NCT06470997

Brief Summary

Identify specific blood biomarkers for hepatitis induced by immune checkpoint inhibitors in comparison to idiopathic autoimmune hepatitis.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
60

participants targeted

Target at P25-P50 for all trials

Timeline
9mo left

Started Jul 2024

Typical duration for all trials

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress71%
Jul 2024Jan 2027

First Submitted

Initial submission to the registry

June 7, 2024

Completed
17 days until next milestone

First Posted

Study publicly available on registry

June 24, 2024

Completed
23 days until next milestone

Study Start

First participant enrolled

July 17, 2024

Completed
2.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 18, 2027

Expected
13 days until next milestone

Study Completion

Last participant's last visit for all outcomes

January 31, 2027

Last Updated

November 21, 2025

Status Verified

November 1, 2025

Enrollment Period

2.5 years

First QC Date

June 7, 2024

Last Update Submit

November 20, 2025

Conditions

Immune-mediated Hepatitis

Keywords

proteomic analysisblood biomarkerimmune-mediated hepatitis secondary to immune checkpoint inhibitorsidiopathic autoimmune hepatitis

Outcome Measures

Primary Outcomes (1)

  • Determination of the area under the ROC (Receiver Operation characteristic) curve for hepatitis.

    Sensitivity/specialty curve of blood biomarkers identification and expression level by proteomic analysis, specific to immunotherapy-induced hepatitis (CHILI group), versus idiopathic autoimmune hepatitis (control group).

    Baseline

Secondary Outcomes (2)

  • Determination of the area under the ROC (Receiver Operation characteristic) curve for treatment response

    Baseline, day 14, day 28, month 3, month 6

  • Responses to treatments

    Day 28

Study Arms (2)

CHILI : hepatitis induced by immune checkpoint inhibitors

Patient with immunotherapy-induced hepatitis

Biological: Blood sample collectionProcedure: Liver biopsy

Control group: idiopathic autoimmune hepatitis

Patient with idiopathic autoimmune hepatitis

Biological: Blood sample collectionProcedure: Liver biopsy

Interventions

Blood sample collectionBIOLOGICAL

6 collections of 5mL blood samples as part of usual care (pre-inclusion visit at Day-7, inclusion visit at Day 0, visit1 at Day 14, visit2 at Day 28, visit3 at Day 90, visit4 at 6 months) and 5 blood sample collections of 5 mL for proteomic analysis in the context of research (inclusion visit at Day 0, visit1 at Day 14, visit2 at Day 28, visit3 at Day 90, visit4 at 6 months)

CHILI : hepatitis induced by immune checkpoint inhibitorsControl group: idiopathic autoimmune hepatitis
Liver biopsyPROCEDURE

1 liver biopsy performed as part of routine care and 1 additional sample for research: transparietal needle biopsy under ultrasound identification under local anesthesia by a radiologist, 1 to 2 cm per core taken, 2 cores are taken.

CHILI : hepatitis induced by immune checkpoint inhibitorsControl group: idiopathic autoimmune hepatitis

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodNon-Probability Sample
Study Population

CHILI group: patients with hepatitis induced by immune checkpoint inhibitors Control group: patients with idiopathic autoimmune hepatitis

You may qualify if:

  • Patient \> 18 years old
  • Patient treated with immune checkpoint inhibitors (ICI) alone or in combination
  • Patient suffering from Hepatitis secondary to immune checkpoint inhibitors (ICI) grade 3 or 4 Common Terminology Criteria For Adverse Events (CTCAE)\*
  • Treatment with corticosteroids or Ursodeoxycholic acid (UDCA) not started, or started less than 30 days ago
  • Grade 3 or 4 hepatitis: increase in transaminases and/or alkaline phosphatases ≥ 5 x Upper Limit of Normal (ULN) or total bilirubin ≥ 3
  • Patient \> 18 years old
  • Patient suffering from Primary Biliary Cholangitis (PBC)\* or Autoimmune Hepatitis (AIH)\*\* or Primary Sclerosing Cholangitis (PSC) \*\*\*
  • Primary Biliary Cholangitis (PBC)\* diagnosis :
  • Association of at least 2 of the following 3 criteria :
  • Cholestasis (PAL \> 1.5N, Gamma GT \> 3N) chronic (\> 6 months) without ultrasound abnormality of the bile ducts.
  • M2 type anti-mitochondria Ab \> 1/40th
  • Characteristic histological lesions (non-suppurative destructive cholangitis) or compatible (portal inflammation, granulomas, ductular proliferation, ductopenia, cholestasis).
  • \*\* AIH diagnosis : ALT \> 5 N / Ig G \> 1.5 - 2 N or anti-smooth muscle ≥ 1/80 / Interface hepatitis of marked intensity The Hepactic Activity Index (HAI) score makes it possible to confirm the diagnosis when all the diagnostic criteria are not met.
  • \*\*\* PSC diagnosis: presence of chronic cholestasis (alkaline phosphatase \> 1.5 N or GGT \> 3 N) and typical abnormalities of the bile ducts on cholangio-MRI (Magnetic Resonance Imaging), and in the absence of cause of secondary sclerosing cholangitis
  • Treatment with corticosteroids or Ursodeoxycholic acid (UDCA) not initiated, or started less than 30 days ago
  • +9 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

CHU de Montpellier

Montpellier, France, 34295, France

RECRUITING

Related Publications (9)

  • De Martin E, Michot JM, Rosmorduc O, Guettier C, Samuel D. Liver toxicity as a limiting factor to the increasing use of immune checkpoint inhibitors. JHEP Rep. 2020 Aug 11;2(6):100170. doi: 10.1016/j.jhepr.2020.100170. eCollection 2020 Dec.

