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JKB-121 for the Treatment of Nonalcoholic Steatohepatitis

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Manal Abdelmalek, Duke University Medical Center
ClinicalTrials.gov Identifier:
NCT02442687
First received: April 7, 2015
Last updated: January 26, 2017
Last verified: January 2017

April 7, 2015
January 26, 2017
August 1, 2015
July 31, 2017   (Final data collection date for primary outcome measure)
  • Rate of patients who experience one or more adverse events (AE) [ Time Frame: Week 24 ]
  • Rate of patients who experience serious adverse events (SAE) [ Time Frame: Week 24 ]
  • Rate of patients who experience AEs leading to discontinuation of study medication [ Time Frame: Week 24 ]
  • Rate of patients who experience adverse events in each grade of the Common Terminology Criteria for Adverse Events (CTCAE) v3.0 [ Time Frame: Week 24 ]
  • Mean change from baseline in the percentage fat content of the liver measured by magnetic resonance imaging and spectroscopy (MRI/MRS) at week 24 [ Time Frame: Baseline, week 24 ]
  • Mean change from baseline in serum ALT at week 24 [ Time Frame: Baseline, week 24 ]
  • Time to remission (TTR), in weeks [ Time Frame: 24 weeks ]
    TTR is defined as time, in weeks, from randomization to liver function remission as defined as two consecutive ALT values within normal range (< 40 IU/mL) during study period.
Same as current
Complete list of historical versions of study NCT02442687 on ClinicalTrials.gov Archive Site
  • Maximum observed concentrations (Cmax) of JKB-121 serum concentration [ Time Frame: day 1, week 8, 16, and 24 ]
    Intensive PK will be performed in a subset of patients on day 1 with pharmacologic trough levels on week 8, 16, and 24.
  • Minimum observed concentration (Cmin) of JKB-121 serum concentration [ Time Frame: day 1, week 8, 16, and 24 ]
    Intensive PK will be performed in a subset of patients on day 1 with pharmacologic trough levels on week 8, 16, and 24.
  • Area under the concentration time curve (AUC) of JKB-121 serum concentration [ Time Frame: day 1, week 8, 16, and 24 ]
    Intensive PK will be performed in a subset of patients on day 1 with pharmacologic trough levels on week 8, 16, and 24.
  • JKB-121 Half-life (t½) [ Time Frame: day 1, week 8, 16, and 24 ]
    Intensive PK will be performed in a subset of patients on day 1 with pharmacologic trough levels on week 8, 16, and 24.
  • Change in body mass index (BMI) [ Time Frame: monthly, up to 24 weeks ]
  • Change in waist circumference [ Time Frame: monthly, up to 24 weeks ]
  • Change in HBA1C [ Time Frame: monthly, up to 24 weeks ]
  • Change in homeostatic model assessment of insulin resistance (HOMA-IR) [ Time Frame: monthly, up to 24 weeks ]
  • Change in total cholesterol [ Time Frame: monthly, up to 24 weeks ]
  • Change in triglycerides [ Time Frame: monthly, up to 24 weeks ]
  • Change in low density lipoprotein (LDL) [ Time Frame: monthly, up to 24 weeks ]
  • Change in high density lipoprotein (HDL) [ Time Frame: monthly, up to 24 weeks ]
  • Change in serum aspartate aminotransferase (AST) [ Time Frame: weeks 4, 8, 12, 16, 20, and 24 ]
  • Change in serum alanine aminotransferase (ALT) [ Time Frame: weeks 4, 8, 12, 16, 20, and 24 ]
  • Change in serum gamma-glutamyl transpeptidase (GGT) [ Time Frame: weeks 4, 8, 12, 16, 20, and 24 ]
  • Proportion of subjects whose ALT level at week 24 is within normal range defined as < 20 U/L for women and < 30 U/L for men [ Time Frame: 24 weeks ]
Same as current
Not Provided
Not Provided
 
JKB-121 for the Treatment of Nonalcoholic Steatohepatitis
A Randomized, Double-Blind, Placebo Controlled, Parallel-Group, Phase II Trial of JKB-121 for the Treatment of Nonalcoholic Steatohepatitis (NASH)
To evaluate the safety and potential efficacy of two dose levels of JKB-121 (5 mg twice daily and 10 mg twice daily) in reducing liver fat and/or liver biochemistry compared to placebo in patients with biopsy-proven nonalcoholic steatohepatitis
JKB-121 is a long-acting small molecule that is efficacious as a weak antagonist at the TLR-4 receptor. It is a non-selective opioid antagonist which has been shown to prevent the lipopolysaccharide (LPS) induced inflammatory liver injury in a methionine/choline deficient diet fed rat model of nonalcoholic fatty liver disease. In vitro, JKB-121 neutralized or reduced the LPS-induced release of inflammatory cytokines, deactivated hepatic stellate cells, inhibited hepatic stellate cell proliferation, and collagen expression. Inhibition of the TLR4 signaling pathway may provide an effective therapy in the prevention of inflammatory hepatic injury and hepatic fibrosis in patients with nonalcoholic steatohepatitis. This study will evaluate the safety and potential efficacy of two dose levels of JKB-121 (5 mg twice daily and 10 mg twice daily) in reducing liver fat and/or liver biochemistry compared to placebo in patients with biopsy-proven nonalcoholic steatohepatitis.
Interventional
Phase 2
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Participant, Care Provider, Investigator, Outcomes Assessor
Primary Purpose: Treatment
Nonalcoholic Steatohepatitis
  • Drug: JKB-121: 5 mg twice daily
  • Drug: JKB-121: 10 mg twice daily
  • Drug: Placebo
  • Active Comparator: A
    JKB 121, 5 mg twice daily
    Intervention: Drug: JKB-121: 5 mg twice daily
  • Active Comparator: B
    JKB 121, 10 mg twice daily
    Intervention: Drug: JKB-121: 10 mg twice daily
  • Placebo Comparator: C
    Identical appearing placebo
    Intervention: Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
66
December 31, 2017
July 31, 2017   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  1. Age ≥ 18 years
  2. Provision of written informed consent
  3. Biopsy-proven NASH within 12 months or at screening
  4. ALT > 40 U/L for women and > 60 U/L for men at screening and at least once in the previous 12 months.
  5. HBA1C of ≤ 9.0

Exclusion Criteria:

  1. Any chronic liver disease other than NASH
  2. Cirrhosis, as assessed clinically or histologically
  3. Presence of vascular liver disease
  4. BMI ≤ 25 kg/m2
  5. Excessive alcohol use (> 20 g/day) within the past 2 years
  6. AST or ALT > 250 U/L.
  7. Type 1 diabetes mellitus
  8. Bariatric surgery in the past 5 years.
  9. Weight gain of > 5% in past 6 months or > 10% change in past 12 months.
  10. Contraindication to MRI
  11. Inadequate venous access
  12. HIV antibody positive, hepatitis B surface antigen positive (HBsAg), or Hepatitis C virus (HCV) RNA positive.
  13. Receiving an elemental diet or parenteral nutrition
  14. Chronic pancreatitis or pancreatic insufficiency
  15. Any history of complications of cirrhosis
  16. Concurrent conditions:

    • Inflammatory bowel disease
    • Significant cardiac disease
    • chronic infection or immune mediated disease
    • Any malignant disease
    • Prior solid organ transplant
    • Any other concurrent condition which, in the opinion of the investigator, could impact adversely on the subject participating or the interpretation of the study data.
  17. Concurrent medications which may treat NASH
  18. HbA1C > 9.0%
  19. Pregnancy or breastfeeding.
Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT02442687
Pro00062677
Yes
Not Provided
Not Provided
Not Provided
Manal Abdelmalek, Duke University Medical Center
Manal Abdelmalek
Not Provided
Principal Investigator: Manal F Abdelmalek, MD, MPH Duke University
Duke University
January 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP