Efficacy and safety of prednisone in the treatment of idiosyncratic hepatotoxicity

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fundacion Publica Andaluza Para La Investigacion De Malaga En Biomedicina Y Salud

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

14 Jan 2025 → ongoing

Decision date (initial)

2024-07-15

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To assess if oral prednisone (compared to placebo), administered over five weeks is beneficial in terms of decreased TBL, i.e., reduction of the peak of TBL by at least 50% at 14 days or reduction time to normalisation of TBL value.
To assess if oral prednisone (compared to placebo) is safe and well tolerated in patients with acute moderate to severe DILI.

Secondary objectives 3

1. To assess if oral prednisone (compared to placebo), administered for five weeks, is beneficial in reducing peak alanine aminotransferase (ALT), aspartate aminotransferase (AST) and international normalized ratio (INR) values by at least 50% at day 7 or reducing the time to normalisation.
2. To assess if oral prednisone (compared to placebo), decreases the proportion of patients that evolve to acute liver failure.
3. To evaluate changes in health-related quality of life if oral prednisone (compared to placebo).

Conditions and MedDRA coding

Hepatotoxicity

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Female and male patients, aged ≥ 18 years
2. Patients who have been diagnosed with DILI by the expert committee
3. Patients with moderate to severe DILI (elevations of ALT or AST ≥ 5 x ULN and serum TBL ≥ 2.5 mg/dL.
4. Patients who do not show a 15% reduction in ALT values or TBL continues to increase 5-10 days after liver damage recognition despite the withdrawal of the culprit drug.

Exclusion criteria 11

1. No clear DILI diagnosis after an expert committee DILI assessment.
2. DILI due to immune-checkpoint inhibitors
3. Presence of active infection as evidenced by positive urine or blood culture.
4. Acute liver failure (INR > 1.5 and hepatic encephalopathy)
5. Model for End-Stage Liver Disease (MELD) ≥ 30.
6. Known hypersensitivity to prednisone or placebo components
7. Pregnant or nursing mothers
8. Co-existing infection with hepatitis C, hepatitis B, or HIV
9. Patients already receiving systemic steroids or other immunosuppressants
10. Inability to provide informed consent
11. Presence of clinically significant comorbid illnesses (by clinician’s criteria) that might impede completion of the study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. The proportion of patients that achieve a decrease of at least 50% of the peak value in TBL at day 14.
2. Time (days) to TBL value return to normal.
3. Proportion of AEs, SAEs, fatality, and proportion of patients with premature termination due to AEs.

Secondary endpoints 4

1. The proportion of patients that achieve a decrease of at least 50% of the peak value in ALT, AST and INR at day 7.
2. Time (days) for the ALT, AST and INR values return to normal.
3. Proportion of patients that develop acute liver failure, need for liver transplantation or liver related death at day 28.
4. Score changes in SF-36 quality of life validated questionnaire performed at visit 1 (day 1, start of treatment) and at visit 6 (day 35, end of treatment).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fundacion Publica Andaluza Para La Investigacion De Malaga En Biomedicina Y Salud

Sponsor organisation

Fundacion Publica Andaluza Para La Investigacion De Malaga En Biomedicina Y Salud

Address

Calle De Severo Ochoa 35, Parque Tecnologico De Andalucia Parque Tecnologico De Andalucia

City

Malaga

Postcode

29590

Country

Spain

Scientific contact point

Organisation

Fundacion Publica Andaluza Para La Investigacion De Malaga En Biomedicina Y Salud

Contact name

Rocío Moreno González and Elvira Bonilla Toyos

Public contact point

Organisation

Fundacion Publica Andaluza Para La Investigacion De Malaga En Biomedicina Y Salud

Contact name

Rocío Moreno González and Elvira Bonilla Toyos

Locations

1 EU/EEA country · 15 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 6 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications