Abatacept for Treatment of Recurrent or de Novo Autoimmune Hepatitis

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.

Study Overview

• Status: Terminated
• Conditions: Autoimmune Hepatitis
• Intervention / Treatment: Drug: Orencia® (Abatacept)

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27720
      • Duke University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Orencia® (Abatacept); Abatacept 125 mg, subcutaneous once a week for 6 months or up to one year if subject has a favorable response	Drug: Orencia® (Abatacept); 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Stuart Knechtle, M.D.

Study record dates

Study Major Dates

• Study Start (Actual): March 9, 2020
• Primary Completion (Actual): July 23, 2020
• Study Completion (Actual): July 23, 2020

Study Registration Dates

• First Submitted: December 12, 2019
• First Submitted That Met QC Criteria: December 17, 2019
• First Posted (Actual): December 18, 2019

Study Record Updates

• Last Update Posted (Actual): November 29, 2021
• Last Update Submitted That Met QC Criteria: November 17, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Immune System Diseases; Autoimmune Diseases; Liver Diseases; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Hepatitis, Chronic; Hepatitis; Hepatitis A; Hepatitis, Autoimmune; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Immune Checkpoint Inhibitors; Abatacept
• Other Study ID Numbers: Pro00102357

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: There are no plans to share IPD at this time

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No