Overview
Sponsor-declared trial summary
Phase
Therapeutic confirmatory (Phase III)
Status
Authorised, recruitment pending
Participants planned
94
Countries
1
Sites
6
Cholestatic hepatitis induced by immune checkpoint inhibitors (ICIs)
Compare the effectiveness of ursodeoxycholic acid (UDCA) to corticosteroids in treating cholestatic hepatitis induced by immune checkpoint inhibitors (ICIs) over a 21-day period.
Key facts
- Sponsor
- Centre Hospitalier Universitaire De Montpellier
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Digestive System Diseases [C06], Diseases [C] - Neoplasms [C04]
- Decision date (initial)
- 2025-10-30
- Transition trial
- No
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- No
- Funding sources
- DGOS
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Therapy, Efficacy
Compare the effectiveness of ursodeoxycholic acid (UDCA) to corticosteroids in treating cholestatic hepatitis induced by immune checkpoint inhibitors (ICIs) over a 21-day period.
Secondary objectives 5
- To assess the efficacy in terms of hepatitis resolution at 6 months by treatment response group: • in patients responding to UDCA at day 21 • in patients responding to corticosteroids at day 21 • in patients who failed UDCA and after the addition of corticosteroids at day 21 • in patients who failed corticosteroids and after the addition of UDCA at day 21
- Assess time to resolution of hepatitis by treatment response group
- Evaluate the tolerance of UDCA, corticosteroids, and the combination of the two
- Determine predictive factors for response to UDCA at D21
- To assess the rate of ICI resumption by treatment response group
Conditions and MedDRA coding
Cholestatic hepatitis induced by immune checkpoint inhibitors (ICIs)
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 20.1 | LLT | 10008639 | Cholestatic hepatitis | 10019805 |
Study design 2 periods
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | Screening Screening and inclusion from J-10 to J0
|
Not Applicable | None | ||
| 2 | Randomisation & treatment Randomisation of patients into experimental or control arm and starting of treatment.
From J0 to J21
|
Randomised Controlled | None | Experimental arm: Patients in the experimental group will receive oral UDCA at an initial dose of 13-15 mg/kg twice daily. Control arm: Patients in the control group will receive corticosteroid therapy (standard treatment) at a dose of 0.5-1 mg/kg |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 4
- Adults, 18 years old with any type of cancer except hepatocellular or cholangiocarcinoma
- Any therapeutic line (adjuvant or palliative), at least one ICI injection
- cholestatic hepatitis R≤ 2 (R=ratio (ALT/ULN) /(PAL/ULN)) , Grade CTC-AE 3 or 4.
- Women of childbearing age using an appropriate contraceptive method throughout the entire duration of the treatment
Exclusion criteria 10
- Ongoing corticosteroids treatment
- other causes of hepatitis, cirrhosis
- ICI for hepatocellular carcinoma or cholangiocarcinoma
- biliary obstruction
- medical contraindication to corticosteroids or UDCA medical contraindication to MRI or liver biopsy
- mixed or hepatocellular hepatitis,
- total bilirubin > 1,5 ULN, prothrombin rate < 70%
- other serious side effects requiring corticosteroids
- patients under articles L1121-5 to 8 of the public health code, lack of informed consent, patients not affiliated with French social security system and patients uncapable of understanding/ reading/ writing in french
- Pregnant and breastfeeding patients
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- The rate of patients showing an improvement of at least 25% in liver function tests (alkaline phosphatase and/or gamma-GT) from baseline on Day 21.
Secondary endpoints 5
- Rate of patients with resolution of hepatitis, i.e., grade ≤ 1 according to the current NCI CTC-AE classification, at 6 months after randomization
- the time to hepatitis resolution (grade ≤ 1) defined as the time from the date of randomization to the date of resolution of hepatitis
- the tolerance to UDCA or corticosteroids or both: Adverse events assessed according to the current NCI-CTC AE classification
- Factors associated with response to UDCA at D21 among the immunotherapy molecule, duration of ICI treatment, presence or absence of bile duct dilation, tumor histology
- Rate of patients in whom resumption of immunotherapy was possible after hepatitis within 12 months after randomization
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
SCP10342130 · ATC
- Active substance
- Ursodeoxycholic Acid
- Substance synonyms
- URSODIOL, URSODESOXYCHOLIC ACID
- Route of administration
- ORAL USE
- Max daily dose
- 20 mg/kg milligram(s)/kilogram
- Max total dose
- 1000 mg milligram(s)
- Max treatment duration
- 6 Month(s)
- Authorisation status
- Authorised
- ATC code
- A05AA02 — URSODEOXYCHOLIC ACID
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Comparator 1
CORTANCYL 20 mg, comprimé sécable
PRD9995017 · Product
- Active substance
- Prednisone
- Pharmaceutical form
- TABLET
- Route of administration
- ORAL USE
- Max daily dose
- 1 mg/kg milligram(s)/kilogram
- Max total dose
- 1 mg/Kg milligram(s)/kilogram
- Max treatment duration
- 12 Week(s)
- Authorisation status
- Authorised
- ATC code
- H02AB07 — PREDNISONE
- Marketing authorisation
- 34009 332 838 5 8
- MA holder
- CHEPLAPHARM ARZNEIMITTEL GMBH
- MA country
- France
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Centre Hospitalier Universitaire De Montpellier
- Sponsor organisation
- Centre Hospitalier Universitaire De Montpellier
- Address
- 39 Avenue Charles Flahault
- City
- Montpellier Cedex 5
- Postcode
- 34295
- Country
- France
Scientific contact point
- Organisation
- Centre Hospitalier Universitaire De Montpellier
- Contact name
- MEUNIER
Public contact point
- Organisation
- Centre Hospitalier Universitaire De Montpellier
- Contact name
- Cadene
Locations
1 EU/EEA country · 6 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| France | Authorised, recruitment pending | 94 | 6 |
| Rest of world | — | 0 | — |
Investigational sites
Centre Hospitalier Universitaire De Bordeaux
HEPATOGASTROENTEROLOGIE, Avenue De Magellan, 33600, Pessac
Hospital La Croix Rousse Hcl
Hapatogastroenterologie, 103 Grande Rue De La Croix Rousse, 69317, Lyon Cedex 04
Centre Hospitalier Universitaire De Poitiers
hepatogastrenterologie, 2 Rue De La Miletrie, 86000, Poitiers
Centre Hospitalier Universitaire De Toulouse
IUCT oncopole, 1 Avenue Irene Joliot Curie, 31059, Toulouse Cedex 9
CHU Saint Eloi
Hepatogastroenterologie, 8 0Avnenue Augustin Fliche, 34295, Montpellier
Hopital Paul Brousse
Centre hapato-biliaire, 12 Avenue Paul Vaillant Couturier, 94804, Villejuif Cedex
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 8 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_ Protocol FP 2025-521317-50-00 | 1.2 |
| Recruitment arrangements (for publication) | K_Recruitment potentiel | 1 |
| Recruitment arrangements (for publication) | K1_Document additionnel | 1 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF participant | 1.2 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Cholurso | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Cortancyl | 1 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis 2025-521317-50-00 | 1.2 |
Application history
2 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2025-07-22 | France | Acceptable 2025-10-30
|
2025-10-30 |
| 2 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2025-11-17 | France | Acceptable 2025-10-30
|
2025-11-17 |