medical criteria are met:
- No known history of inflammatory bowel disease
- Vital signs at screening: pulse rate ≥ 50 beats per minute, systolic blood pressure ≥ 90 mm Hg, and diastolic blood pressure ≥ 55 mm Hg
- 12-lead electrocardiogram (ECG) that showed no clinically significant abnormalities as defined by the clinician's judgement at the time the ECG was performed
- Healthcare professional-confirmed history of varicella or a full course of vaccination against varicella zoster virus (VZV) or a positive antibody test to VZV
- Eligible patients that were biologically female at birth must be:
- Non-pregnant, as determined by qualitative urine hCG testing
- Non-lactating
- If premenopausal, be either surgically infertile OR using 2 acceptable methods of birth control for 30 days after the last dose of etrasimod is administered (inquire for a list of birth control methods considered acceptable)
Who cannot join
- Patients receiving ICIs in the adjuvant setting.
- Patients with severe hepatic impairment, as indicated by having a Child-Pugh C score.
- The following infectious complications:
- difficile infection, or an intestinal bacterial or parasitic infection detected by a multiplexed stool infection assay
- Have received treatment for C. difficile infection within 30 days or another intestinal pathogen within 30 days prior to enrollment
- Have a known history of active or latent tuberculosis, or active hepatitis B or hepatitis C
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- Have a known history of congenital or acquired immunodeficiency, including but not limited to common variable immune deficiency (CVID) and human immunodeficiency virus (HIV) infection
- Have evidence of abdominal abscess or toxic megacolon at the initial screening visit
- Patients with diabetes mellitus that meet the following criteria:
- Type 1 diabetes mellitus
- Uncontrolled type 2 diabetes mellitus requiring insulin for routine management
- Have a history of severe respiratory disease (i.e., pulmonary fibrosis, asthma, and chronic obstructive pulmonary disease) requiring supplemental oxygen not related to an underlying malignancy
- Have the following cardiovascular history:
- In the last 6 months, experienced myocardial infarction, unstable angina pectoris, stroke, transient ischemic attack, decompensated heart failure requiring hospitalization, or Class III or IV heart failure.
- Unstable ischemic heart disease, Class I or II heart failure, history of cardiac arrest, cerebrovascular disease, or uncontrolled hypertension, unless consulting cardiologist believes safe
- History or presence of Mobitz type I or II second-degree, or third-degree atrioventricular (AV) block, sick sinus syndrome, or sino-atrial block, unless the patient has a functioning pacemaker.
- A history or presence of recurrent symptomatic bradycardia or recurrent cardiogenic syncope, or severe untreated sleep apnea
- QTcF interval ≥ 450 ms in men or ≥ 470 ms in women
- Arrhythmias requiring treatment with Class Ia or Class III anti-arrhythmic drugs or QT prolonging drugs, unless consulting cardiologist believes safe
- Have received treatment that could be considered secondary IMDC treatment within 4 half-lives of the agent, including but not limited to vedolizumab, anti-TNFα antibodies, and mycophenolate mofetil. Treatments that could be considered secondary IMDC treatment but are not specified in this protocol will be adjudicated by a study PI or co-PI at the time of screening.
- Have a known history of macular edema
- Have a history of any clinically significant medical condition that, in the investigator's opinion, precludes participation in the study
- History of an opportunistic infection (e.g., Pneumocystis jirovecii, cryptococcal meningitis, progressive multifocal leukoencephalopathy) or history of disseminated herpes simplex or disseminated herpes zoster.
- Have an absolute neutrophil count (ANC) or absolute lymphocyte count (ALC) < 500
- Have received any investigational therapy, excluded medications (Appendix 4, section 11.4), or any approved therapy in an investigational protocol within 14 days before screening.
- Have active psychiatric problems that, in the investigator's opinion, could interfere with compliance with the study procedures.
- Have been using moderate to strong inhibitors of cytochrome P450 (CYP)2C9.
- Unable to discontinue any of the drugs listed in Appendix 4 (section 11.4) of the protocol
Trial locations and contacts
1 site in 1 country.
About this study
This is a randomized, double-blind, placebo-controlled, two-arm phase 2 study of etrasimod plus corticosteroids versus placebo plus corticosteroids for the treatment of IMDC CTCAE v5.0 grade ≥ 2 due to ICI therapy alone (α-PD-(L)1 monotherapy or combined with another ICI, such as α-CTLA-4 or α-LAG-3) or ICI plus an oral tyrosine kinase inhibitor that in the opinion of the treating physician requires treatment with corticosteroid-based immunosuppression and does not require immediate secondary immune suppression, such as vedolizumab or infliximab (or equivalent).
IMDC is one of the most common Immune Related Adverse Events (irAEs) from treatment with ICI. Current guidelines recommend steroid treatment for IMDC CTCAE grade ≥ 2, which requires temporary or permanent cessation of ICI therapy. Corticosteroids may interfere with the anti-tumor activity of ICIs and are therefore not co-administered. Strategies are needed to both reduce the dose and duration of corticosteroids needed for IMDC treatment and minimize the duration off ICI therapy before re-administering ICI (for those patients in whom it is deemed safe to rechallenge).
