Autoimmune HepatitisPhase 4TAILORNCT05221411
Tacrolimus Versus Mycophenolate for Autoimmune Hepatitis Patients With Incomplete Response on First Line Therapy
A Phase 4 study testing Mycophenolate Mofetil and Tacrolimus in people with Autoimmune Hepatitis, run by Leiden University Medical Center at 6 sites in Netherlands.
Trial summary
Rationale: The combination of azathioprine and prednisone is the first-line treatment for autoimmune hepatitis (AIH), a chronic inflammatory disease of the liver. Complete biochemical remission (CR) is the first treatment goal in autoimmune hepatitis. CR is determined by AST and ALT and IgG within the reference range. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Autoimmune Hepatitis
- What is being tested?
- Mycophenolate Mofetil and Tacrolimus
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 86 participants
- Where
- 6 sitesNetherlands
- Study dates
- 19 Jan 2022to Jan 2024
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patient is older than 18 years old
- Probable or definite auto immune hepatitis according to the original or simplified IAIHG criteria (>10 points pre-treatment on the original criteria or >6 points on the simplified criteria)(2, 3)
- Incomplete responder on at least a half year of first-line treatment, with at least last 6 months azathioprine / 6-MP) / 6-TG and prednisolone or budesonide, and ALT 1.5 - 10x ULN for at least 2 months
- Patient is capable of understanding the purpose and risks of the study, has been fully informed and has given written informed consent to participate in the study
Who cannot join
- Presence of decompensated liver disease, defined as ascites, coagulopathy (INR >1.5), encephalopathy, variceal bleed, hepatopulmonal syndrome, hepatorenal syndrome or HCC in the past 6 months
- Signs of other liver diseases as NAFLD, Wilson disease, hemochromatosis, alcoholic liver disease or hepatitis B/C/D
- Clinical diagnosis of overlap / variant syndrome with PBC or PSC
- Liver transplantation in the medical history or currently on the waiting list for liver transplantation
- Incompliance with therapy during the last 12 months
- Active infections during inclusion including latent tuberculosis and HIV co-infection
Show all 11Show fewer
- Allergic or hypersensitive to tacrolimus or MMF
- An estimated glomerular filtration rate (eGFR) of <60 mL/min
- Pregnancy or intention to become pregnant in the next 12 months
- Use of TAC or MMF in the past
- Malignancy in the medical history
Trial locations and contacts
6 sites in 1 country.
Bart van Hoek contact
6 sites in 1 country
Netherlands6 sites, 6 recruiting
- Not yet recruiting
Jeroen Bosch Ziekenhuis
's-Hertogenbosch
Henk-Marijn de Jonge
- Not yet recruiting
Reinier de Graaf Gasthuis
Delft
Hans Brouwer
- Not yet recruiting
Medisch Spectrum Twente
Enschede
Maureen Guichelaar
- Recruiting
Leiden University Medical Center
Leiden
Bart van Hoek
- Not yet recruiting
Maastricht University Medical Center +
Maastricht
Tom Gevers
- Not yet recruiting
University Medical Center Utrecht
Utrecht
Suzanne van der Meer
About this study
Official title: TAILOR Study: Tacrolimus Versus Mycophenolate for Autolmmune Hepatitis Patients With incompLete Response On First Line Therapy: a Randomized Trial
Rationale: The combination of azathioprine and prednisone is the first-line treatment for autoimmune hepatitis (AIH), a chronic inflammatory disease of the liver. Complete biochemical remission (CR) is the first treatment goal in autoimmune hepatitis. CR is determined by AST and ALT and IgG within the reference range. CR is not reached in a substantial proportion of AIH patients: after one year 50%, after three years around 20% did not achieve CR. Without CR ongoing hepatitis leads to progression towards fibrosis and eventually (decompensated) cirrhosis. Not achieving CR is the most important risk factor for the need for liver transplantation or liver related death, independent of age and presence of cirrhosis. Tacrolimus (TAC) and mycophenolate mofetil (MMF) are frequently used to prevent rejection in kidney and liver transplant patients. In AIH patients with insufficient response or intolerance to first-line therapy in retrospective cohort studies with MMF 0-57% and with TAC 20-95% CR was reached.
Objective: The aim of this study is to compare the effectiveness of TAC with MMF as a second line treatment for AIH. Proportion of patients with CR after 12 months of treatment will be the primary outcome parameter to determine effectivity.
