Etrasimod for Immune Checkpoint Inhibitor Diarrhea and Colitis
NCT Number: NCT06521762
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE2
Conditions: Immune Checkpoint Inhibitor-Related Diarrhea and Colitis
Interventions: DRUG: Etrasimod|DRUG: Placebo|DRUG: Corticosteroids
Sponsor: Yale University
Collaborators: Pfizer
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 96
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: DOUBLE (PARTICIPANT, INVESTIGATOR)|Primary Purpose: TREATMENT
Start Date: 2024-08
Completion Date: 2026-08
Locations: Yale Cancer Center, New Haven, Connecticut, 06510, United States

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 Immune Checkpoint Inhibitor Diarrhea and Colitis (IMDC) CTCAE v5.0 grade ≥ 2 due to immune checkpoint inhibitors (ICI) therapy alone or combined with another ICI or ICI plus chemotherapy that in the opinion of the treating physician requires treatment with corticosteroid-based immunosuppression and does not require immediate secondary immune suppression.

The purpose of this study is to improve the treatment of IMDC in people taking ICIs and find out if etrasimod combined with corticosteroids is more effective than a placebo combined with corticosteroids at lowering the total number of corticosteroids needed to treat IMDC.

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 that ICI therapy be stopped. Corticosteroids may interfere with ICIs and cannot be given at the same time, Strategies are needed to reduce the dose and duration of corticosteroids needed for IMDC treatment and minimize the duration that patients have to be off ICI therapy. (ICIs are a type of immunotherapy.)

Primary Outcome Measures: 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., up to day 120 or when a censoring event occurs
Secondary Outcome Measures: 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., 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, up to day 120 or when a censoring event occurs|Mean duration of corticosteroids use, Mean duration of corticosteroids use in Days., up to day 120 or when a censoring event occurs|Safety and Tolerability Measured by Assessing Serious Adverse Events (SAEs)and Adverse Events (AEs), Number of participants that experience any AEs and SAEs will be examined with (National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v 4.03., 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., 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, up to day 120 or when a censoring event occurs|Change from baseline in creatinine, Participants that had at least a 50% increase in creatinine from baseline, baseline and up to day 120 or when a censoring event occurs|Change from baseline in liver enzymes, Participants that had and increase in Aspartate Transferase (AST) and Alanine transaminase (ALT) over three times the upper level of normal from baseline, baseline and up to day 120 or when a censoring event occurs|Change from baseline in hemogloblin (Hb), Participants that had decrease in Hb by 2 grams/deciliter (g/dL) from baseline, baseline and up to day 120 or when a censoring event occurs|Change from baseline in platelet count, Participants that had decrease in platelet counts below 100,000 platelets/microliter (platelets/mcL) from baseline, baseline and 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, up to day 120 or when a censoring event occurs|Change in vital signs- systolic blood pressure, Mean change in systolic blood pressure in mmHg, baseline and up to day 120 or when a censoring event occurs|Change in vital signs- diastolic blood pressure, Mean change in diastolic blood pressure in mmHg, baseline and up to day 120 or when a censoring event occurs|Change in vital signs- body temperature, Mean change in body temperature in degrees Fahrenheit, baseline and up to day 120 or when a censoring event occurs|Change in vital signs- heart rate, Mean change in heart rate measured in beats per minute, baseline and up to day 120 or when a censoring event occurs|Change in vital signs- respiratory rate, Mean change in respiratory rate measured in breaths per minute, baseline and up to day 120 or when a censoring event occurs|Change in vital signs- oxygen saturation (SpO2), Mean change in percent oxygen saturation assessed using a pulse oximeter, baseline and up to day 120 or when a censoring event occurs