Autoimmune HepatitisPhase 2/3NCT06650124
Induction of Remission in Autoimmune Hepatitis With Azathioprine vs. MMF
A Phase 2/3 study testing Mycophenolate Mofetil + Prednisolone Participants will receive mycophenolate mofetil in combination. and Azathioprine + Prednisolone in people with Autoimmune Hepatitis, run by Institute of Liver and Biliary Sciences, India.
Trial summary
The goal of this clinical trial is to determine the effectiveness of azathioprine (AZA) versus mycophenolate mofetil (MMF) in inducing remission in treatment-naive patients with autoimmune hepatitis (AIH). Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Autoimmune Hepatitis
- What is being tested?
- Mycophenolate Mofetil + Prednisolone Participants will receive mycophenolate mofetil in combination. and Azathioprine + Prednisolone
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 108 participants
- Where
- No sites listed yet
- Study dates
- 1 Nov 2024to 31 Dec 2025
- Phase
- Phase 2/3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis: Confirmed diagnosis of autoimmune hepatitis (AIH) based on clinical, biochemical, and histological findings.
- Biochemical markers: Elevated liver enzymes, specifically AST and ALT, indicating liver inflammation.
- Treatment-naive: Patients must be treatment-naive, meaning they have not received prior immunosuppressive therapy for AIH.
- Willingness to participate: Patients must provide informed consent and be willing to comply with all study-related procedures and follow-ups. -
Who cannot join
- Acute liver failure: Patients presenting with acute liver failure at baseline will be excluded.
- Other liver diseases: Co-existing liver conditions such as hepatitis B, hepatitis C, primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), or any alcohol-induced liver disease will lead to exclusion.
- Low blood counts: Patients with a platelet count less than 50,000/mm³ or total leukocyte count (TLC) less than 3,000/mm³ will not be eligible.
- Previous treatment: Patients who have already received immunosuppressive or disease-modifying therapy for AIH or related conditions.
- Pregnancy or lactation: Pregnant or lactating women will be excluded to avoid potential risks to the mother or fetus.
- Hepatocellular carcinoma (HCC) or malignancy: Any patients with evidence of hepatocellular carcinoma or other active malignancies.
- Medication allergies: Patients with known allergies to azathioprine, mycophenolate mofetil (MMF), or prednisolone will be excluded.
- Non-consent: Patients who are not willing to participate in the study or unable to provide informed consent.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
The goal of this clinical trial is to determine the effectiveness of azathioprine (AZA) versus mycophenolate mofetil (MMF) in inducing remission in treatment-naive patients with autoimmune hepatitis (AIH). The main questions it aims to answer are:
Does MMF combined with prednisolone lead to higher remission rates compared to AZA with prednisolone after 24 weeks? Is MMF associated with fewer adverse events than AZA in these patients? Researchers will compare two treatment arms (MMF vs. AZA) to see if MMF leads to improved remission rates and safety outcomes.
Read more
Primary Outcome Measure:
Biochemical remission: The primary outcome is the normalization of liver enzymes (AST, ALT) and IgG levels at 24 weeks.
Secondary Outcome Measures:
Safety and adverse events: Monitoring and comparing the incidence and severity of side effects between the two groups.
Treatment adherence: Evaluating how well patients stick to their assigned treatment regimens.
Improvement in quality of life: Assessing changes in the patient's quality of life using validated questionnaires.
Reversal of fibrosis: Measured by liver stiffness using Fibroscan, aiming for no progression of fibrosis.
Participants will:
Receive either MMF or AZA, alongside a tapering dose of prednisolone. Be monitored regularly through clinic visits, laboratory tests, and safety assessments to track remission and any adverse events.
Read the detailed description
This clinical trial aims to compare the efficacy and safety of azathioprine (AZA) versus mycophenolate mofetil (MMF) in inducing remission in treatment-naive patients with autoimmune hepatitis (AIH). Autoimmune hepatitis is a chronic liver disease characterized by immune-mediated liver inflammation, leading to liver damage, cirrhosis, or liver failure if untreated.
The study will be conducted at the Institute of Liver and Biliary Sciences (ILBS), where eligible patients with AIH will be randomly assigned to one of two treatment groups:
AZA Group: Patients will receive azathioprine at an initial dose of 50 mg/day, increased to 100 mg/day after two weeks, combined with a tapering dose of prednisolone.
MMF Group: Patients will receive mycophenolate mofetil at an initial dose of 1,000 mg/day, increased to 2,000 mg/day after two weeks, along with a tapering dose of prednisolone.
The trial will enroll 108 patients and follow a double-blind, randomized controlled design. The primary endpoint is achieving biochemical remission within 24 weeks, defined by normalizing liver enzymes (AST, ALT) and IgG levels. Secondary endpoints include safety, tolerability, treatment adherence, quality of life, and the prevention or reversal of liver fibrosis (as measured by Fibroscan).