Read more
Study design: Randomized open-label two arm study. Patients will be randomized between treatment with TAC or MMF.
Study population: Patients with AIH with an incomplete response (no CR) to first-line treatment are eligible for this study.
Intervention: In the TAC group baseline treatment will be replaced by tacrolimus. In the MMF group baseline treatment will be replaced by MMF. The current dose of prednisolone, or at least 5 mg daily, will be continued in both arms. After achieving CR prednisolone will be tapered according to protocol.
Main study parameters/endpoints: Difference in proportion of patients with CR at 12 months (normalization of ALT, AST and IgG) between the TAC and MMF treatment group.
Secondary parameters:
- Safety and tolerability of TAC and MMF treatments
- Difference in proportion of patients with CR at 6 months (normalization of ALT, AST and IgG) between the TAC and MMF treatment group.
- Difference in ALT, AST and IgG at 6 and 12 months versus baseline
- Difference in fibrogenesis and fibrosis parameters between groups and before and after treatment
- Difference in quality of life between groups and before and after treatment
- Conditions
- Autoimmune Hepatitis
- Being tested
- Mycophenolate Mofetil, Tacrolimus
- Medical subject headings
- Hepatitis, Autoimmune
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Also called Cellcept
Mycophenolate mofetil will be started at a dose 500mg twice daily. When tolerated and an AUC within range, patients will be titrated to 1000mg twice daily at week two.
TacrolimusDrug
Also called Envarsus
Meltdose tacrolimus will be started at a dose of 0.07 mg/kg/day. The drug will be taken orally once-daily in the morning. Dose will be adjusted to reach target AUC and trough levels.
| Study group | Role | What they receive |
|---|---|---|
| Mycofenolate Mofetil | Experimental | Patients in the mycophenolate mofetil (MMF) arm will receive MMF for a total of 12 months (if tolerated) Receives: Drug: Mycophenolate Mofetil |
| Tacrolimus (Envarsus) | Experimental | Patients in the tacrolimus (TAC) arm will receive treatment with meltdose TAC for a total of 12 months (if tolerated) Receives: Drug: Tacrolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete biochemical remission
The proportion of patients with CR after 12 months of treatment with TAC compared to MMF in patients with AIH with an incomplete response to first-line treatment.
Measured: 52 weeks
Secondary outcomes (15)
Safety and Tolerability
Number and severity of side effects; Rate of stopping treatment due to side effects; serum creatinin \& potassium; Blood pressure; Blood glucose levels and incidence of new onset diabetes; Number of (opportunistic) infections; tremor; diarrhea
Measured: 52 weeks
Proportion of patients with complete biochemical remission after 6 months
Defined as ALT, AST and IgG below the upper limit of normal
Measured: 24 weeks
Proportion of patients with partial response
defined as decrease of AST and ALT, but no normalization
Measured: 52 weeks
Proportion of patients with insufficient treatment response
less than 25% reduction in ALT after 6 and 12 months treatment
Measured: 52 weeks
Dose reduction of prednisone
Difference between dose at inclusion and dose at the end of study
Measured: 52 weeks
Cessation rate of prednisone
The number of patients able to completely withdraw from corticosteroids
Measured: 52 weeks
Change of AST
at 6 and 12 months versus baseline and between groups at the same time points
Measured: 24 and 52 weeks
Change of ALT
at 6 and 12 months versus baseline and between groups at the same time points
Measured: 24 and 52 weeks
Change of IgG
at 6 and 12 months versus baseline and between groups at the same time points
Measured: 24 and 52 weeks
Liver function
Total bilirubin, albumin, INR and MELD-score after 6 and 12 months between groups
Measured: 24 and 52 weeks
Fibrosis
Liver stiffness as measured by elastography and blood fibrosis markers (ELF)
Measured: 52 weeks
Influence of liver disease on the quality of life
using the validated liver disease symptom index (LDSI)
Measured: 52 weeks
Treatment effect on health status
using the validated EQ5D
Measured: 52 weeks
Cost-effectiveness based on empiric data obtained by this study.
Economic evaluation including a cost-effectiveness evaluation
Measured: 52 weeks
Cost-effectiveness from a societal perspective
Economic evaluation including a cost-utility evaluation (costs per QALY)
Measured: 52 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Feb 2022
- Study start19 Jan 2022
- Primary completionJan 2023 (estimated)
- Study completionJan 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Autoimmune HepatitisStudies of the same condition, open and under way.
