Liver Test Study of Using JKB-122 in Autoimmune Hepatitis (AIH) Patients Who Are Refractory or Intolerant to Current Therapies

Study Overview
=================
Brief Summary
-----------------
This is a Phase 2, pilot study in which JKB-122 is given once daily for 24 weeks in subjects with autoimmune hepatitis (AIH) who have liver enzymes that are 1.25 to 10 times the upper limit of normal (ULN) and who have had a failed response to, incomplete response to, intolerant to, ineligible to, or unwilling to take current immunosuppressant therapies. The dose of JKB-122 will be escalated monthly.

Detailed Description
-----------------
This is a Phase 2, pilot study in which JKB-122 is given once daily for 24 weeks to subjects with AIH who have liver enzymes that are 1.25 to 10 times the upper limit of normal (ULN) and who have had a failed response to, incomplete response to, intolerant to, ineligible to or unwilling to take current immunosuppressant therapies. Current immunosuppressant therapy is defined as prednisone or other steroids with or without azathioprine. Failed response is defined as being non-responsive to or worsening in symptoms (elevated Alanine Aminotransferase (ALT)/aspartate aminotransferase (AST) and/or total bilirubin) despite compliance with the standard of care (SOC) over a 6 months period. Incomplete response is defined as lack of a sustained normalization of elevated ALT/AST to current standard of care (SOC) for at least 6 months. Refractory to the current therapy includes patients who had a failed response to, or incomplete response to the current therapy. Subjects will be at least 18 years of age, either male or female and will have been on therapy for AIH and have not had a normalization of ALT with the current therapy.

Official Title
-----------------
A Phase 2, Pilot Study of JKB-122 to Assess Liver Tests (ALT) in Autoimmune Hepatitis (AIH) Patients Who Are Refractory or Intolerant to Current Therapies

Conditions
-----------------
Autoimmune Hepatitis

Intervention / Treatment
-----------------
* Drug: JKB-122


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Has definite or probable AIH diagnosis. Has had a liver biopsy or Fibroscan™ within 3 years and the severity of hepatic dysfunction is limited to the following: Metavir Stage 0 to stage 3 fibrosis (according to liver biopsy) or Fibroscan™ results ALT and AST values not exceeding 10x ULN Normal bilirubin and prothrombin time (PT/INR) Has elevated liver test results (ALT) at least 1.25 x ULN and not exceeding 10 x ULN at baseline. Has had a failed response, incomplete response, intolerant, ineligible or unwilling to take current immunosuppressive therapies. Current immunosuppressive therapy is defined as prednisone or other steroids with or without azathioprine. Exclusion Criteria: Has history of allergy to JKB-122 or related compounds Has human immunodeficiency virus (HIV) or is hepatitis B virus or hepatitis C virus (HCV) positive Has positive urine drug screen at Screening Has been diagnosed with other overlapping liver diseases such as primary biliary cirrhosis (PBC) or primary sclerosing cholangitis (PSC) Is currently consuming alcoholic drinks greater than 25g/day and within 3 months prior to the first screening visit. Is being treated with any prescription narcotic drug (including transdermal delivery systems) Concurrent medications within 30 days prior to screening: Opioids Thioridazine Silymarin and related medications Potentially hepatotoxic drugs Has a known or suspected central nervous system disorder that may predispose to seizures or lower the seizure threshold Has unstable and uncontrollable hypertension (>180/110 mmHg) or a blood pressure reading at baseline of 150/90 mmHg on 2 occasions separated by a 30 minute interval Is currently receiving dietary supplements other than a multivitamin to treat AIH Has received other investigational agents within 90 days prior to the first screening visit Has impaired renal function Has malignancy. If female, pregnant or lactating Has history of gastroesophageal varices, ascites, hepatic encephalopathy, hepatocellular carcinoma, and s/p liver transplantation

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Interventional Model Description: The patient takes 5mg up to 40mg depending on the monthly response.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: JKB-122<br>AIH-positive subjects (n=20) who are intolerant, refractory, ineligible or unwilling to take current therapies, and have liver enzymes that are 2 to 10 times the upper limit of normal | Drug: JKB-122<br>* Orally administered capsules of JKB-122 which will be taken once daily with dose escalation from 5mg up to 40mg depending on the monthly response.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in ALT in AIH subjects given daily doses of JKB-122 | To assess changes in ALT in AIH subjects given daily doses of JKB-122 | baseline and 24 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
AIH, JKB-122, autoimmune, hepatitis