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Effect of JKB-122 on Prednisolone and Azathioprine Induced Remission in Autoimmune Hepatitis (AIH)

Phase 2
Conditions
Autoimmune Hepatitis
Interventions
Other: Placebo
Registration Number
NCT04371718
Lead Sponsor
TaiwanJ Pharmaceuticals Co., Ltd
Brief Summary

This is a Phase 2 study. All patients will receive prednisolone and AZA as standard of care (SOC) during the study. At the end of the study, all data collected will be analyzed the efficacy and safety of JKB-122 on SOC reduction and inflammation improvement in Autoimmune Hepatitis

Detailed Description

JKB-122 has been demonstrated effective reducing aminotransferase in refractory AIH patients with SOC.This is a new Phase 2 study to find an optimal dose for relevant phase 3 study in newly diagnostic AIH patients. All patients will receive prednisolone and AZA as standard of care (SOC) during the study. Subjects will be randomized to receive 5 mg JKB-122, 15 mg JKB-122, 35 mg JKB-122 or placebo in 1:1:1:1 ratio, adjunct to SOC. This protocol with the primary endpoint being biochemical remission and evaluation of 3 different treatment doses. The histology will be explored as secondary to test long term benefit and to show similar trend with the biomarkers.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
120
Inclusion Criteria
  1. Male or female, 18 to 65 years old.
  2. If female of childbearing potential, must not be pregnant or breastfeeding and either postmenopausal (no menses for previous 12 months) or using an effective method of birth control.
  3. Probable or definite diagnosis of autoimmune hepatitis according to the International Autoimmune Hepatitis Study Group criteria.
  4. New diagnosis of AIH that requires treatment according to the current EASL guidelines.
  5. Has elevated liver test results (ALT) at least 5x ULN at screening.
  6. Is capable of understanding and signing the informed consent document.
Exclusion Criteria
  1. Overlap syndrome with Primary Sclerosing Cholangitis (PSC) or Primary Biliary Cholangitis (PBC)
  2. Has cirrhosis on liver biopsy, or Child-Pugh score greater than 6 at screening.
  3. Has human immunodeficiency virus (HIV) or is hepatitis B virus or HCV positive.
  4. Has history of alcohol intake > 25 g/day within the past six months.
  5. Severe anemia, leukopenia , or thrombocytopenia.
  6. Known intolerances to prednisolone or azathioprine.
  7. Current treatment with prednisone/prednisolone and/or immunosuppressive medication for an indication other than autoimmune hepatitis
  8. Has a known or suspected central nervous system disorder that may predispose to seizures or lower the seizure threshold
  9. Has unstable and uncontrollable hypertension (>180/110 mmHg)
  10. Has current malignancy or a history of malignancy (within the past 5 years), except basal or non-metastatic squamous cell carcinoma of the skin that has been treated successfully.
  11. Has any form of current substance abuse, psychiatric disorder or a condition that, in the opinion of the Investigator, may invalidate communication with the Investigator.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
JKB-122 Low doseJKB-122JKB-122 5 mg daily for 104 weeks
PlaceboPlaceboMatched placebo, daily for 104 weeks
JKB-122 High doseJKB-122JKB-122 35 mg daily for 104 weeks
JKB-122 Medium doseJKB-122JKB-122, 15 mg daily for 104 weeks
Primary Outcome Measures
NameTimeMethod
Reduction of inflammation in Autoimmune Hepatitis6, 12, and 24 months

The % of patients in each treatment group who achieve biochemical remission

Secondary Outcome Measures
NameTimeMethod
Steroid sparing effectweek 104

Steroid accumulation dose in overall or in those who achieve resolution of histology without worsening of the fibrosis

Changes in liver histology as measured by Hepatic Activity Index (HAI)Week 104

The reduction of inflammation in histology refers to improve Autoimmune Hepatitis disease status

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