Clinical trial NCT02556372: Liver Test Study of Using JKB-122 in Autoimmune Hepatitis (AIH) Patients Who Are Refractory or Intolerant to Current Therapies
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Autoimmune Hepatitis
Keywords: AIH
JKB-122
autoimmune
hepatitis
Lead sponsor: TaiwanJ Pharmaceuticals Co., Ltd
Sponsor class: INDUSTRY
First posted: 2015-09-22
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Intervention model: SEQUENTIAL
Intervention model description: The patient takes 5mg up to 40mg depending on the monthly response.
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Changes in ALT in AIH subjects given daily doses of JKB-122
timeFrame: baseline and 24 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Ruane Clinical Research Group, Inc.
state: California
city: Sacramento
country: United States
facility: University of California Davis Medical Center - Ticon 1
state: California
city: San Francisco
country: United States
facility: California Pacific Medical Center
state: California
city: Gainesville
country: United States
facility: University of Florida Hepatology Research at CTRB
state: Florida
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University School of Medicine
state: Indiana
city: New Orleans
country: United States
facility: Tulane University
state: Louisiana
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: New York
country: United States
facility: Mount Sinai Hospital
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Dallas
country: United States
facility: Methodist Dallas Medical Center
state: Texas
city: Houston
country: United States
facility: Advanced Liver Therapies, Baylor College of Medicine
state: Texas
city: San Antonio
country: United States
facility: The Texas Liver Institute
state: Texas
city: San Antonio
country: United States
facility: Taxes Liver Institute
state: Texas
city: Seattle
country: United States
facility: Swedish Medical Center - Organ Transplant and Liver Center
state: Washington
city: Seattle
country: United States
facility: University of Washington
state: Washington
Study officials:
affiliation: TaiwanJ Pharmaceuticals
name: Ying-Chu Shih, PhD
role: STUDY_DIRECTOR
References:
citation: Chung YY, Rahim MN, Heneghan MA. Autoimmune hepatitis and pregnancy: considerations for the clinician. Expert Rev Clin Immunol. 2022 Apr;18(4):325-333. doi: 10.1080/1744666X.2022.2044307. Epub 2022 Mar 2.