Back to resultsJKB-121 for the Treatment of Nonalcoholic Steatohepatitis
Primary Purpose
Nonalcoholic Steatohepatitis
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
JKB-121: 5 mg twice daily
JKB-121: 10 mg twice daily
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Nonalcoholic Steatohepatitis
Eligibility Criteria
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.
Sites / Locations
- Digestive Disease Specialists of the Southeast
- Northwestern University Feinberg School of Medicine
- Digestive Associates
- Duke University
- Digestive Disease Specialists
- Brook Army Medical Center
- University of Virginia Health Systems
- Medical College of Virginia
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Active Comparator
Active Comparator
Placebo Comparator
Arm Label
A
B
C
Arm Description
JKB 121, 5 mg twice daily
JKB 121, 10 mg twice daily
Identical appearing placebo
Outcomes
Primary Outcome Measures
Analysis of MRI-PDFF Change From Baseline to Week 24 (Per Protocol Population)
Analysis of MRI-PDFF Change From Baseline to Week 12 (Per Protocol Population)
Secondary Outcome Measures
Analysis of ALT Change From Baseline to Week 24 (Per Protocol Population)
Analysis of ALT Change From Baseline to Week 12 (Per Protocol Population)
Time to Remission (in 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.
Change in BMI (Body Mass Index)
Change in Hemoglobin A1C
Change in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)
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.
Percent Change in Cholesterol
Percent Change in Triglycerides
Percent Change in Low Density Lipoprotein (LDL) Cholesterol
Percent Change in High Density Lipoprotein (HDL)
Mean Serum Aspartate Aminotransferase (AST)
Mean Serum Alanine Aminotransferase (ALT)
Mean Serum Gamma-glutamyl Transpeptidase (GGT)
Number of Subjects With ALT in Normal Range at Week 24
Normal range is <40 U/L
Maximum Observed Concentrations (Cmax)
Minimum Observed Concentration (Cmin)
Area Under Concentration-time (AUC)
Half-life
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02442687
Brief Title
JKB-121 for the Treatment of Nonalcoholic Steatohepatitis
Official Title
A Randomized, Double-Blind, Placebo Controlled, Parallel-Group, Phase II Trial of JKB-121 for the Treatment of Nonalcoholic Steatohepatitis (NASH)
Study Type
Interventional
2. Study Status
Record Verification Date
December 2018
Overall Recruitment Status
Completed
Study Start Date
August 1, 2015 (Actual)
Primary Completion Date
September 24, 2017 (Actual)
Study Completion Date
September 24, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Manal Abdelmalek
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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
Detailed Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Nonalcoholic Steatohepatitis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
65 (Actual)
8. Arms, Groups, and Interventions
Arm Title
A
Arm Type
Active Comparator
Arm Description
JKB 121, 5 mg twice daily
Arm Title
B
Arm Type
Active Comparator
Arm Description
JKB 121, 10 mg twice daily
Arm Title
C
Arm Type
Placebo Comparator
Arm Description
Identical appearing placebo
Intervention Type
Drug
Intervention Name(s)
JKB-121: 5 mg twice daily
Intervention Type
Drug
Intervention Name(s)
JKB-121: 10 mg twice daily
Intervention Type
Drug
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
Analysis of MRI-PDFF Change From Baseline to Week 24 (Per Protocol Population)
Time Frame
Baseline to week 24
Title
Analysis of MRI-PDFF Change From Baseline to Week 12 (Per Protocol Population)
Time Frame
Baseline to Week 12
Secondary Outcome Measure Information:
Title
Analysis of ALT Change From Baseline to Week 24 (Per Protocol Population)
Time Frame
Baseline to week 24
Title
Analysis of ALT Change From Baseline to Week 12 (Per Protocol Population)
Time Frame
Baseline to week 12
Title
Time to Remission (in Weeks)
Description
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.
Time Frame
24 weeks
Title
Change in BMI (Body Mass Index)
Time Frame
Baseline, week 24
Title
Change in Hemoglobin A1C
Time Frame
Baseline, week 24
Title
Change in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)
Description
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.
Time Frame
Baseline, week 24
Title
Percent Change in Cholesterol
Time Frame
Baseline, week 24
Title
Percent Change in Triglycerides
Time Frame
Baseline, week 24
Title
Percent Change in Low Density Lipoprotein (LDL) Cholesterol
Time Frame
Baseline, week 24
Title
Percent Change in High Density Lipoprotein (HDL)
Time Frame
Baseline, week 24
Title
Mean Serum Aspartate Aminotransferase (AST)
Time Frame
weeks 4, 8, 12, 16, 20, and 24
Title
Mean Serum Alanine Aminotransferase (ALT)
Time Frame
weeks 4, 8, 12, 16, 20, and 24
Title
Mean Serum Gamma-glutamyl Transpeptidase (GGT)
Time Frame
weeks 4, 8, 12, 16, 20, and 24
Title
Number of Subjects With ALT in Normal Range at Week 24
Description
Normal range is <40 U/L
Time Frame
Week 24
Title
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
Title
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
Title
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
Title
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Manal F Abdelmalek, MD, MPH
Organizational Affiliation
Duke University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Digestive Disease Specialists of the Southeast
City
Dothan
State/Province
Alabama
ZIP/Postal Code
36305
Country
United States
Facility Name
Northwestern University Feinberg School of Medicine
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Digestive Associates
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89102
Country
United States
Facility Name
Duke University
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Digestive Disease Specialists
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45219
Country
United States
Facility Name
Brook Army Medical Center
City
Houston
State/Province
Texas
ZIP/Postal Code
78234
Country
United States
Facility Name
University of Virginia Health Systems
City
Charlottesville
State/Province
Virginia
ZIP/Postal Code
22903
Country
United States
Facility Name
Medical College of Virginia
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Undecided
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JKB-121 for the Treatment of Nonalcoholic Steatohepatitis
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