Hepatitis ImmuneNCT05345847
Steroid Sparing in Immune Related Hepatitis (irH)
A study testing Active Surveillance and Early initiation in people with Hepatitis Immune, run by AHS Cancer Control Alberta at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatitis Immune
- What is being tested?
- Active Surveillance and Early initiation
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 56 participants
- Where
- 1 siteCanada
- Study dates
- 8 Dec 2025to 8 Feb 2029
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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
- Patients must be 18 years of age, or older on the day of signing informed consent.
- Patients must be capable of providing consent to enrolment and treatment.
- Patients with a performance status of ECOG 0-2 will be eligible for enrolment.
- Patients with histologically confirmed cancer receiving anti-PD1 or anti-PDL1 monoclonal antibody ICI therapy, either alone or in combination with anti-CTLA-4 monoclonal antibody ICI therapy who develop CTCAEv5.0 grade 2 or grade 3 hepatitis that has developed on, or after, ICI therapy and is felt to be treatment related (irH). Patients must be enrolled on trial within 10 days of diagnosis of grade 2 or grade 3 hepatotoxicity.
- Absence of any condition hampering compliance with the study protocol and follow- up schedule; those conditions should be discussed with the patient before registration in the trial.
- Assessment by the Roussel Uclaf Causality Assessment Method (RUCAM) ≥6 showing probable relationship between ICI and liver injury (appendix)
Who cannot join
- History underlying liver disease, including, but not limited to: hepatitis B, C, autoimmune hepatitis, primary biliary sclerosis, hemochromatosis, primary sclerosis cholangitis, portal vein thrombosis, Budd Chiari syndrome, alcohol induced hepatitis, suspected drug-induced liver injury from other cause (e.g. acetaminophen, antibiotics, statins, methyldopa, non-prescription herbs, see NIH LiverTox website https://livertox.nih.gov for comprehensive list).
- If undertaken, liver biopsy supporting a cause of liver dysfunction other than irH
- Patients with an indication for systemic immunosuppressive medications or corticosteroids. Patients with CTCAEv5.0 grade ≥2 irAE's other than irH (ie. colitis, pneumonitis, rash, etc.) are not eligible for trial, with the exception of endocrinopathies that are being treated with hormone replacement alone and not systemic immunosuppressive medications or corticosteroids.
- Abnormal International Normalization Ratio (INR) at baseline (≥1.5) and bilirubin ≥60, ALT of ≥10X.
- Previous use of targeted therapies for treatment of malignancy (e.g. BRAF, MEK, EGFR, and VEGF inhibitors) or current treatment with chemotherapy
- Present use of warfarin.
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- Diagnosis of immunodeficiency.
- Current use of immunosuppressive medication, EXCEPT for the following: a. intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection); b. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).
- Known prior severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (CTCAEv5.0 Grade ≥ 3).
- Other severe acute or chronic medical conditions including inflammatory bowel disease, immune pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Amy A contact
Canada1 site, 1 recruiting
- Recruiting
Arthur J.E. Child Comprehensive Cancer Centre
Calgary, Alberta, T2N 5G2
Omar F Khan, MD
About this study
Official title: A Study to Evaluate the Efficacy and Safety of Steroid Sparing Strategy in Immune Related Hepatitis
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.
Read the 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
- Being tested
- Active Surveillance, Early initiation
- Keywords
- immune related hepatitis, steroid sparing
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Active SurveillanceOther
Close monitoring of liver enzymes with steroid rescue strategy (watch and wait approach)
Early initiationOther
Immediate start of high-dose steroids
| Study group | Role | What they receive |
|---|---|---|
| 1- Active Surveillance | Experimental | Active surveillance with rescue corticosteroids Receives: Other: Active Surveillance |
| 2- Early initiation of steroid (Standard) | Active comparator | Early intervention with high-dose steroids Receives: Other: Early initiation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Resolution of biochemical abnormalities in grade 2 and grade 3 irH at 12 weeks.
The primary objective of this clinical trial is to determine if active surveillance with steroid salvage is a non-inferior strategy in grade 2 and grade 3 irH in patients without evidence of liver dysfunction. Resolution will be defined as improved in irH to grade ≤1. This was chosen as a clinically significant endpoint as it is often used by oncologists to determine if patients may resume ICI therapy. Assessment and grading will be completed by the investigator according to CTCAEv5.0
Measured: 12 weeks
Secondary outcomes (5)
Safety of Steroid Sparing Strategy
To evaluate the safety of surveillance strategy based on rates of hospitalization, ICU admission, development of clinically significant liver failure (e.g. decompensated hepatic failure) and death.
Measured: 1 year
Total steroid usage
Total steroid usage (defined as the total amount of prednisone or prednisone equivalent in mg required over the study period).
Measured: 1 year
Development of immune related adverse events (irAE's) other than irH.
Defined as the emergence of adverse events that were not present at study baseline that are deemed by the investigator to be related to prior use of immune checkpoint inhibitors. Causality will be investigator assessed and graded according to CTCAEv5.0.
Measured: 1 year
Re-initiation of immune checkpoint inhibitor therapy.
The proportion of patients in each study arm that are re-treated with an immune checkpoint inhibitor.
