Liver Test Study of Using JKB-122 in Hepatitis C Virus (HCV)-Positive Patients Nonresponsive to Prior Interferon Based Therapies

Study Overview
=================
Brief Summary
-----------------
The primary objective of this study is to assess changes in alanine aminotransferase (ALT) in hepatitis C virus (HCV)-infected subjects given daily doses of JKB-122 for 3 months who have been nonresponsive to, intolerable to, or relapsed from prior interferon-based therapies (pegylated or standard) either alone or in combination with ribavirin or other anti-HCV therapies including direct-acting anti-viral agents.

Official Title
-----------------
A Phase 2, Randomized, Multiple-dose, Double-blind, Placebo-controlled Study of JKB-122 to Assess Liver Tests in HCV Subjects Who Have Been Nonresponsive to Prior Interferon Based Therapies Either Alone or in Combination With Ribavirin

Conditions
-----------------
Chronic Hepatitis C

Intervention / Treatment
-----------------
* Drug: JKB-122 5mg
* Drug: JKB-122 15mg
* Drug: JKB-122 35mg
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Is HCV positive (documented by HCV RNA testing at Screening). Chronic hepatitis C is defined as a) Positive for anti-HCV antibody, HCV RNA, or an HCV genotype at least 6 months before screening, and positive for HCV RNA and anti-HCV antibody at the time of screening; or b) Positive for anti-HCV antibody and HCV RNA at the time of screening with a liver biopsy consistent with chronic HCV infection (or a liver biopsy performed before enrollment with evidence of CHC disease, such as the presence of fibrosis), according to Guidance for Industry. Chronic Hepatitis C Virus Infection: Developing Direct-Acting Antiviral Agents for Treatment. Has previous results from HCV genotype testing. If previous results are not available, such testing should be performed at Screening. 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 5 x ULN (Baseline value for each parameter will be calculated as the average of 3 values obtained 7 days apart Normal total bilirubin, and prothrombin time/INR values Has elevated liver test results (ALT) at least 1.5 x ULN and not exceeding 5 x ULN (Baseline value for each parameter will be calculated as the average of 3 values obtained 7 days apart Is refractory or null responder, intolerable, relapser, or partial responder. Null responder is defined as less than a 2 log10 IU/mL reduction in HCV RNA after 12 weeks of treatment with standard or Peg Interferon/ribavirin or other anti-HCV therapies; Relapser is defined as HCV RNA undetectable (or negative, per site's definition) at the end stage of treatment with a standard or pegylated interferon-based regimen or other anti-HCV therapies, but HCV RNA detectable during post-treatment follow-up; The intolerable is defined as HCV patients who cannot tolerate the side effects of previous interferon-based therapies or other anti-HCV therapies, or who were not suitable for interferon-based therapies or other anti-HCV therapies; Partial responder is defined as achieved more than 2 log10 IU/mL reduction in HCV RNA by Week 12 (± 1 week) during a prior pegIFN/RBV treatment course or other anti-HCV therapies but failed to achieve HCV RNA undetectable at the end stage of treatment. Exclusion Criteria: Has history of allergy to JKB-122 or related compounds Has human immunodeficiency virus (HIV) or is hepatitis B positive Is with a current diagnosis of cirrhosis, both compensated and uncompensated Child-Pugh A, B or C Has positive urine drug screen at Screening Is currently consuming greater than 30 g of alcohol per day (eg, 2 highballs with 1 shot each, or 2 beers) or has consumed greater than 2 glasses of alcohol per day within 3 months prior to the first screening visit (Day -28) Is being treated with any prescription narcotic drug (including transdermal delivery systems) 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 received other therapies for HCV infection (interferon, pegylated interferon, ribavirin, or others) in the last 4 weeks prior to the first screening visit (Day -28) Requires concomitant use of or treatment with opioids or other excluded drugs such as hepatotoxic medications Has received other investigational agents within 30 days prior to the first screening visit (Day -28) Has a disease that would require chronic use of prescription corticosteroids Has either autoimmune or genetic liver disease May be chronically or latently infected with microbial agents other than HCV Has impaired renal function Has BMI> 30 or BMI <18 If female, pregnant or lactating

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: JKB-122 5mg<br>5mg, oral, once daily | Drug: JKB-122 5mg<br>* Participants were randomized to receive JKB-122 5mg for 12 weeks<br>|
| Experimental: JKB-122 15 mg<br>15mg, oral, once daily | Drug: JKB-122 15mg<br>* Participants were randomized to receive JKB-122 15mg for 12 weeks<br>|
| Experimental: JKB-122 35 mg<br>35mg, oral, once daily | Drug: JKB-122 35mg<br>* Participants were randomized to receive JKB-122 35mg for 12 weeks<br>|
| Placebo Comparator: placebo<br>comparable capsule, oral, once daily | Drug: Placebo<br>* Participants were randomized to receive comparable placebo for 12 weeks<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ALT | To assess changes in ALT in HCV-infected subjects given daily doses of JKB-122 | baseline and 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic analysis (plasma concentration of JKB-122) | plasma concentration of JKB-122 will be measured for exploration of exposure/response relationships in all subjects of each dose group at Stage 1. | Day 1, 29, 57, 78 | 
| Clinical laboratory tests (Includes hematology, coagulation, and serum chemistry.) | Includes hematology, coagulation, and serum chemistry. | Screening, Day 1, 15, 29, 57, 85 and 30 days after EOS | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
liver inflammation