Etrasimod + Corticosteroids for Colitis

Overseen By Harriet Kluger, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Yale University

Must be taking: Corticosteroids

Must not be taking: Anti-TNFα, Mycophenolate

Disqualifiers: Severe hepatic impairment, Diabetes, Cardiovascular, Infections, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

Duration: 17 weeks

96 Participants Needed

Trial Summary

What is the purpose of this trial?

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).

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you must stop taking your current medications, but it mentions that you cannot continue using certain drugs listed in Appendix 4 of the protocol. It is best to discuss your current medications with the study team to determine if any need to be stopped.

What data supports the effectiveness of the drug Etrasimod when used with corticosteroids for colitis?

Corticosteroids are known to help reduce inflammation and induce remission in ulcerative colitis, but they can have serious side effects. While there is no direct data on Etrasimod for colitis in the provided research, corticosteroids are a common and effective treatment for this condition. ^{1 2 3 4 5}

Is Etrasimod + Corticosteroids safe for treating colitis?

Corticosteroids, often used for colitis, can have side effects like increased risk of infections and other complications, but they are generally considered safe for short-term use. There is no specific safety data for Etrasimod in the provided research, but corticosteroids have been widely studied and used in inflammatory bowel disease treatment. ^{3 6 7 8 9}

How does the drug Etrasimod differ from other treatments for colitis?

Etrasimod is unique because it is an oral medication that works by modulating the immune system, specifically targeting certain receptors involved in inflammation, which is different from traditional treatments like corticosteroids that broadly suppress the immune response. This targeted approach may offer a new option for patients who do not respond well to existing therapies. ^{6 10 11 12 13}

Research Team

Harriet Kluger, MD

Principal Investigator

Yale University

Eligibility Criteria

This trial is for patients with grade ≥2 diarrhea and colitis caused by immune checkpoint inhibitors, used alone or with other treatments. Participants must need corticosteroid treatment but not immediate intense immunosuppression.

Inclusion Criteria

My cancer cannot be removed by surgery and has spread.

I need steroids for severe diarrhea and colitis.

I am willing and able to follow the study's medication and requirements.

Exclusion Criteria

I have a confirmed gut infection from a stool test.

I have had serious infections or widespread herpes.

Active psychiatric problems that could interfere with compliance with the study procedures

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (in-person)

Treatment

Participants receive Etrasimod or placebo plus corticosteroids for up to 120 days

17 weeks

Multiple visits (in-person) for drug administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person)

Treatment Details

Interventions

• Etrasimod

Trial Overview The study tests if etrasimod plus corticosteroids can better manage Immune Checkpoint Inhibitor Diarrhea and Colitis than a placebo plus corticosteroids, potentially reducing the total steroids needed.

Participant Groups

Group I: Etrasimod plus corticosteroids Experimental Treatment 2 Interventions

Participants will receive Etrasimod plus corticosteroids, to be given up to 120 days, to treat IMDC.

Group II: Placebo plus corticosteroids Placebo Group 2 Interventions

Participants will receive Placebo plus corticosteroids, to be given up to 120 days, to treat IMDC.

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

Pfizer

Industry Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

Findings from Research

Corticosteroids are the primary treatment for acute ulcerative colitis, but in cases where the disease does not respond, immunosuppressive therapies like azathioprine and cyclosporin may be necessary.

While these treatments can be effective, their potential side effects and the risk of long-term complications, such as cancer in patients with chronic extensive colitis, must be carefully considered.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of corticosteroids and immunosuppressive agents in ulcerative colitis. Connell, WR., Taylor, AC.[2019]

Immunosuppressant and biologic therapies for Crohn's disease and ulcerative colitis can lead to a range of adverse events, from mild symptoms to serious complications like infections and cancers, highlighting the importance of careful monitoring.

The review emphasizes the need for healthcare providers to engage in personalized risk-benefit discussions with patients regarding these therapies, considering individual risk factors to optimize treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events in IBD therapy: the 2018 update. Quezada, SM., McLean, LP., Cross, RK.[2019]

In a study involving 146 patients with active distal ulcerative colitis, budesonide enemas (2 mg/100 ml) showed similar efficacy to prednisolone enemas (25 mg/100 ml) in improving clinical symptoms and proctoscopy findings after 2 weeks of treatment.

Budesonide enemas did not significantly affect plasma cortisol levels, indicating a potentially safer profile compared to prednisolone, which reduced cortisol by about 30%, suggesting less impact on the hypothalamic-pituitary-adrenal axis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Budesonide enema in distal ulcerative colitis. A randomized dose-response trial with prednisolone enema as positive control. The Danish Budesonide Study Group. [2019]

References

1. United States pubmed.ncbi.nlm.nih.gov

Treatment of Ulcerative Colitis with Steroids (in Whom, How Long, What Dose, What Form). [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Cyclosporine and infliximab as rescue therapy for each other in patients with steroid-refractory ulcerative colitis. [2015]

3. England pubmed.ncbi.nlm.nih.gov

Budesonide MMX for the Induction of Remission of Mild to Moderate Ulcerative Colitis: A Pooled Safety Analysis. [2018]

4. England pubmed.ncbi.nlm.nih.gov

Outcomes and prediction of corticosteroid therapy after successive courses of ulcerative colitis treatments. [2018]

5. England pubmed.ncbi.nlm.nih.gov

Early corticosteroids requirement after the diagnosis of ulcerative colitis diagnosis can predict a more severe long-term course of the disease - a nationwide study of 1035 patients. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Safety of corticosteroids and immunosuppressive agents in ulcerative colitis. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

Oral prolonged release beclomethasone dipropionate and prednisone in the treatment of active ulcerative colitis: results from a double-blind, randomized, parallel group study. [2018]

8. England pubmed.ncbi.nlm.nih.gov

The Historical Role and Contemporary Use of Corticosteroids in Inflammatory Bowel Disease. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Adverse events in IBD therapy: the 2018 update. [2019]

10. United States pubmed.ncbi.nlm.nih.gov

Medical therapy for ulcerative colitis in childhood. [2017]

11. England pubmed.ncbi.nlm.nih.gov

Budesonide versus prednisolone retention enemas in active distal ulcerative colitis. [2019]

12. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Randomized controlled trials in steroid dependent and in severe colitis. [2019]

13. England pubmed.ncbi.nlm.nih.gov

Budesonide enema in distal ulcerative colitis. A randomized dose-response trial with prednisolone enema as positive control. The Danish Budesonide Study Group. [2019]