Measured: 1 year
The time elapsed between randomization and tumor progression (radiographically or clinically) or death from any cause
Progression free survival
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Apr 2022
- Study start8 Dec 2025
- Primary completion8 Feb 2028 (estimated)
- Study completion8 Feb 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatitis ImmuneStudies 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 56 participants (estimated)
Sponsor and investigators
- Lead sponsor
- AHS Cancer Control Alberta
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Omar Khan, MD, Principal investigator, AHS Cancer Control Alberta
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05345847
- Sponsor's protocol ID
- IMPACT 7.0
- Status last verified
- Mar 2026
- First submitted
- 23 Mar 2022
- Last updated
- 23 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- 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 23 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Study to Evaluate the Efficacy and Safety of Steroid Sparing Strategy in Immune Related Hepatitis
- ClinicalTrials.gov ID
- NCT05345847
- Acronym / sponsor ID
- IMPACT 7.0
- Conditions
- Hepatitis Immune
- Keywords
- immune related hepatitis, steroid sparing
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 56 participants (estimated)
- Lead sponsor
- AHS Cancer Control AlbertaUniversity, hospital or other
- Study start
- 8 Dec 2025 (actual)
- Primary completion
- 8 Feb 2028 (estimated)
- Study completion
- 8 Feb 2029 (estimated)
- First posted
- 26 Apr 2022 (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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1- Active Surveillance | Experimental | Other: Active SurveillanceActive surveillance with rescue corticosteroids |
| 2- Early initiation of steroid (Standard) | Active comparator | Other: Early initiationEarly intervention with high-dose steroids |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Patients must be 18 years of age, or older on the day of signing informed consent.
- Patients must be capable of providing consent to enrolment and treatment.
- Patients with a performance status of ECOG 0-2 will be eligible for enrolment.
- Patients with histologically confirmed cancer receiving anti-PD1 or anti-PDL1 monoclonal antibody ICI therapy, either alone or in combination with anti-CTLA-4 monoclonal antibody ICI therapy who develop CTCAEv5.0 grade 2 or grade 3 hepatitis that has developed on, or after, ICI therapy and is felt to be treatment related (irH). Patients must be enrolled on trial within 10 days of diagnosis of grade 2 or grade 3 hepatotoxicity.
- Absence of any condition hampering compliance with the study protocol and follow- up schedule; those conditions should be discussed with the patient before registration in the trial.
Key exclusion criteria (10 listed)
- History underlying liver disease, including, but not limited to: hepatitis B, C, autoimmune hepatitis, primary biliary sclerosis, hemochromatosis, primary sclerosis cholangitis, portal vein thrombosis, Budd Chiari syndrome, alcohol induced hepatitis, suspected drug-induced liver injury from other cause (e.g. acetaminophen, antibiotics, statins, methyldopa, non-prescription herbs, see NIH LiverTox website https://livertox.nih.gov for comprehensive list).
- If undertaken, liver biopsy supporting a cause of liver dysfunction other than irH
- Patients with an indication for systemic immunosuppressive medications or corticosteroids. Patients with CTCAEv5.0 grade ≥2 irAE's other than irH (ie. colitis, pneumonitis, rash, etc.) are not eligible for trial, with the exception of endocrinopathies that are being treated with hormone replacement alone and not systemic immunosuppressive medications or corticosteroids.
- Abnormal International Normalization Ratio (INR) at baseline (≥1.5) and bilirubin ≥60, ALT of ≥10X.
- Previous use of targeted therapies for treatment of malignancy (e.g. BRAF, MEK, EGFR, and VEGF inhibitors) or current treatment with chemotherapy
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 |
|---|---|---|
| Active SurveillanceClose monitoring of liver enzymes with steroid rescue strategy (watch and wait approach) | Other | 1- Active Surveillance |
| Early initiationImmediate start of high-dose steroids | Other | 2- Early initiation of steroid (Standard) |
Primary outcome
Resolution of biochemical abnormalities in grade 2 and grade 3 irH at 12 weeks.
Time frame: 12 weeks
The primary objective of this clinical trial is to determine if active surveillance with steroid salvage is a non-inferior strategy in grade 2 and grade 3 irH in patients without evidence of liver dysfunction. Resolution will be defined as improved in irH to grade ≤1. This was chosen as a clinically significant endpoint as it is often used by oncologists to determine if patients may resume ICI therapy. Assessment and grading will be completed by the investigator according to CTCAEv5.0
5 secondary outcomes
Safety of Steroid Sparing Strategy
Time frame: 1 year
Total steroid usage
Time frame: 1 year
Development of immune related adverse events (irAE's) other than irH.
Time frame: 1 year
Re-initiation of immune checkpoint inhibitor therapy.
Time frame: 1 year
The time elapsed between randomization and tumor progression (radiographically or clinically) or death from any cause
Time frame: 1 year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Mar 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.
Amy A contact
Omar Khan, MD principal investigator
AHS Cancer Control Alberta
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Active Surveillance and Early initiation in people with Hepatitis Immune, run by AHS Cancer Control Alberta at 1 site in Canada.
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 10 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: looking for participants now, as of the sponsor's last update on 23 Mar 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 Canada. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Omar F Khan, MD ((587) 231-5082, Omar.Khan@cancercarealberta.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Resolution of biochemical abnormalities in grade 2 and grade 3 irH at 12 weeks. (time frame: 12 weeks). 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 23 Mar 2026.