- More trials run by Leiden University Medical CenterThe sponsor's other registered studies.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 86 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Leiden University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Bart van Hoek, Leiden University Medical Center
- Investigators
- Bart van Hoek, Principal investigator, Leiden University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05221411
- Sponsor's protocol ID
- P21.089
- Other IDs
- 2021-003420-33, NL78216.058.21
- Acronym
- TAILOR
- Status last verified
- Jan 2022
- First submitted
- 7 Jan 2022
- Last updated
- 3 Feb 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Stoelinga AEC, Tushuizen ME, van den Hout WB, Girondo MDMR, de Vries ES, Levens AD, Moes DAR, Gevers TJG, van der Meer S, Brouwer HT, de Jonge HJM, de Boer YS, Beuers UHW, van der Meer AJ, van den Berg AP, Guichelaar MMJ, Drenth JPH, van Hoek B; Dutch Autoimmune Hepatitis Group. Tacrolimus versus mycophenolate for AutoImmune hepatitis patients with incompLete response On first-line therapy (TAILOR study): a study protocol for a phase III, open-label, multicentre, randomised controlled trial. Trials. 2024 Jan 17;25(1):61. doi: 10.1186/s13063-023-07832-w.
PubMed 38233878
Study at a glance
From the registry record, last updated by the sponsor on 3 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- TAILOR Study: Tacrolimus Versus Mycophenolate for Autolmmune Hepatitis Patients With incompLete Response On First Line Therapy: a Randomized Trial
- ClinicalTrials.gov ID
- NCT05221411
- Acronym / sponsor ID
- TAILOR / P21.089
- Conditions
- Autoimmune Hepatitis
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 86 participants (estimated)
- Lead sponsor
- Leiden University Medical CenterUniversity, hospital or other
- Study start
- 19 Jan 2022 (actual)
- Primary completion
- Jan 2023 (estimated)
- Study completion
- Jan 2024 (estimated)
- First posted
- 3 Feb 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Rationale: The combination of azathioprine and prednisone is the first-line treatment for autoimmune hepatitis (AIH), a chronic inflammatory disease of the liver. Complete biochemical remission (CR) is the first treatment goal in autoimmune hepatitis. CR is determined by AST and ALT and IgG within the reference range. CR is not reached in a substantial proportion of AIH patients: after one year 50%, after three years around 20% did not achieve CR. Without CR ongoing hepatitis leads to progression towards fibrosis and eventually (decompensated) cirrhosis. Not achieving CR is the most important risk factor for the need for liver transplantation or liver related death, independent of age and presence of cirrhosis. Tacrolimus (TAC) and mycophenolate mofetil (MMF) are frequently used to prevent rejection in kidney and liver transplant patients. In AIH patients with insufficient response or intolerance to first-line therapy in retrospective cohort studies with MMF 0-57% and with TAC 20-95% CR was reached.
Objective: The aim of this study is to compare the effectiveness of TAC with MMF as a second line treatment for AIH. Proportion of patients with CR after 12 months of treatment will be the primary outcome parameter to determine effectivity.
Study design: Randomized open-label two arm study. Patients will be randomized between treatment with TAC or MMF.
Study population: Patients with AIH with an incomplete response (no CR) to first-line treatment are eligible for this study.
Intervention: In the TAC group baseline treatment will be replaced by tacrolimus. In the MMF group baseline treatment will be replaced by MMF. The current dose of prednisolone, or at least 5 mg daily, will be continued in both arms. After achieving CR prednisolone will be tapered according to protocol.
Main study parameters/endpoints: Difference in proportion of patients with CR at 12 months (normalization of ALT, AST and IgG) between the TAC and MMF treatment group.
Secondary parameters:
- Safety and tolerability of TAC and MMF treatments
- Difference in proportion of patients with CR at 6 months (normalization of ALT, AST and IgG) between the TAC and MMF treatment group.
