JKB-121 for the Treatment of Nonalcoholic Steatohepatitis

NCT ID: NCT02442687

Last Updated: 2019-01-07

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

65 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-08-01

Study Completion Date

2017-09-24

Brief Summary

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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

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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.

Conditions

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Nonalcoholic Steatohepatitis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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A

JKB 121, 5 mg twice daily

Group Type ACTIVE_COMPARATOR

JKB-121: 5 mg twice daily

Intervention Type DRUG

B

JKB 121, 10 mg twice daily

Group Type ACTIVE_COMPARATOR

JKB-121: 10 mg twice daily

Intervention Type DRUG

C

Identical appearing placebo

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Interventions

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JKB-121: 5 mg twice daily

Intervention Type DRUG

JKB-121: 10 mg twice daily

Intervention Type DRUG

Placebo

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Manal Abdelmalek

OTHER

Sponsor Role lead

Responsible Party

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Manal Abdelmalek

Associate Professor

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Manal F Abdelmalek, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

Duke University

Locations

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Digestive Disease Specialists of the Southeast

Dothan, Alabama, United States

Site Status

Northwestern University Feinberg School of Medicine

Chicago, Illinois, United States

Site Status

Digestive Associates

Las Vegas, Nevada, United States

Site Status

Duke University

Durham, North Carolina, United States

Site Status

Digestive Disease Specialists

Cincinnati, Ohio, United States

Site Status

Brook Army Medical Center

Houston, Texas, United States

Site Status

University of Virginia Health Systems

Charlottesville, Virginia, United States

Site Status

Medical College of Virginia

Richmond, Virginia, United States

Site Status

Countries

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United States

References

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Nedrud MA, Chaudhry M, Middleton MS, Moylan CA, Lerebours R, Luo S, Farjat A, Guy C, Loomba R, Abdelmalek MF, Sirlin CB, Bashir MR. MRI Quantification of Placebo Effect in Nonalcoholic Steatohepatitis Clinical Trials. Radiology. 2023 Mar;306(3):e220743. doi: 10.1148/radiol.220743. Epub 2022 Nov 1.

Reference Type DERIVED
PMID: 36318027 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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Pro00062677

Identifier Type: -

Identifier Source: org_study_id

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