A Phase 2 Open-label Single-arm Trial of JAK1 Inhibitor for the Treatment of Large Inflammatory Hepatocellular Adenomas (JAKIH)

December 19, 2025 updated by: Assistance Publique - Hôpitaux de Paris
Hepatocellular adenomas (HCA) are tumors rare benign hepatic infections that develop on a liver normal and in young women taking a estrogen-based contraception. The main molecular subgroup of AHCs is the AHC subgroup inflammatory, which are associated with a risk of bleeding from the tumor and malignant transformation. Therefore, most of women with large inflammatory AHC (>5 cm) require liver resection which can be associated with morbidity and aesthetic problems, and rarely to mortality. On the basis of the knowledge of the molecular classification of AHCs humans and preclinical data testing the JAK1/2 inhibitors, we hypothesize that a short duration of treatment with the inhibitor of JAK1/2 (baricitinib) may be effective in patients with large inflammatory AHC size.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Hepatocellular adenomas (HCA) are tumors rare benign hepatic infections that develop on a liver normal and in young women taking a estrogen-based contraception. The main molecular subgroup of AHCs is the AHC subgroup inflammatory, characterized by activation of the pathway JAK/STAT due to mutations in IL6ST, STAT3, FRK, JAK1 or GNAS, with inflammatory infiltrates at histology. Hepatocellular adenomas are associated with a risk of bleeding from the tumor and malignant transformation. Therefore, most of women with large inflammatory AHC (>5 cm) require liver resection which can be associated with morbidity and aesthetic problems, and rarely to mortality. On the basis of the knowledge of the molecular classification of AHCs humans and preclinical data testing the JAK1/2 inhibitors, we hypothesize that a short duration of treatment with the inhibitor of JAK1/2 (baricitinib) may be effective in patients with large inflammatory AHC size.

Study Type

Interventional

Enrollment (Estimated)

25

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Women (or male with inflammatory HCA considered as non resectable whatever the size of the HCA)
  • Written informed consent for participation in study
  • Histologically proven hepatocellular adenoma (confirmed by a centralized reviewing) with available FFPE
  • At least one HCA of inflammatory subtype confirmed at histology and immunohistochemistry (CRP or SAA immunohistochemistry) by a centralized reviewing
  • At least one HCA of more than 5 cm at imaging of inflammatory subtype (if the HCA of more than 5 cm is not the same HCA proved as inflammatory at histology this HCA should harbored the same imaging features than the HCA with available histology) for women.
  • Diagnosed at histology over the last 5 years
  • Absence of desire of pregnancy while treated by baricitinib and for at least 4 weeks following the last dose of investigational product
  • Females of childbearing potential should have a contraception (without estrogen) when engaging in sexual intercourse with a male partner while treated by baricitinib and for at least 4 weeks following the last dose of investigational product. In case of oral contraception, patients should have been using it for a minimum of one month before the beginning of the treatment. A woman is considered of childbearing potential (WOCBP), i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause.
  • Male when engaging in sexual intercourse with a female partner shoud have a contraception while treated by baricitinib and for at least 4 weeks following the last dose of investigational product A man is considered fertile after puberty unless permanently sterile by bilateral orchiectomy
  • Past infection of Varicella zona Virus confirmed by serology or vaccine against Varicella zona Virus done more than 4 weeks before the inclusion
  • Coverage for medical insurance

Exclusion criteria:

  • < 18 years old and > 65 years old
  • Pregnancy or breastfeeding woman
  • Ongoing estrogen-based contraception at inclusion
  • Patient on AME (state medical aid)
  • Have a current or recent (<4 weeks prior to inclusion) clinically serious viral, bacterial, fungal, or parasitic infection (Note: For example, a recent viral upper respiratory tract infection or uncomplicated urinary tract infection should not be considered clinically serious).
  • Have screening electrocardiogram (ECG) abnormalities that, in the opinion of the investigator or the sponsor, are clinically significant and indicate an unacceptable risk for the patient's participation in the study.
  • Thrombocytopenia < 100 000/mm3
  • Neutropenia < 1200/mm3
  • Lymphopénia < 750/mm3
  • Anemia < 9 g/dl
  • Concomitant use of immunosuppressive treatment such as methotrexate, azathioprine, mycophenolate (at the exception of corticosteroid)
  • Have received etanercept, infliximab, certolizumab, adalimumab, golimumab, or anakinra within 12 weeks of screening; tocilizumab, abatacept, ustekinumab, rituximab, belimumab, or any other B cell targeted therapies (approved or investigational) within 24 weeks of screening; or any other biologic therapy within 4 weeks of inclusion, whichever is longer.
  • ASAT > 5 times upper fold of the normal or ALAT > 5 times upper fold of the normal or total bilirubin > upper 1.5 fold of the normal
  • hepatic impairment defined by Child Pugh B or C
  • Have evidence of active tuberculosis as documented by medical history, clinical symptoms, and abnormal chest x-ray at screening together with positive quantiferon or T spot test or positive culture
  • Have evidence of latent TB (as documented by a positive quantiferon or T spot test, no clinical symptoms consistent with active TB, and a normal chest x-ray at screening, or as outlined below) unless patient completes at least 4 weeks of appropriate treatment prior to inclusion and agrees to complete the remainder of treatment while in the trial.
  • Renal impairment with estimated creatinine clearance < 50 ml/mn (Cockroft and Gault formula)
  • Have had any major surgery within 8 weeks prior to screening or will require major
  • surgery during the study that, in the opinion of the investigator in consultation with the principal investigator, would pose an unacceptable risk to the patient.
  • Past history of lymphoproliferative disease
  • Past history of acute myocardial infection or unstable angina
  • Past history of stroke (including transient ischemic attack)
  • Uncontrolled hypertension defined as sustained blood pressure (BP) > 150 mm Hg systolic BP (SBP), or > 100 mm Hg diastolic BP (DBP) despite optimal antihypertensive treatment
  • Past history NYHA (New York Heart Association) class III or IV congestive heart failure
  • Thromboembolic event within 6 months before inclusion
  • current or past long-time smokers defined by more than 15 pack years
  • Second or third atrioventricular block
  • Active cancer
  • Past history of cancer the 5 years before the inclusion with the following exception:
  • -Patients with cervical carcinoma in situ that has been resected with no evidence of recurrence or metastatic disease for at least 3 years may participate in the study.
  • -Patients with basal cell or squamous epithelial skin cancers that have been completely resected with no evidence of recurrence for at least 3 years may participate in the study.
  • Have had symptomatic herpes zoster infection within 6 months prior to screening
  • Have a past history of recurrent symptomatic zona (one single symptomatic zona that had occurred more than 6 months before the inclusion is not a contra-indication)
  • Have a history of disseminated/complicated herpes zoster (for example, multidermatomal involvement, ophthalmic zoster, CNS involvement, or post-herpetic neuralgia).
  • Have been exposed to a live vaccine within 12 weeks prior to planned inclusion or are expected to need/receive a live vaccine during the course of the study (with the exception of herpes zoster vaccination that must occur > 4 weeks prior to inclusion).
  • Have active or chronic viral infection from hepatitis B virus (HBV, defined by positive aghbs), hepatitis C virus (HCV, defined by positive PCR), or human immunodeficiency virus (HIV, defined by positive serology).
  • Patients under guardianship (tutelle/curatelle)
  • Patient deprived of liberty under judicial or administrative decision.
  • Participation in another interventional trial
  • Hypersensitivity to the active substance (baricitinib) or to any of the excipients
  • Past history of organ transplantation
  • Surgery of the target IHCA required at diagnosis validated by a multidisciplinary tumor board during the screening process due to the following reason:
  • Male with HCA accessible to liver resection (male not accessible to surgery based on a multidisciplinary tumor board evaluation could be included)
  • Activation of the Wnt/B-catenin pathway at immunohistochemistry (diffuse positive glutamine synthase and/or nuclear translation of B-catenin) or mutations in exon 3 of CTNNB1 at molecular biology (except in this tumor is considered as unresectable) at the pathological reviewing
  • Signs of malignant transformation in HCC (suspected by multidisciplinary tumor board based on imaging features or results of histology)
  • Any other reasons validated by the multidisciplinary tumor board

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Ancillary study
PET CT with 18 FDG will be performed in 12 patients in selected centers (Avicenne hospital, Beaujon hospital, Henri Mondor hospital, Bordeaux hospital, Paul brousse hospital, Saint Antoine hospital with nuclear medicine department available and should be done at baseline and 3 months (+/- one week).
Drug: Baricitinib
An ancillary study will be performed in a subgroup of 12 patients to assess the variation of the results of PET-CT with 18FDG from baseline to 3 months. The variation of tumor features assessed by PET-CT with 18FDG after three months of treatment, will be assessed. The median value of the SUV max and tumor to non-tumor ratio of the SUV max value for each HCA lesion between the PET CT with 18FDG performed at baseline and after 3 months of treatment will be assessed.
Other Names:
  • fluorodésoxyglucose (18F)- Positron Emission Tomography (PET)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The principal outcome is to demonstrate that the combination of an experimental procedure to the standard of care lead to a significant decrease in size of large inflammatory HCA at imaging
Time Frame: 6 month
The primary endpoint will be assessed at 6 months by comparing the liver MRI with contrast agent at baseline with the liver MRI with contrast agent at 6 months. An external independent reviewing will be performed separately by two radiologists that will classify the radiological response according to RECIST 1.1 criteria at 6 months in complete response, partial response, stable disease and progressive disease.
6 month

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Radiological response using RECIST 1.1 and at 3 months and 6 months
Time Frame: 3 months and 6 months
Proportion of overall radiological response (partial and complete response), stable disease, and progressive disease using RECIST 1.1 criteria at 3 months and 6 months MRI
3 months and 6 months
Decrease in size of the target lesions below 5 cm at 3 months and 6 months at imaging using RECIST 1.1 criteria
Time Frame: 3 months and 6 months
Proportion of target lesions (inflammatory HCA > 5 cm) showing a decrease in size below 5 cm at 3 months and 6 months MRI using RECIST 1.1 thus modified RECIST criteria at MRI
3 months and 6 months
Need for liver surgery of HCA at 6 months and 24 months (end of the follow-up) due to absence of sufficient decrease in size of the tumor under baricitinib
Time Frame: 6 months and 24 months
Proportion patients treated by liver surgery for HCA at 6 months and the end of the 24 months follow-up
6 months and 24 months
Incidence of adverse events related to the experimental treatment (baracitinib)
Time Frame: Inclusion at 24 month
Adverse events within the 24 months of the study a) all adverse events b) occurrence of zona c) cancer d) major adverse cardiovascular events (MACE)
Inclusion at 24 month
In patients with multiple HCA, radiological response using RECIST 1.1 at 3 months and 6 months focusing of HCA at the exclusion of the IHCA confirmed at histology
Time Frame: 3 months and 6 months
In patients with multiple HCA, the proportion patients with complete response, partial response, stable disease and progressive disease focusing on other HCA excluding the inflammatory HCA confirmed at histology according to RECIST 1.1 criteria at MRI at 3 months and 6 months.
3 months and 6 months
Symptomatic HCA bleeding during follow-up
Time Frame: follow-up (D15, M1, M3, M6, M12; M18 and M24)
Proportion of symptomatic bleeding of HCA during follow-up
follow-up (D15, M1, M3, M6, M12; M18 and M24)
Incidence of malignant transformation of hepatocellular adenomas into hepatocellular carcinoma during the study
Time Frame: follow-up (D15, M1, M3, M6, M12; M18 and M24)
Proportion of malignant transformation in HCC during follow-up at histology and confirmed by a multidisciplinary tumor board
follow-up (D15, M1, M3, M6, M12; M18 and M24)
Occurrence of increase in tumor size or number after discontinuation of baricitinib using RECIST 1.1 criteria during follow-up
Time Frame: baricitinib discontinuation (6 months) to 24 months
Proportion of patients with a progressive disease between baricitinib discontinuation (6 months) and 24 months of follow-up using RECIST 1.1 criteria at imaging
baricitinib discontinuation (6 months) to 24 months
Occurrence of increase in tumor size up to 5 cm after discontinuation of baricitinib using RECIST 1.1 criteria during follow-up
Time Frame: baricitinib discontinuation (6 months) to 24 months
Proportion of patients with an increase in tumor size below 5 cm between baricitinib discontinuation (6 months) and 24 months at MRI
baricitinib discontinuation (6 months) to 24 months
Incidence of post-operative adverse events in cases requiring hepatic surgery for hepatocellular adenoma during follow-up
Time Frame: follow-up (D15, M1, M3, M6, M12; M18 and M24)
Proportion of post-operative adverse events (using the Dindo-Clavien Classification) if liver surgery is required during follow-up
follow-up (D15, M1, M3, M6, M12; M18 and M24)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Assistance Publique - Hôpitaux de Paris

Investigators

  • Principal Investigator: Jean-Charles NAULT, PUPH, Assistance Publique des Hôpitaux de Paris (APHP)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 2, 2024

Primary Completion (Estimated)

September 2, 2028

Study Completion (Estimated)

September 2, 2028

Study Registration Dates

First Submitted

June 24, 2024

First Submitted That Met QC Criteria

July 1, 2024

First Posted (Actual)

July 8, 2024

Study Record Updates

Last Update Posted (Actual)

December 26, 2025

Last Update Submitted That Met QC Criteria

December 19, 2025

Last Verified

October 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • APHP220916

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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