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

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)

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

Study Overview

• Status: Not yet recruiting
• Conditions: Autoimmune Hepatitis
• Intervention / Treatment: Drug: JKB-122; Other: Placebo

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 Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Ying-Chu Shih, PhD; Phone Number: +88636587721; Email: info@TaiwanJ.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 61 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reduction of inflammation in Autoimmune Hepatitis	The % of patients in each treatment group who achieve biochemical remission	6, 12, and 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Steroid sparing effect	Steroid accumulation dose in overall or in those who achieve resolution of histology without worsening of the fibrosis	week 104
Changes in liver histology as measured by Hepatic Activity Index (HAI)	The reduction of inflammation in histology refers to improve Autoimmune Hepatitis disease status	Week 104

Collaborators and Investigators

• Sponsor: TaiwanJ Pharmaceuticals Co., Ltd

Study record dates

Study Major Dates

• Study Start (Anticipated): November 1, 2020
• Primary Completion (Anticipated): November 1, 2023
• Study Completion (Anticipated): February 1, 2024

Study Registration Dates

• First Submitted: April 29, 2020
• First Submitted That Met QC Criteria: April 29, 2020
• First Posted (Actual): May 1, 2020

Study Record Updates

• Last Update Posted (Actual): September 1, 2020
• Last Update Submitted That Met QC Criteria: August 28, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: Aminotransferase; ALT; Orphan Disease; Autoimmune Hepatitis; Steroid sparing
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Immune System Diseases; Autoimmune Diseases; Liver Diseases; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Hepatitis, Chronic; Hepatitis; Hepatitis A; Hepatitis, Autoimmune
• Other Study ID Numbers: JKB-122 AIH01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No