Checkpoint Inhibitor-induced Liver Injury

Immune-Mediated Hepatitis Clinical Trial

— ChILI  

Official title:

Checkpoint Inhibitor-induced Liver Injury Study (ChILI)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04476563
• Other study ID #: 20034
• Status: Recruiting
• Start date: October 13, 2020
• Est. completion date: August 2023

Study information

• Verified date: November 2022
• Source: University of Nottingham
• Contact: Guruprasad Padur Aithal, MBBS, FRCP, PhD
• Phone: 0115 823 1074
• Email: guru.aithal[@]nottingham.ac.uk
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

In this multi-center prospective observational study, the investigators plan to identify the incidence and risk factors for checkpoint inhibitor-induced liver injury and characterize biochemical, genetic, immunological, and histological features associated with it.

Description:

Checkpoint inhibitor-induced liver injury (ChILI) is a new incompletely understood category of hepatotoxicity which is distinct from other types of drug-induced liver injury (DILI) such as direct or idiosyncratic DILI. The data regarding the incidence and risk factors is lacking. Therefore, 'in-depth phenotyping' together with data from the control group exposed to checkpoint inhibitors (CPI) is necessary to develop refined algorithms incorporating CPI-related factors, host genetic and environmental risk factors that would enable pre-empting ChILI.

The aim of the study is to enroll two deeply phenotyped cohorts (patients who developed ChILI and patients who are starting checkpoint inhibitors) and obtain biological samples at multiple time points.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 160
• Est. completion date: August 2023
• Est. primary completion date: August 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

Both patient groups and control group:

• Able to give written informed consent OR Potential participants who have developed encephalopathy related to ChILI as a response to checkpoint inhibitor therapy, who lack the capacity to give written informed consent and have a consultee (personal or nominated) - for ChILI patient group only

ChILI group:

Patients who developed checkpoint inhibitor-induced liver injury and meet the following criteria:

1. Meets one of the following analytical thresholds at enrolment (visit 1)

• Alanine transaminase (ALT) exceeding 5 times the upper limit of normal (ULN) OR

• ALT exceeding 3 times ULN plus bilirubin exceeding 2 times ULN OR

• Alkaline phosphatase (ALP) exceeding 2 times ULN with accompanying elevations of gamma-glutamyl transferase in the absence of known bone metastases driving the rise in ALP level

2. Absence of other known causes of liver injury after detailed investigations

Patients who developed ChILI but did not meet the above criteria at enrolment or who were found to have a different cause for their liver injury after further investigations will be excluded from the analysis

Control group:

Consecutive patients with cancer who have a clinical indication to start checkpoint inhibitors. A small proportion of patients will develop ChILI following their checkpoint inhibitor treatment and will be classified as cases.

Exclusion Criteria:

• Patients who are treated with cytotoxic chemotherapy concurrently with checkpoint inhibitors.

• On the judgment of chief investigator that the person has certain alternative explanations to the acute event (rather than ChILI).

Related Conditions & MeSH terms

• Hepatitis
• Immune-Mediated Hepatitis

Intervention

Diagnostic Test:
• Obtaining biological samples
Biological samples (blood, urine, stool). Liver tissue will be obtained from ChILI group when clinically indicated

Locations

Country	Name	City	State
United Kingdom	University of Nottingham	Nottingham

Sponsors (2)

Lead Sponsor	Collaborator
University of Nottingham	Pfizer

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of checkpoint inhibitor-induced liver injury (ChILI) and other immune-mediated adverse reactions		3 years
Primary	Identify novel biomarkers associated with the diagnosis of ChILI	The investigators plan assessment of proposed circulating biomarkers including cytokines, microRNAs (miR-122, miR-4270 and miR-4463), total cytokeratin 18 (K18), macrophage colony-stimulating factor receptor (MCSFR), and any others identified in subsequent publications and measure their diagnostic and prognostic accuracy using the area under the receiver operating curve (AUROC).	3 years