Read the detailed description
Participants will be screened as soon as IMDC is suspected but will not be randomized and administered the first dose of etrasimod or placebo until results from Clostridium difficile (C. difficile) and other intestinal infection assays are confirmed to be negative and stool calprotectin confirmed to be positive. If intestinal infectious studies are positive the participant will be excluded from the study. Due to the acute nature of some cases of IMDC (e.g., grade 4 IMDC), some participants may require initiation of corticosteroids before enrollment. In these cases, participants may be enrolled if the first dose of etrasimod or placebo can be administered within 96 hours of the first dose of corticosteroids. Participants will undergo flexible sigmoidoscopy or colonoscopy with colon biopsy prior to, within the first 7 days of starting study drug, which will be repeated 7 to 14 days after completing the last dose of study drug.
- Being tested
- Etrasimod, Placebo, Corticosteroids
- Medical subject headings
- Colitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EtrasimodDrug
Also called VELSIPITY
2 mg/day oral tablet
PlaceboDrug
matching placebo oral tablet
CorticosteroidsDrug
Corticosteroids will be given in conjunction with study drug or placebo
| Study group | Role | What they receive |
|---|---|---|
| Etrasimod plus corticosteroids | Experimental | Participants will receive Etrasimod plus corticosteroids, to be given up to 120 days, to treat IMDC. Receives: Drug: Etrasimod; Drug: Corticosteroids |
| Placebo plus corticosteroids | Placebo comparator | Participants will receive Placebo plus corticosteroids, to be given up to 120 days, to treat IMDC. Receives: Drug: Placebo; Drug: Corticosteroids |
What is being measured
The primary outcome is the main question the study is designed to answer.
Average daily weight-adjusted dose of corticosteroids use
Average daily weight-adjusted dose of corticosteroids use (up to day 120 or when a censoring event occurs), accounting for both the weight-adjusted cumulative dose of steroids and the length of treatment.
Measured: up to day 120 or when a censoring event occurs
Secondary outcomes (6)
Requirement for secondary immunosuppression
Requirement for secondary immunosuppression throughout the study period (up to day 120 or when a censoring event occurs), a binary variable (Yes or No). Numbers of participants that answered Yes/No.
Measured: up to day 120 or when a censoring event occurs
Mean time to improvement
Mean time to first improvement to CTCAE v5.0 grade ≤ 1 for IMDC in days
Measured: up to day 120 or when a censoring event occurs
Mean number of days without corticosteroids use
Mean number of days without corticosteroids use
Measured: up to day 120 or when a censoring event occurs
Safety and Tolerability Measured by Assessing Incidence and severity of adverse events of special interest.
Incidence and severity of adverse events of special interest. Number of participants that experience any adverse event of special interest determined by CTCAE v5.0.
Measured: up to day 120 or when a censoring event occurs
Incidence and severity of laboratory abnormalities
Incidence and severity of laboratory abnormalities. Total count of clinically significant abnormal labs, determined by CTCAE
Measured: up to day 120 or when a censoring event occurs
Total count of clinically significant vital sign abnormalities
Count of clinically significant vital sign abnormalities
Measured: up to day 120 or when a censoring event occurs
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jul 2024
- Study startJan 2026 (estimated)
- Primary completionJan 2029 (estimated)
- Study completionJan 2029 (estimated)
Why it stopped: The study was terminated early as no patients were enrolled.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Immune Checkpoint Inhibitor-Related Diarrhea and ColitisStudies of the same condition, open and under way.
- More trials run by Yale UniversityThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Collaborators
- Pfizer
- Responsible party
- Principal investigator, Harriet Kluger, Yale University
- Investigators
- Harriet Kluger, MD, Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06521762
- Sponsor's protocol ID
- 2000036896
- Status last verified
- Sep 2025
- First submitted
- 21 Jul 2024
- Last updated
- 14 Jan 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Etrasimod for Immune Checkpoint Inhibitor Diarrhea and Colitis
- ClinicalTrials.gov ID
- NCT06521762
- Acronym / sponsor ID
- 2000036896
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: The study was terminated early as no patients were enrolled.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Collaborators
- Pfizer
- Study start
- Jan 2026 (estimated)
- Primary completion
- Jan 2029 (estimated)
- Study completion
- Jan 2029 (estimated)
- First posted
- 26 Jul 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.
This is a randomized, double-blind, placebo-controlled, two-arm phase 2 study of etrasimod plus corticosteroids versus placebo plus corticosteroids for the treatment of IMDC CTCAE v5.0 grade ≥ 2 due to ICI therapy alone (α-PD-(L)1 monotherapy or combined with another ICI, such as α-CTLA-4 or α-LAG-3) or ICI plus an oral tyrosine kinase inhibitor that in the opinion of the treating physician requires treatment with corticosteroid-based immunosuppression and does not require immediate secondary immune suppression, such as vedolizumab or infliximab (or equivalent).
