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Completed

NCT Number: NCT02442687

JKB-121 for the Treatment of Nonalcoholic Steatohepatitis

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

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Key information

Conditions

Nonalcoholic Steatohepatitis Digestive System Diseases Fatty Liver Liver Diseases Non-alcoholic Fatty Liver Disease

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Digestive Disease Specialists of the Southeast, Dothan, Alabama, United States

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

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

Exclusion criteria

  • Any chronic liver disease other than NASH
  • Cirrhosis, as assessed clinically or histologically
  • Presence of vascular liver disease
  • BMI ≤ 25 kg/m2
  • Excessive alcohol use (> 20 g/day) within the past 2 years
  • AST or ALT > 250 U/L.
  • Type 1 diabetes mellitus
  • Bariatric surgery in the past 5 years.
  • Weight gain of > 5% in past 6 months or > 10% change in past 12 months.
  • Contraindication to MRI
  • Inadequate venous access
  • HIV antibody positive, hepatitis B surface antigen positive (HBsAg), or Hepatitis C virus (HCV) RNA positive.
  • Receiving an elemental diet or parenteral nutrition
  • Chronic pancreatitis or pancreatic insufficiency
  • Any history of complications of cirrhosis
  • 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.
  • Concurrent medications which may treat NASH
  • HbA1C > 9.0%
  • Pregnancy or breastfeeding.

Treatment and study plan

JKB-121: 5 mg twice daily

Drug

JKB-121: 10 mg twice daily

Drug

Placebo

Drug

Primary outcomes

  1. Analysis of MRI-PDFF Change From Baseline to Week 24 (Per Protocol Population)

    Time frame: Baseline to week 24

  2. Analysis of MRI-PDFF Change From Baseline to Week 12 (Per Protocol Population)

    Time frame: Baseline to Week 12

Secondary outcomes

  1. Analysis of ALT Change From Baseline to Week 24 (Per Protocol Population)

    Time frame: Baseline to week 24

  2. Analysis of ALT Change From Baseline to Week 12 (Per Protocol Population)

    Time frame: Baseline to week 12

  3. Time to Remission (in Weeks)

    Time frame: 24 weeks

    Time to remission is the time in weeks from randomization to liver function remission, defined as two consecutive ALT values within normal range (<40 U/L) during the treatment period.

  4. Change in BMI (Body Mass Index)

    Time frame: Baseline, week 24

  5. Change in Hemoglobin A1C

    Time frame: Baseline, week 24

  6. Change in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)

    Time frame: Baseline, week 24

    HOMA-IR was calculated according to the formula: fasting insulin (microU/L) x fasting glucose (nmol/L)/22.5. Optimal Range: 1.0 (0.5-1.4). Lower values represent a better outcome.

  7. Percent Change in Cholesterol

    Time frame: Baseline, week 24

  8. Percent Change in Triglycerides

    Time frame: Baseline, week 24

  9. Percent Change in Low Density Lipoprotein (LDL) Cholesterol

    Time frame: Baseline, week 24

  10. Percent Change in High Density Lipoprotein (HDL)

    Time frame: Baseline, week 24

  11. Mean Serum Aspartate Aminotransferase (AST)

    Time frame: weeks 4, 8, 12, 16, 20, and 24

  12. Mean Serum Alanine Aminotransferase (ALT)

    Time frame: weeks 4, 8, 12, 16, 20, and 24

  13. Mean Serum Gamma-glutamyl Transpeptidase (GGT)

    Time frame: weeks 4, 8, 12, 16, 20, and 24

  14. Number of Subjects With ALT in Normal Range at Week 24

    Time frame: Week 24

    Normal range is <40 U/L

  15. Maximum Observed Concentrations (Cmax)

    Time frame: pre-dose and at 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 10, 12, and 24 hours

  16. Minimum Observed Concentration (Cmin)

    Time frame: pre-dose and at 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 10, 12, and 24 hours

  17. Area Under Concentration-time (AUC)

    Time frame: pre-dose and at 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 10, 12, and 24 hours

  18. Half-life

    Time frame: pre-dose and at 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 10, 12, and 24 hours

Sponsors and collaborators

Lead sponsor

Manal Abdelmalek

Other

Registry information

Official study title

A Randomized, Double-Blind, Placebo Controlled, Parallel-Group, Phase II Trial of JKB-121 for the Treatment of Nonalcoholic Steatohepatitis (NASH)

Important dates

Study start
2015
Primary completion
2017
Study completion
2017
First posted
May 13, 2015
Registry last updated
Jan 7, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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