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

Sponsor

TaiwanJ Pharmaceuticals Co., Ltd (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT04371718

Collaborator

(none)

120

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

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

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

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

120 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A Phase II, Randomized, Double-Blind, Placebo Controlled, Trial of JKB-122 as an Adjunct Therapy to Prednisolone and Azathioprine in the Induction of Remission in Autoimmune Hepatitis (AIH)

Anticipated Study Start Date :

Nov 1, 2020

Anticipated Primary Completion Date :

Nov 1, 2023

Anticipated Study Completion Date :

Feb 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: JKB-122 Low dose JKB-122 5 mg daily for 104 weeks	Drug: JKB-122 JKB-122 is a TLR antagonist to immune modulate for autoimmune hepatitis
Experimental: JKB-122 Medium dose JKB-122, 15 mg daily for 104 weeks	Drug: JKB-122 JKB-122 is a TLR antagonist to immune modulate for autoimmune hepatitis
Experimental: JKB-122 High dose JKB-122 35 mg daily for 104 weeks	Drug: JKB-122 JKB-122 is a TLR antagonist to immune modulate for autoimmune hepatitis
Placebo Comparator: Placebo Matched placebo, daily for 104 weeks	Other: Placebo A capsule has same component but active drug

Outcome Measures

Primary Outcome Measures

Reduction of inflammation in Autoimmune Hepatitis [6, 12, and 24 months]
The % of patients in each treatment group who achieve biochemical remission

Secondary Outcome Measures

Steroid sparing effect [week 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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Male or female, 18 to 65 years old.
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.
Probable or definite diagnosis of autoimmune hepatitis according to the International Autoimmune Hepatitis Study Group criteria.
New diagnosis of AIH that requires treatment according to the current EASL guidelines.
Has elevated liver test results (ALT) at least 5x ULN at screening.
Is capable of understanding and signing the informed consent document.

Exclusion Criteria:

Overlap syndrome with Primary Sclerosing Cholangitis (PSC) or Primary Biliary Cholangitis (PBC)
Has cirrhosis on liver biopsy, or Child-Pugh score greater than 6 at screening.
Has human immunodeficiency virus (HIV) or is hepatitis B virus or HCV positive.
Has history of alcohol intake > 25 g/day within the past six months.
Severe anemia, leukopenia , or thrombocytopenia.
Known intolerances to prednisolone or azathioprine.
Current treatment with prednisone/prednisolone and/or immunosuppressive medication for an indication other than autoimmune hepatitis
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)
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.
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.