Clinical trial NCT02293941: Liver Test Study of Using JKB-122 in Hepatitis C Virus (HCV)-Positive Patients Nonresponsive to Prior Interferon Based Therapies
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Chronic Hepatitis C
Keywords: liver inflammation
Lead sponsor: TaiwanJ Pharmaceuticals Co., Ltd
Sponsor class: INDUSTRY
First posted: 2014-11-19
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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:

1. Has history of allergy to JKB-122 or related compounds
2. Has human immunodeficiency virus (HIV) or is hepatitis B positive
3. Is with a current diagnosis of cirrhosis, both compensated and uncompensated Child-Pugh A, B or C
4. Has positive urine drug screen at Screening
5. 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)
6. Is being treated with any prescription narcotic drug (including transdermal delivery systems)
7. Has a known or suspected central nervous system disorder that may predispose to seizures or lower the seizure threshold
8. Has unstable and uncontrollable hypertension (\>180/110 mmHg)
9. 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)
10. Requires concomitant use of or treatment with opioids or other excluded drugs such as hepatotoxic medications
11. Has received other investigational agents within 30 days prior to the first screening visit (Day -28)
12. Has a disease that would require chronic use of prescription corticosteroids
13. Has either autoimmune or genetic liver disease
14. May be chronically or latently infected with microbial agents other than HCV
15. Has impaired renal function
16. Has BMI\> 30 or BMI \<18
17. If female, pregnant or lactating

Primary outcomes:
measure: ALT
timeFrame: baseline and 12 weeks
Secondary outcomes:
measure: Pharmacokinetic analysis (plasma concentration of JKB-122)
timeFrame: Day 1, 29, 57, 78
measure: Clinical laboratory tests (Includes hematology, coagulation, and serum chemistry.)
timeFrame: Screening, Day 1, 15, 29, 57, 85 and 30 days after EOS
Other outcomes:
Locations:
city: Changhua
country: Taiwan
facility: Changhua Christian Hospital
city: Chiayi City
country: Taiwan
facility: Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation
city: Chiayi City
country: Taiwan
facility: Chang Gung Memorial Hospital, Chiayi
city: Chiayi City
country: Taiwan
facility: Chia-Yi Christian Hospital
city: Kaohsiung
country: Taiwan
facility: Chang Gung Memorial Hospital, Kaohsiung
city: Keelung
country: Taiwan
facility: Chang Gung Memorial Hospital, Keelung
city: Tainan
country: Taiwan
facility: Chi Mei Medical Center - Liouying Branch
city: Tainan
country: Taiwan
facility: Chi Mei Hospital, YongKang Branch
city: Taipei
country: Taiwan
facility: Cathay General Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Taoyuan
country: Taiwan
facility: Chang Gung Memorial Hospital, Linkou
city: Yuanlin
country: Taiwan
facility: China Medical University Beigang Hospital
city: Yuanlin
country: Taiwan
facility: National Taiwan University Hospital, Yun-Lin Branch
Study officials:
affiliation: TaiwanJ Pharmaceuticals
name: Ying-Chu Shih, PhD
role: STUDY_DIRECTOR
References: