Nonalcoholic SteatohepatitisPhase 2NCT02442687
JKB-121 for the Treatment of Nonalcoholic Steatohepatitis
A Phase 2 study testing JKB-121: 5 mg twice daily and JKB-121: 10 mg twice daily in people with Nonalcoholic Steatohepatitis, run by Manal Abdelmalek at 8 sites in United States.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Nonalcoholic Steatohepatitis
- What is being tested?
- JKB-121: 5 mg twice daily and JKB-121: 10 mg twice daily
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 65 participants
- Where
- 8 sitesUnited States
- Study dates
- 1 Aug 2015to 24 Sep 2017
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Show all 25Show fewer
- 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.
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
United States8 sites
University of Virginia Health Systems
Charlottesville, Virginia, 22903
Northwestern University Feinberg School of Medicine
Chicago, Illinois, 60611
Digestive Disease Specialists
Cincinnati, Ohio, 45219
Digestive Disease Specialists of the Southeast
Dothan, Alabama, 36305
Duke University
Durham, North Carolina, 27710
Brook Army Medical Center
Houston, Texas, 78234
Digestive Associates
Las Vegas, Nevada, 89102
Medical College of Virginia
Richmond, Virginia, 23298
About this study
Official title: 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
Read the 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.
- Conditions
- Nonalcoholic Steatohepatitis
- Being tested
- JKB-121: 5 mg twice daily, JKB-121: 10 mg twice daily, Placebo
- Medical subject headings
- Non-alcoholic Fatty Liver Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
JKB-121: 5 mg twice dailyDrug
JKB-121: 10 mg twice dailyDrug
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| A | Active comparator | JKB 121, 5 mg twice daily Receives: Drug: JKB-121: 5 mg twice daily |
| B | Active comparator | JKB 121, 10 mg twice daily Receives: Drug: JKB-121: 10 mg twice daily |
| C | Placebo comparator | Identical appearing placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Analysis of MRI-PDFF Change From Baseline to Week 24 (Per Protocol Population)
Measured: Baseline to week 24
Analysis of MRI-PDFF Change From Baseline to Week 12 (Per Protocol Population)
Measured: Baseline to Week 12
Secondary outcomes (18)
Analysis of ALT Change From Baseline to Week 24 (Per Protocol Population)
Measured: Baseline to week 24
Analysis of ALT Change From Baseline to Week 12 (Per Protocol Population)
Measured: Baseline to week 12
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.
Measured: 24 weeks
Change in BMI (Body Mass Index)
Measured: Baseline, week 24
Change in Hemoglobin A1C
Measured: Baseline, week 24
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.
Measured: Baseline, week 24
Percent Change in Cholesterol
Measured: Baseline, week 24
Percent Change in Triglycerides
Measured: Baseline, week 24
Percent Change in Low Density Lipoprotein (LDL) Cholesterol
Measured: Baseline, week 24
Percent Change in High Density Lipoprotein (HDL)
Measured: Baseline, week 24
Mean Serum Aspartate Aminotransferase (AST)
Measured: weeks 4, 8, 12, 16, 20, and 24
Mean Serum Alanine Aminotransferase (ALT)
Measured: weeks 4, 8, 12, 16, 20, and 24
Mean Serum Gamma-glutamyl Transpeptidase (GGT)
Measured: weeks 4, 8, 12, 16, 20, and 24
Number of Subjects With ALT in Normal Range at Week 24
Normal range is <40 U/L
Measured: Week 24
Maximum Observed Concentrations (Cmax)
Measured: 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
Minimum Observed Concentration (Cmin)
Measured: 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
Area Under Concentration-time (AUC)
Measured: 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
Half-life
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 May 2015 (estimated)
- Study start1 Aug 2015
- Primary completion24 Sep 2017
- Study completion24 Sep 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Nonalcoholic SteatohepatitisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 65 participants (actual)
Sponsor and investigators
- Lead sponsor
- Manal Abdelmalek
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Manal Abdelmalek, Duke University
- Investigators
- Manal F Abdelmalek, MD, MPH, Principal investigator, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02442687
- Sponsor's protocol ID
- Pro00062677
- Status last verified
- Dec 2018
- First submitted
- 7 Apr 2015
- Last updated
- 7 Jan 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 36318027
Study at a glance
From the registry record, last updated by the sponsor on 7 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-Blind, Placebo Controlled, Parallel-Group, Phase II Trial of JKB-121 for the Treatment of Nonalcoholic Steatohepatitis (NASH)
- ClinicalTrials.gov ID
- NCT02442687
- Acronym / sponsor ID
- Pro00062677
- Conditions
- Nonalcoholic Steatohepatitis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 65 participants (actual)
- Lead sponsor
- Manal AbdelmalekUniversity, hospital or other
- Study start
- 1 Aug 2015 (actual)
- Primary completion
- 24 Sep 2017 (actual)
- Study completion
- 24 Sep 2017 (actual)
- First posted
- 13 May 2015 (estimated)
- Results
- Posted 7 Jan 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| A | Active comparator | Drug: JKB-121: 5 mg twice dailyJKB 121, 5 mg twice daily |
| B | Active comparator | Drug: JKB-121: 10 mg twice dailyJKB 121, 10 mg twice daily |
| C | Placebo comparator | Drug: PlaceboIdentical appearing placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (25 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| JKB-121: 5 mg twice daily | Drug | A |
| JKB-121: 10 mg twice daily | Drug | B |
| Placebo | Drug | C |
Primary outcome
Analysis of MRI-PDFF Change From Baseline to Week 24 (Per Protocol Population)
Time frame: Baseline to week 24
Analysis of MRI-PDFF Change From Baseline to Week 12 (Per Protocol Population)
Time frame: Baseline to Week 12
18 secondary outcomes
Analysis of ALT Change From Baseline to Week 24 (Per Protocol Population)
Time frame: Baseline to week 24
Analysis of ALT Change From Baseline to Week 12 (Per Protocol Population)
Time frame: Baseline to week 12
Time to Remission (in Weeks)
Time frame: 24 weeks
Change in BMI (Body Mass Index)
Time frame: Baseline, week 24
Change in Hemoglobin A1C
Time frame: Baseline, week 24
Change in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)
Time frame: Baseline, week 24
Percent Change in Cholesterol
Time frame: Baseline, week 24
Percent Change in Triglycerides
Time frame: Baseline, week 24
Percent Change in Low Density Lipoprotein (LDL) Cholesterol
Time frame: Baseline, week 24
Percent Change in High Density Lipoprotein (HDL)
Time frame: Baseline, week 24
Mean Serum Aspartate Aminotransferase (AST)
Time frame: weeks 4, 8, 12, 16, 20, and 24
Mean Serum Alanine Aminotransferase (ALT)
Time frame: weeks 4, 8, 12, 16, 20, and 24
Mean Serum Gamma-glutamyl Transpeptidase (GGT)
Time frame: weeks 4, 8, 12, 16, 20, and 24
Number of Subjects With ALT in Normal Range at Week 24
Time frame: Week 24
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
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
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
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jan 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36318027Nedrud 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Manal F Abdelmalek, MD, MPH principal investigator
Duke University
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing JKB-121: 5 mg twice daily and JKB-121: 10 mg twice daily in people with Nonalcoholic Steatohepatitis, run by Manal Abdelmalek at 8 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 7 Jan 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Analysis of MRI-PDFF Change From Baseline to Week 24 (Per Protocol Population) (time frame: Baseline to week 24). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02442687, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jan 2019.