Clinical trial · Interventional
Treatment Efficacy of Corticosteroids and Mycophenolate Mofetil in Patients With Immune Related Hepatitis
A National Prospective Study of Patients With Hepatitis Induced by Immune Checkpoint Inhibitors; Characterization of Liver Injury, Outcome of Therapy and Randomization to Either Prednisolone or Mycophenolate Mofetil Treatment in Case of Relapse
NCT04810156CI-TRIAL-00062694I-HEPunknownPhase 2ClinicalTrials.gov clinicaltrialsProvenance
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
This clinical trial is to clarify and investigate the patterns of immune-related hepatitis and the optimal treatment choice for patients who are steroid-dependent. The project aims to prospectively characterize the various histopathological, biochemical, and phenotypical liver injury patterns induced by immune checkpoint inhibitors and the treatment responses to corticosteroids. Furthermore, the effect of adding a second-line immunosuppressive drug, either MMF in steroid-refractory or steroid-dependent cases will be explored and compared.
Conditions
Conditions (1)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Hepatitis, Drug-Induced | — | UNRESOLVED | — |
Interventions
Interventions (4)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Mycophenolate Mofetil | Drug | — | UNRESOLVED |
| Prednisone tablet | Drug | Prednisone | ALIAS |
| Solu-Medrol | Drug | — | UNRESOLVED |
| Ursodeoxycholic acid | Drug | — | UNRESOLVED |
Design
Arms and outcomes
Arms (2)
- type
- ACTIVE_COMPARATOR
- label
- Cohort A: Steroids and MMF in grade 3-4 ir-hepatitis
- description
- Patients with ≥ 3 grade ir-hepatitis will be treated with high-dose steroids 2 mg/kg/day intravenously. A diagnostic liver biopsy will be taken. Patients with mixed or cholestatic liver injury patterns will be added UDCA. Treatment evaluation will be performed after 72 hours, patients in UDCA will be evaluated will be on day 7. Patients with sufficient steroid response defined as ≥ 20% reduction in ALT, AST, ALP or bilirubin at day 4 or day 7 will undergo steroid tapering with a transition to peroral steroids. Patients with initial insufficient treatment response, defined as less than \< 20% reduction in ALT, AST, ALP, or bilirubin, are considered as having a steroid-refractory condition and will be added MMF. In case of no response or increase of ALT, AST, ALP, or bilirubin during treatment with steroids plus MMF a third-line treatment may be introduced according to the individual treating hepatologist.
- interventionNames
- Drug: Mycophenolate Mofetil
- Drug: Solu-Medrol
- Drug: Ursodeoxycholic acid
- Drug: Prednisone tablet
- type
- ACTIVE_COMPARATOR
- label
- Cohort B: Prednisolone versus MMF in steroiddependent ≥2 ir-hepatitis (randomized)
- description
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
Inclusion Criteria: Cohort A: \- Abnormal liver parameters equal to ≥ grade 3 ir-hepatitis defined as; AST/ALT/ALP \>5 x ULN, INR ≥ 2.5 x ULN, or bilirubin \> 3.0 x ULN Cohort B: \- Patients who recur during or within one months of prednisolone tapering of ≥2 ir-hepatitis equal to AST/ALT ≥3 x ULN, ALP ≥2.5 x ULN, INR ≥ 1.5 x ULN, or bilirubin ≥ 3.0 x ULN Cohort A and Cohort B * Histologically confirmed solid cancer * Treatment with cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) or Programmed Cell Death-1 (PD-1)/Programmed Cell Death Ligand-1 (PD-L1) inhibitor or a combination of CTLA-4 plus PD-1 inhibitors within 6 months * Age: ≥ 18 years * Women of childbearing potential: Negative serum pregnancy test and must use effective contraception. This applies from screening and until 6 months after treatment. Birth control pills, spiral, depot injection with gestagen, subdermal implantation, hormonal vaginal ring and transdermal depot patch are all considered effective contraceptives * Men with female partner of childbearing potential must use effective contraception from screening and until 6 months after treatment. Effective contraceptives are as described above for the female partner. In addition, documented vasectomy and sterility or double barrier contraception are considered effective contraceptives * Signed statement of consent after receiving oral and written study information * Willingness to participate in the planned treatment and follow-up and capable of handling toxicities. Exclusion Criteria: * Concomitant chemotherapy treatment or tyrosine kinases or angiogenesis inhibitors * Concomitant immunosuppressive medication except prednisolone * Patients with hepatocellular carcinoma * Known hypersensitivity to one of the active drugs or excipients * Uncontrolled infection * Acute viral hepatitis * Any medical condition that will interfere with patient compliance or safety * Simultaneous treatment with other experimental drugs or other anticancer drugs * Pregnant or breastfeeding females * Phenylketonuria
References
Publications (1)
- DERIVEDHolmstroem RB, Teisner AS, Sweep MWD, Noringriis IM, Khan S, Aagaard NK, Karlstrom J, Jurlander RS, Sohlin JE, Monberg TJ, Vestergaard C, Stoltenborg Granhoj J, Stenbog P, Toxvaerd A, Hansen AB, Bjerring PN, Lorentzen T, Thielsen P, Bol K, Jonsson G, Ellebaek E, Svane IM. Prospective study of patients with immune checkpoint inhibitor-induced hepatitis; characterization of liver injury, outcome of therapy, and management of steroid-unresponsive and steroid-dependent hepatitis. J Immunother Cancer. 2026 Mar 5;14(3):e013861. doi: 10.1136/jitc-2025-013861. PMID 41786454