Abatacept for Treatment of Recurrent or de Novo Autoimmune Hepatitis

Study Overview
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Brief Summary
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The purpose of this study is to evaluate whether Orencia® (Abatacept) improves outcomes in liver transplant patients with recurrent or de novo AIH (autoimmune hepatitis) that has not responded to previous therapy. AIH that does not respond to steroids or conventional immunotherapy often affects young patients and leads to irreversible liver damage. There is currently no effective therapy for this condition.

Detailed Description
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Participants in this study will receive the study drug once a week for 6 months. If the study doctor feels the study drug has been beneficial, participants may receive additional study drug doses for up to an additional 6 months. Participants will continue on follow-up for 1 year after stopping Abatacept. The risks related to participation in this study include potential side effects from the study drug include infusion-related reactions (reactions at the injection site), increase in respiratory adverse events, infections in patients with chronic obstructive pulmonary disease, risk of development of malignancies (cancer) or autoimmune disorders (which may make your current autoimmune disease worse or you can contract new autoimmune diseases). It is unknown if this is drug related. The study doctor will discuss any concerns about this with you prior to receiving treatment. There is the possibility that the participant may experience improvement in their medical condition from participation in this study. However, this benefit cannot be guaranteed. There may be no direct medical benefit to the participant due to their participation. The Investigator hopes that in the future the information learned from this study will benefit other people with this condition.

Official Title
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Abatacept for Treatment of Recurrent or de Novo Autoimmune Hepatitis

Conditions
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Autoimmune Hepatitis

Intervention / Treatment
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* Drug: Orencia® (Abatacept)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria for de novo AIH Age 18 or older Patients who have biopsy evidence of autoimmune liver disease following liver transplantation and a different pre-transplant etiology of liver disease will be eligible. Patients who have been treated with steroids or other immunosuppressive agents for at least a month and who have not responded either with respect to normalization of liver function tests or biopsy evidence of hepatitis will be eligible. Ability to provide signed and dated IRB approved written consent in accordance with regulatory and institutional guidelines prior to any protocol-related procedure. Women of child bearing potential agree to have pregnancy test at screening Males agree use of appropriate contraceptives during the active Orenia dosing period Inclusion Criteria for recurrent AIH Age 18 or older Patients who have biopsy evidence of autoimmune liver disease following liver transplantation and whose original etiology of liver disease was AIH will be eligible. Patients who have been treated with steroids or other immunosuppressive agents for at least a month and who have not responded either with respect to normalization of liver function tests or biopsy evidence of hepatitis will be eligible. Ability to provide signed and dated IRB approved written consent in accordance with regulatory and institutional guidelines prior to any protocol-related procedure. Women of child bearing potential agree to have pregnancy test at screening Males agree use of appropriate contraceptives during the active Orenia dosing period Exclusion Criteria: Active systemic infection Allergy to abatacept Known malignancy in the previous 2 years except for non-melanoma skin cancer Pregnancy or breast feeding Inability to commit to complete treatment protocol at Duke, as all procedures must be completed at Duke Prisoners or those who are compulsory detained Inability to read and understand English EBV seronegative (if not tested within 2 years prior to study enrollment, then testing will be done prior to study enrollment, results must be positive for study participation)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Orencia® (Abatacept)<br>Abatacept 125 mg, subcutaneous once a week for 6 months or up to one year if subject has a favorable response | Drug: Orencia® (Abatacept)<br>* Orencia® (Abatacept) will be administered once a week for 6 months subcutaneously (injection under the skin) with an option to continue to receive Abatacept weekly injections for an additional 6 months, for a total of 12 months if there is a positive response.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Adverse Events as reported | Any Adverse Event | within 56 days of last dose | 
| Number of Infections seen after administration | Any infection | within 56 days of last dose | 
| Number of malignancies reported | any malignancy | within 56 days of last dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| A change in aspartate aminotransferase (AST) | Any change | Baseline and at 6 weeks after start of administration | 
| A change in alanine aminotransferase (ALT) | Any change | Baseline and at 6 weeks after start of administration | 
| a change in alkaline phosphatase | Any change | Baseline and at 6 weeks after start of administration | 
| Change in bilirubin | Any change | Baseline and at 6 weeks after start of administration | 
| Change in liver biopsy evidence of AIH compared to pre-treatment | evidence of worsening AIH on biopsy | through study completion, an average of 1 year |