IMDC is one of the most common Immune Related Adverse Events (irAEs) from treatment with ICI. Current guidelines recommend steroid treatment for IMDC CTCAE grade ≥ 2, which requires temporary or permanent cessation of ICI therapy. Corticosteroids may interfere with the anti-tumor activity of ICIs and are therefore not co-administered. Strategies are needed to both reduce the dose and duration of corticosteroids needed for IMDC treatment and minimize the duration off ICI therapy before re-administering ICI (for those patients in whom it is deemed safe to rechallenge).
Detailed description
Participants will be screened as soon as IMDC is suspected but will not be randomized and administered the first dose of etrasimod or placebo until results from Clostridium difficile (C. difficile) and other intestinal infection assays are confirmed to be negative and stool calprotectin confirmed to be positive. If intestinal infectious studies are positive the participant will be excluded from the study. Due to the acute nature of some cases of IMDC (e.g., grade 4 IMDC), some participants may require initiation of corticosteroids before enrollment. In these cases, participants may be enrolled if the first dose of etrasimod or placebo can be administered within 96 hours of the first dose of corticosteroids. Participants will undergo flexible sigmoidoscopy or colonoscopy with colon biopsy prior to, within the first 7 days of starting study drug, which will be repeated 7 to 14 days after completing the last dose of study drug.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Etrasimod plus corticosteroids | Experimental | Drug: Etrasimod, Drug: CorticosteroidsParticipants will receive Etrasimod plus corticosteroids, to be given up to 120 days, to treat IMDC. |
| Placebo plus corticosteroids | Placebo comparator | Drug: Placebo, Drug: CorticosteroidsParticipants will receive Placebo plus corticosteroids, to be given up to 120 days, to treat IMDC. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Locally advanced unresectable or metastatic cancer
- Any tumor type being treated with either α-PD-(L)1 monotherapy or combination therapy containing α-PD-(L)1 and another ICI such as α-CTLA-4 or α-LAG-3 therapy.
- Patients receiving ICI(s) in combination with oral tyrosine kinase inhibitors (TKIs) may be enrolled if their diarrhea persists despite holding the TKI for 5 days and they meet the other eligibility criteria. These cases should be discussed with one of the study PIs. Patients receiving chemotherapy in combination with ICI(s) cannot be enrolled.
- Grade ≥ 2 IMDC requiring immunosuppression with corticosteroids as defined by at least grade 2 diarrhea and grade 2 colitis by CTCAE v5.0, which are defined in Appendix 3 (section 11.3) of the protocol.
- Positive stool calprotectin test
Key exclusion criteria (28 listed)
- Patients receiving ICIs in the adjuvant setting.
- Patients with severe hepatic impairment, as indicated by having a Child-Pugh C score.
- The following infectious complications:
- Patients with diabetes mellitus that meet the following criteria:
- Have a history of severe respiratory disease (i.e., pulmonary fibrosis, asthma, and chronic obstructive pulmonary disease) requiring supplemental oxygen not related to an underlying malignancy
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 |
|---|---|---|
| EtrasimodAlso: VELSIPITY2 mg/day oral tablet | Drug | Etrasimod plus corticosteroids |
| Placebomatching placebo oral tablet | Drug | Placebo plus corticosteroids |
| CorticosteroidsCorticosteroids will be given in conjunction with study drug or placebo | Drug | Etrasimod plus corticosteroids, Placebo plus corticosteroids |
Primary outcome
Average daily weight-adjusted dose of corticosteroids use
Time frame: up to day 120 or when a censoring event occurs
Average daily weight-adjusted dose of corticosteroids use (up to day 120 or when a censoring event occurs), accounting for both the weight-adjusted cumulative dose of steroids and the length of treatment.
6 secondary outcomes
Requirement for secondary immunosuppression
Time frame: up to day 120 or when a censoring event occurs
Mean time to improvement
Time frame: up to day 120 or when a censoring event occurs
Mean number of days without corticosteroids use
Time frame: up to day 120 or when a censoring event occurs
Safety and Tolerability Measured by Assessing Incidence and severity of adverse events of special interest.
Time frame: up to day 120 or when a censoring event occurs
Incidence and severity of laboratory abnormalities
Time frame: up to day 120 or when a censoring event occurs
Total count of clinically significant vital sign abnormalities
Time frame: up to day 120 or when a censoring event occurs
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 14 Jan 2026.
- 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.
Harriet Kluger, MD principal investigator
Yale University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Etrasimod and Corticosteroids in people with Immune Checkpoint Inhibitor-Related Diarrhea and Colitis, run by Yale University at 1 site in United States.
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 16 inclusion and 28 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 14 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Average daily weight-adjusted dose of corticosteroids use (time frame: up to day 120 or when a censoring event occurs). 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 14 Jan 2026.