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

Sponsor

TaiwanJ Pharmaceuticals Co., Ltd (Industry)

Overall Status

Completed

CT.gov ID

NCT02556372

Collaborator

(none)

Enrollment

Locations

Arm

32.7

Actual Duration (Months)

1.3

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Autoimmune Hepatitis	Drug: JKB-122	Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

20 participants

Intervention Model:

Sequential Assignment

Intervention Model Description:

The patient takes 5mg up to 40mg depending on the monthly response.The patient takes 5mg up to 40mg depending on the monthly response.

Masking:

None (Open Label)

Masking Description:

This is an open label study

Primary Purpose:

Treatment

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

Actual Study Start Date :

Apr 30, 2016

Actual Primary Completion Date :

Jan 21, 2019

Actual Study Completion Date :

Jan 21, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: JKB-122 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 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.

Arm

Intervention/Treatment

Experimental: JKB-122

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

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.

Outcome Measures

Primary Outcome Measures

Changes in ALT in AIH subjects given daily doses of JKB-122 [baseline and 24 weeks]
To assess changes in ALT in AIH subjects given daily doses of JKB-122

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Ruane Clinical Research Group, Inc.	Los Angeles	California	United States	90036
2	University of California Davis Medical Center - Ticon 1	Sacramento	California	United States	95817
3	California Pacific Medical Center	San Francisco	California	United States
4	University of Florida Hepatology Research at CTRB	Gainesville	Florida	United States	32610-0272
5	Northwestern University	Chicago	Illinois	United States	60611
6	Indiana University School of Medicine	Indianapolis	Indiana	United States	46202
7	Tulane University	New Orleans	Louisiana	United States
8	Massachusetts General Hospital	Boston	Massachusetts	United States
9	Mount Sinai Hospital	New York	New York	United States	10029
10	Duke University Medical Center	Durham	North Carolina	United States	27710
11	Methodist Dallas Medical Center	Dallas	Texas	United States	75203
12	Advanced Liver Therapies, Baylor College of Medicine	Houston	Texas	United States	77030
13	The Texas Liver Institute	San Antonio	Texas	United States	78215
14	Taxes Liver Institute	San Antonio	Texas	United States
15	Swedish Medical Center - Organ Transplant and Liver Center	Seattle	Washington	United States	98104
16	University of Washington	Seattle	Washington	United States	98104