The trial's expected duration is one year, with follow-up visits every 4 weeks to monitor patient progress and adverse events. All necessary tests and treatments will follow institutional protocols without additional cost to participants.
This study is essential to address the current gaps in AIH treatment, offering critical evidence to guide future clinical decisions on the use of MMF versus AZA for remission induction in AIH.
- Conditions
- Autoimmune Hepatitis
- Being tested
- Mycophenolate Mofetil + Prednisolone Participants will receive mycophenolate mofetil in combination., Azathioprine + Prednisolone
- Keywords
- utoimmune Hepatitis (AIH), Azathioprine (AZA), Mycophenolate Mofetil (MMF), Induction of Remission
- Medical subject headings
- Hepatitis, Autoimmune
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Mycophenolate Mofetil + Prednisolone Participants will receive mycophenolate mofetil in combination.Drug
Participants in this arm will receive mycophenolate mofetil (MMF) starting at 1,000 mg/day for the first two weeks, increasing to 2,000 mg/day thereafter. This will be combined with prednisolone, beginning at 40-60 mg/day, with a tapering dose to 5-10 mg/day after 4-8 weeks, depending on the patient's response. MMF works by inhibiting inosine monophosphate dehydrogenase, which decreases lymphocyte proliferation, thereby reducing immune-mediated liver damage in autoimmune hepatitis. Prednisolone, a corticosteroid, is included to control inflammation during the induction phase of treatment. This intervention lasts for 24 weeks, with monitoring for biochemical remission (normalization of liver enzymes and IgG levels) and adverse events to assess the treatment's safety and efficacy.
Azathioprine + PrednisoloneDrug
In this arm, participants will receive azathioprine (AZA) starting at 50 mg/day for the first two weeks, followed by an increase to 100 mg/day. This dose will be combined with prednisolone, starting at 40-60 mg/day, with the dosage tapering to 5-10 mg/day after 4-8 weeks, depending on patient response. Azathioprine works as an immunosuppressive agent by inhibiting DNA synthesis in rapidly dividing immune cells, thereby reducing liver inflammation in autoimmune hepatitis. Prednisolone, a corticosteroid, is included to control inflammation during the initial treatment phase. The intervention lasts for 24 weeks with regular monitoring for biochemical remission, defined as normalization of liver enzymes (AST, ALT) and IgG levels, as well as the occurrence of adverse events to assess safety and tolerability.
| Study group | Role | What they receive |
|---|---|---|
| Azathioprine + Prednisolone Arm | Active comparator | Azathioprine + Prednisolone Arm Participants will receive azathioprine (AZA) in combination with prednisolone as part of their treatment regimen. Receives: Drug: Azathioprine + Prednisolone |
| Mycophenolate Mofetil + Prednisolone Arm | Active comparator | Mycophenolate Mofetil + Prednisolone Arm Participants will receive mycophenolate mofetil (MMF) in combination with prednisolone as part of their treatment regimen. Receives: Drug: Mycophenolate Mofetil + Prednisolone Participants will receive mycophenolate mofetil in combination. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Biochemical Remission at 24 Weeks
Definition: Normalization of liver enzymes (ALT, AST) and immunoglobulin G (IgG) levels.
Time Frame: Measured at 24 weeks of treatment. Purpose: To evaluate the effectiveness of mycophenolate mofetil (MMF) versus azathioprine (AZA) in achieving biochemical remission in treatment-naive autoimmune hepatitis (AIH) patients.
Measured: 24 weeks
Secondary outcomes (4)
Incidence and Severity of Adverse Events
Definition: Number and severity (mild, moderate, or severe) of adverse events related to the treatment.
Time Frame: Assessed at each follow-up visit (every 4 weeks) during the 24-week treatment period.
Purpose: To compare the safety profiles of MMF and AZA.
Measured: 24 weeks.
Treatment Adherence
Definition: Percentage of participants who complete the 24-week treatment without discontinuation due to adverse events or non-compliance.
Time Frame: Measured throughout the 24-week period. Purpose: To assess patient adherence to treatment protocols in both groups.
Measured: 24 weeks.
Quality of Life Improvement
Definition: Change in the quality of life score based on a validated patient-reported outcome questionnaire, SF-36, and CLDQ.
Time Frame: Measured at baseline and 24 weeks. Purpose: To determine whether improvements in liver function correlate with better quality of life
Measured: 24 weeks.
Change in Liver Fibrosis
Definition: Change in liver fibrosis stage, measured by Fibroscan. Time Frame: Measured at baseline and 24 weeks. Purpose: To evaluate if either treatment leads to a reduction in liver fibrosis or prevents its progression.
Measured: 24 weeks.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Oct 2024
- Study start1 Nov 2024 (estimated)
- Primary completion31 Dec 2025 (estimated)
- Study completion31 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Autoimmune HepatitisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- nterventional Study Model: Parallel Assignment Study Type: Interventional (Clinical Trial) Study Model: Parallel Assignment - Participants are randomly assigned to one of two groups (either receiving azathioprine or mycophenolate mofetil) and remain in their assigned group for the entire study. Masking: Double-blind (both participants and investigators are unaware of which treatment is being administered to prevent bias). Allocation: Randomized - Patients are randomly allocated to one of the two treatment groups.
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 108 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Institute of Liver and Biliary Sciences, India
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06650124
- Sponsor's protocol ID
- 12/8/2023-ACAD/E-12745/992
- Status last verified
- Oct 2024
- First submitted
- 17 Oct 2024
- Last updated
- 7 Nov 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Investigators currently do not plan to share individual participant data (IPD) from this study. The decision is based on considerations of patient privacy, confidentiality concerns, and the lack of a data-sharing infrastructure. While the aggregated study results will be published and made publicly available, sharing individual-level data could pose risks related to identifying participants. Therefore, IPD will not be shared beyond what is required for regulatory purposes.
Publications
Snijders RJALM, Stoelinga AEC, Gevers TJG, Pape S, Biewenga M, Tushuizen ME, Verdonk RC, de Jonge HJM, Vrolijk JM, Bakker SF, Vanwolleghem T, de Boer YS, Baven Pronk MAMC, Beuers U, van der Meer AJ, Gerven NMFV, Sijtsma MGM, van Eijck BC, van IJzendoorn MC, van Herwaarden M, van den Brand FF, Korkmaz KS, van den Berg AP, Guichelaar MMJ, Levens AD, van Hoek B, Drenth JPH; Dutch Autoimmune Hepatitis Working Group. An open-label randomised-controlled trial of azathioprine vs. mycophenolate mofetil for the induction of remission in treatment-naive autoimmune hepatitis. J Hepatol. 2024 Apr;80(4):576-585. doi: 10.1016/j.jhep.2023.11.032. Epub 2023 Dec 14.
PubMed 38101756Santiago P, Schwartz I, Tamariz L, Levy C. Systematic review with meta-analysis: mycophenolate mofetil as a second-line therapy for autoimmune hepatitis. Aliment Pharmacol Ther. 2019 Apr;49(7):830-839. doi: 10.1111/apt.15157. Epub 2019 Feb 13.
PubMed 30761563Manns MP, Woynarowski M, Kreisel W, Lurie Y, Rust C, Zuckerman E, Bahr MJ, Gunther R, Hultcrantz RW, Spengler U, Lohse AW, Szalay F, Farkkila M, Prols M, Strassburg CP; European AIH-BUC-Study Group. Budesonide induces remission more effectively than prednisone in a controlled trial of patients with autoimmune hepatitis. Gastroenterology. 2010 Oct;139(4):1198-206. doi: 10.1053/j.gastro.2010.06.046. Epub 2010 Jun 22.
PubMed 20600032Manns MP, Czaja AJ, Gorham JD, Krawitt EL, Mieli-Vergani G, Vergani D, Vierling JM; American Association for the Study of Liver Diseases. Diagnosis and management of autoimmune hepatitis. Hepatology. 2010 Jun;51(6):2193-213. doi: 10.1002/hep.23584. No abstract available.
PubMed 20513004Czaja AJ. Current and future treatments of autoimmune hepatitis. Expert Rev Gastroenterol Hepatol. 2009 Jun;3(3):269-91. doi: 10.1586/egh.09.15.
PubMed 19485809Terziroli Beretta-Piccoli B, Mieli-Vergani G, Vergani D. Autoimmune hepatitis: Standard treatment and systematic review of alternative treatments. World J Gastroenterol. 2017 Sep 7;23(33):6030-6048. doi: 10.3748/wjg.v23.i33.6030.
PubMed 28970719Sarin SK, Kumar M, Lau GK, Abbas Z, Chan HL, Chen CJ, Chen DS, Chen HL, Chen PJ, Chien RN, Dokmeci AK, Gane E, Hou JL, Jafri W, Jia J, Kim JH, Lai CL, Lee HC, Lim SG, Liu CJ, Locarnini S, Al Mahtab M, Mohamed R, Omata M, Park J, Piratvisuth T, Sharma BC, Sollano J, Wang FS, Wei L, Yuen MF, Zheng SS, Kao JH. Asian-Pacific clinical practice guidelines on the management of hepatitis B: a 2015 update. Hepatol Int. 2016 Jan;10(1):1-98. doi: 10.1007/s12072-015-9675-4. Epub 2015 Nov 13.
PubMed 26563120Makol A, Watt KD, Chowdhary VR. Autoimmune hepatitis: a review of current diagnosis and treatment. Hepat Res Treat. 2011;2011:390916. doi: 10.1155/2011/390916. Epub 2011 May 15.
PubMed 21760995Czaja AJ, Freese DK; American Association for the Study of Liver Disease. Diagnosis and treatment of autoimmune hepatitis. Hepatology. 2002 Aug;36(2):479-97. doi: 10.1053/jhep.2002.34944. No abstract available.
PubMed 12143059