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

NCT06490757•Assistance Publique - Hôpitaux de Paris

Summary

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.

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.

Eligibility

Age

18 - 65 years

Sex

ALL

Healthy Volunteers

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
+1 more criteria

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
+36 more criteria

Locations (1)

NAULT

Bobigny, France

Key Dates

Start Date

October 2, 2024

Primary Completion Date

September 2, 2028

Completion Date

September 2, 2028

Last Updated

December 26, 2025

Enrollment

ESTIMATED participants

Conditions

Inflammatory Hepatocellular Adenoma

Interventions

Baricitinib

DRUG

Contacts

Jean Charles NAULT, PUPH

CONTACT

00336 10 67 94 61 jean-charles.nault@aphp.fr