    PMID: 33205034BACKGROUND

  • Champiat S, Lambotte O, Barreau E, Belkhir R, Berdelou A, Carbonnel F, Cauquil C, Chanson P, Collins M, Durrbach A, Ederhy S, Feuillet S, Francois H, Lazarovici J, Le Pavec J, De Martin E, Mateus C, Michot JM, Samuel D, Soria JC, Robert C, Eggermont A, Marabelle A. Management of immune checkpoint blockade dysimmune toxicities: a collaborative position paper. Ann Oncol. 2016 Apr;27(4):559-74. doi: 10.1093/annonc/mdv623. Epub 2015 Dec 28.

    PMID: 26715621BACKGROUND

  • Peeraphatdit TB, Wang J, Odenwald MA, Hu S, Hart J, Charlton MR. Hepatotoxicity From Immune Checkpoint Inhibitors: A Systematic Review and Management Recommendation. Hepatology. 2020 Jul;72(1):315-329. doi: 10.1002/hep.31227.

    PMID: 32167613BACKGROUND

  • Haanen J, Obeid M, Spain L, Carbonnel F, Wang Y, Robert C, Lyon AR, Wick W, Kostine M, Peters S, Jordan K, Larkin J; ESMO Guidelines Committee. Electronic address: clinicalguidelines@esmo.org. Management of toxicities from immunotherapy: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2022 Dec;33(12):1217-1238. doi: 10.1016/j.annonc.2022.10.001. Epub 2022 Oct 18. No abstract available.

    PMID: 36270461BACKGROUND

  • Zen Y, Yeh MM. Hepatotoxicity of immune checkpoint inhibitors: a histology study of seven cases in comparison with autoimmune hepatitis and idiosyncratic drug-induced liver injury. Mod Pathol. 2018 Jun;31(6):965-973. doi: 10.1038/s41379-018-0013-y. Epub 2018 Feb 5.

    PMID: 29403081BACKGROUND

  • Hountondji L, Ferreira De Matos C, Lebosse F, Quantin X, Lesage C, Palassin P, Rivet V, Faure S, Pageaux GP, Assenat E, Alric L, Zahhaf A, Larrey D, Witkowski Durand Viel P, Riviere B, Janick S, Dalle S, Maria ATJ, Comont T, Meunier L. Clinical pattern of checkpoint inhibitor-induced liver injury in a multicentre cohort. JHEP Rep. 2023 Mar 7;5(6):100719. doi: 10.1016/j.jhepr.2023.100719. eCollection 2023 Jun.

    PMID: 37138674BACKGROUND

  • Coukos A, Vionnet J, Obeid M, Bouchaab H, Peters S, Latifyan S, Wicky A, Michielin O, Chtioui H, Moradpour D, Fasquelle F, Sempoux C, Fraga M. Systematic comparison with autoimmune liver disease identifies specific histological features of immune checkpoint inhibitor-related adverse events. J Immunother Cancer. 2022 Oct;10(10):e005635. doi: 10.1136/jitc-2022-005635.

    PMID: 36283734BACKGROUND

  • Gudd CLC, Au L, Triantafyllou E, Shum B, Liu T, Nathwani R, Kumar N, Mukherjee S, Dhar A, Woollard KJ, Yone Y, Pinato DJ, Thursz MR, Goldin RD, Gore ME, Larkin J, Khamri W, Antoniades CG, Turajlic S, Possamai LA. Activation and transcriptional profile of monocytes and CD8+ T cells are altered in checkpoint inhibitor-related hepatitis. J Hepatol. 2021 Jul;75(1):177-189. doi: 10.1016/j.jhep.2021.02.008. Epub 2021 Feb 22.

    PMID: 33631227BACKGROUND

  • Yoshimura K, Tamano Y, Nguyen Canh H, Zihan L, Le Thanh D, Sato Y, Terashima T, Shimoda S, Harada K. A novel pathologic marker, indoleamine 2,3-dioxygenase 1, for the cholangiopathy of immune checkpoint inhibitors-induced immune mediated hepatotoxicity as adverse events and the prediction of additional ursodeoxycholic acid treatment. Med Mol Morphol. 2023 Jun;56(2):106-115. doi: 10.1007/s00795-022-00344-7. Epub 2023 Jan 4.

    PMID: 36599971BACKGROUND

Study Officials

  • Lucy MEUNIER, MD

    University Hospital, Montpellier

    STUDY DIRECTOR

Central Study Contacts

Lucy MEUNIER, MD

CONTACT

0467330224lucy-meunier@chu-montpellier.fr

Lina HOUNTONDJI, MD

CONTACT

l-hountondji@chu-montpellier.fr

Study Design

Study Type
observational
Observational Model
OTHER
Time Perspective
PROSPECTIVE
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 7, 2024

First Posted

June 24, 2024

Study Start

July 17, 2024

Primary Completion (Estimated)

January 18, 2027

Study Completion (Estimated)

January 31, 2027

Last Updated

November 21, 2025

Record last verified: 2025-11

Locations

FR(1)