- Difference in ALT, AST and IgG at 6 and 12 months versus baseline
- Difference in fibrogenesis and fibrosis parameters between groups and before and after treatment
- Difference in quality of life between groups and before and after treatment
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Mycofenolate Mofetil | Experimental | Drug: Mycophenolate MofetilPatients in the mycophenolate mofetil (MMF) arm will receive MMF for a total of 12 months (if tolerated) |
| Tacrolimus (Envarsus) | Experimental | Drug: TacrolimusPatients in the tacrolimus (TAC) arm will receive treatment with meltdose TAC for a total of 12 months (if tolerated) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Patient is older than 18 years old
- Probable or definite auto immune hepatitis according to the original or simplified IAIHG criteria (>10 points pre-treatment on the original criteria or >6 points on the simplified criteria)(2, 3)
- Incomplete responder on at least a half year of first-line treatment, with at least last 6 months azathioprine / 6-MP) / 6-TG and prednisolone or budesonide, and ALT 1.5 - 10x ULN for at least 2 months
- Patient is capable of understanding the purpose and risks of the study, has been fully informed and has given written informed consent to participate in the study
Key exclusion criteria (11 listed)
- Presence of decompensated liver disease, defined as ascites, coagulopathy (INR >1.5), encephalopathy, variceal bleed, hepatopulmonal syndrome, hepatorenal syndrome or HCC in the past 6 months
- Signs of other liver diseases as NAFLD, Wilson disease, hemochromatosis, alcoholic liver disease or hepatitis B/C/D
- Clinical diagnosis of overlap / variant syndrome with PBC or PSC
- Liver transplantation in the medical history or currently on the waiting list for liver transplantation
- Incompliance with therapy during the last 12 months
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Mycophenolate MofetilAlso: CellceptMycophenolate mofetil will be started at a dose 500mg twice daily. When tolerated and an AUC within range, patients will be titrated to 1000mg twice daily at week two. | Drug | Mycofenolate Mofetil |
| TacrolimusAlso: EnvarsusMeltdose tacrolimus will be started at a dose of 0.07 mg/kg/day. The drug will be taken orally once-daily in the morning. Dose will be adjusted to reach target AUC and trough levels. | Drug | Tacrolimus (Envarsus) |
Primary outcome
Complete biochemical remission
Time frame: 52 weeks
The proportion of patients with CR after 12 months of treatment with TAC compared to MMF in patients with AIH with an incomplete response to first-line treatment.
15 secondary outcomes
Safety and Tolerability
Time frame: 52 weeks
Proportion of patients with complete biochemical remission after 6 months
Time frame: 24 weeks
Proportion of patients with partial response
Time frame: 52 weeks
Proportion of patients with insufficient treatment response
Time frame: 52 weeks
Dose reduction of prednisone
Time frame: 52 weeks
Cessation rate of prednisone
Time frame: 52 weeks
Change of AST
Time frame: 24 and 52 weeks
Change of ALT
Time frame: 24 and 52 weeks
Change of IgG
Time frame: 24 and 52 weeks
Liver function
Time frame: 24 and 52 weeks
Fibrosis
Time frame: 52 weeks
Influence of liver disease on the quality of life
Time frame: 52 weeks
Treatment effect on health status
Time frame: 52 weeks
Cost-effectiveness based on empiric data obtained by this study.
Time frame: 52 weeks
Cost-effectiveness from a societal perspective
Time frame: 52 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Feb 2022.
- Derived from this study: PubMed 38233878Stoelinga AEC, Tushuizen ME, van den Hout WB, Girondo MDMR, de Vries ES, Levens AD, Moes DAR, Gevers TJG, van der Meer S, Brouwer HT, de Jonge HJM, de Boer YS, Beuers UHW, van der Meer AJ, van den Berg AP, Guichelaar MMJ, Drenth JPH, van Hoek B; Dutch Autoimmune Hepatitis Group. Tacrolimus versus mycophenolate for AutoImmune hepatitis patients with incompLete response On first-line therapy (TAILOR study): a study protocol for a phase III, open-label, multicentre, randomised controlled trial. Trials. 2024 Jan 17;25(1):61. doi: 10.1186/s13063-023-07832-w.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bart van Hoek contact
Bart van Hoek principal investigator
Leiden University Medical Center
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Mycophenolate Mofetil and Tacrolimus in people with Autoimmune Hepatitis, run by Leiden University Medical Center at 6 sites in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 3 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Anna Stoelinga (+31 6 30 29 11 71, a.e.c.stoelinga@lumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Complete biochemical remission (time frame: 52 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05221411, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Feb 2022.