A Study to Assess the Efficacy and Safety of VK2809 for 52 Weeks in Subjects With Biopsy Proven NASH

Study Overview
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Brief Summary
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The study includes 52 weeks, double-blind treatment period. Clinic visits will occur at Randomization and every four weeks from Week 4 through Week 52 and through End of Study period. The study includes a post-dosing study visit that will occur 4 weeks after the last dose of study drug. This visit represents the End-of-Study Visit (Week 56 Visit). Three hundred thirty-seven subjects will be enrolled into five treatment arms and there will be an equal distribution of males and females in each treatment arm. Subjects will be stratified by gender, fibrosis stage, and diabetes status.

Official Title
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VK2809 A Phase 2B, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Assess the Efficacy, Safety, and Tolerability of VK2809 Administered for 52 Weeks Followed by a 4-Week Off-Drug Phase in Subjects With Biopsy Proven Non-Alcoholic Steatohepatitis With Fibrosis

Conditions
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NASH - Nonalcoholic Steatohepatitis

Intervention / Treatment
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* Drug: VK2809
* Drug: Placebos


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provide a personally signed and dated informed consent document indicating that the subject (or a legally acceptable representative) has been informed of all pertinent aspects of the study and is willing and able to participate; Have a histologically-confirmed diagnosis of NASH on a liver biopsy performed during screening or within 6 months before screening; for this study, confirmation requires: NASH Clinical Research Network (CRN) fibrosis stage 1 to stage 3 and NASH activity score (NAS) of ≥4 with at least a score of 1 in each of the following NAS components: ballooning degeneration (score = 0-2), lobular inflammation (score = 0-3) and steatosis (score = 0-3); (c) F1 subjects must have at least one of these risk factors: type 2 diabetes, body mass index of ≥ 30 mg/ m2, and/ or alanine aminotransferase > 1.5 x ULN Have a screening MRI-PDFF with ≥ 8% liver fat fraction; Male and females be 18 to 75 years of age, inclusive, at screening; Exclusion Criteria: Are unwilling to undergo the required liver biopsy procedures or have any condition that would prevent obtaining a liver biopsy as part of this clinical protocol Have evidence of current or history of excessive alcohol consumption of more than 20 g per day for women and 30 g per day for men, on average, within 6 months before the qualifying liver biopsy and up to randomization, or are unable to provide a reliable estimate of alcohol consumption during this period; Treatment with medications for the purpose of weight loss within 6 months prior to qualifying liver biopsy, unless approved after consultation with the medical monitor. These include drugs approved for weight loss (e.g. orlistat, bupropion/naltrexone, phentermine-topiramate, phentermine, lorcaserin), as well as drugs used off-label, herbal preparations and dietary supplements marketed for control of body weight or appetite; TSH outside central laboratory reference range; Free T4 outside central laboratory reference range; Cardiac troponin I (cTnI) and creatine kinase MB isoenzyme (CK-MB) > Upper Limit of Normal (ULN) at screening; Serum albumin < 3.5 g/dL; International normalized ratio (INR) > 1.3; Total bilirubin > 1.2 X ULN (except in presence of Gilbert synd Strong or moderate inhibitors or inducers of CYP3A4 are prohibited during the study period Drugs that may affect liver fat content or are associated with nonalcoholic fatty liver disease (NAFLD) are prohibited during the 3 month period prior to the baseline liver biopsy and up to the end of treatment

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Drug: Placebos<br>* Capsule<br>|
| Experimental: 1.0 mg<br> | Drug: VK2809<br>* Capsule<br>|
| Experimental: 2.5mg<br> | Drug: VK2809<br>* Capsule<br>|
| Experimental: 5.0 mg<br> | Drug: VK2809<br>* Capsule<br>|
| Experimental: 10 mg<br> | Drug: VK2809<br>* Capsule<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Liver Fat | Relative change in liver fat content (assessed by MRI-PDFF) from baseline to Week 12 in subjects treated with VK2809 compared to the change in subjects treated with placebo. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| NASH CRN fibrosis score | Proportion of subjects with resolution of steatohepatitis on overall histopathological reading and no worsening of liver fibrosis on NASH CRN fibrosis score. | 52 weeks |