NCT05345847

Steroid Sparing in Immune Related Hepatitis (irH)

A Study to Evaluate the Efficacy and Safety of Steroid Sparing Strategy in Immune Related Hepatitis

• Status: Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 56 (estimated)
• Sponsor: AHS Cancer Control Alberta · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

A multi-centre, randomized, non-inferiority trial in patients with irH, randomized to receive either close surveillance with corticosteroid rescue therapy or early high dose corticosteroids.

Detailed description

Immune checkpoint inhibitors (ICIs) are a class of immunotherapy drugs that helps signal to the immune system to seek out and destroy cancer. However despite showing clinical benefit over traditional chemotherapy, ICIs can lead to certain toxicities called immune-related adverse events (irAEs). One of these irAEs is immunotherapy related hepatitis (irH) and is an important and less common toxicity of ICI therapy that could develop into a rare but serious complication of sudden liver failure. The management of irH includes high-dose steroids and use of steroids is not without significant side effects, especially when used for longer term. Given the potential consequences of high dose long-term corticosteroids along with the implications of permanently discontinuing therapy, it is necessary to better understand the pathophysiology associated with irH and clarify the role of steroids in managing this patient population. It is especially important to determine which patients require intervention with steroids and other immunosuppression versus those that could simply be monitored for spontaneous resolution. The results of this trial will identify predictors of irH resolution and inform judicious use of corticosteroids and immunosuppressive therapy for this at-risk population. This study has been designed as a randomized, phase II non-inferiority study to investigate the efficacy of an active surveillance with steroid rescue strategy compared to early initiation of corticosteroids in the setting of irH secondary to ICIs. The study treatment period is 12 weeks with twice weekly liver enzyme function assessments. Once irH has improved to by one CTCAE grade (i.e. grade 3 to 2, or grade 2 to 1), this can be decreased to weekly assessment. For patients who continue to have asymptomatic liver enzyme elevation of grade 2 or higher, maintaining a surveillance strategy beyond this point is not appropriate, as investigators may wish to adjust therapy, especially if this is resulting in delay in resuming ICI. In this setting, weekly liver enzyme assessment will continue. The frequency of liver enzyme monitoring can be increased at the discretion of the investigator or hepatologist. Following the initial 12-week period, further surveillance with an observation period consisting of every 3 weekly assessments will be completed for a total of 40 weeks (total study duration of 52 weeks). Participants will continue follow up for a total of one year to allow the capture longer term data as well as other endpoints.

Conditions

• Hepatitis Immune

Interventions

Type	Name	Description
OTHER	Active Surveillance	Close monitoring of liver enzymes with steroid rescue strategy (watch and wait approach)
OTHER	Early initiation	Immediate start of high-dose steroids

Timeline

• Start date: 2025-12-08
• Primary completion: 2028-02-08
• Completion: 2029-02-08
• First posted: 2022-04-26
• Last updated: 2026-03-23

Locations

1 site across 1 country: Canada