Study to Evaluate the Efficacy and Safety of K-877-ER and CSG452 in Participants With NASH With Liver Fibrosis

Study Overview
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Brief Summary
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A study to investigate the use of combination therapy with two investigational products for the treatment of adult patients with Nonalcoholic steatohepatitis (NASH).

Official Title
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Study to Evaluate the Efficacy and Safety of Combination Therapy of K-877-ER and CSG452 in Participants With Noncirrhotic Nonalcoholic Steatohepatitis (NASH) With Liver Fibrosis

Conditions
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NASH

Intervention / Treatment
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* Drug: K-877-ER
* Drug: CSG452
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able to understand and comply with study procedures and give written informed consent Age ≥18 years NAS ≥4 with a score of at least 1 in each component of the NAS (steatosis, lobular inflammation, and ballooning) at Visit 2 liver biopsy, or a historical liver biopsy performed within 24 weeks of randomization Fibrosis stage of 1 or greater and below 4 on NASH CRN (Clinical Research Network) fibrosis staging system at Visit 2 liver biopsy, or a historical liver biopsy performed within 24 weeks of randomization Meet all inclusion criteria outlined in clinical study protocol Exclusion Criteria: Participation in another clinical trial involving an investigational agent within 30 days prior to signing the Informed Consent Form (ICF) for this study Ongoing or recent consumption of Greater than moderate amounts of alcohol as defined in clinical study protocol Evidence of other forms of chronic liver disease as defined in clinical study protocol Does not meet any other exclusion criteria outlined in clinical study protocol

Ages Eligible for Study
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Minimum Age: 18 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: Factorial Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: K-001<br>K-877-ER and CSG452 Once daily (QD) | Drug: K-877-ER<br>* K-877-ER tablet<br>Drug: CSG452<br>* CSG452 tablet<br>|
| Experimental: K-877-ER<br>K-877-ER and CSG452 Placebo QD | Drug: K-877-ER<br>* K-877-ER tablet<br>Drug: Placebo<br>* Placebo tablet<br>|
| Experimental: CSG452<br>CSG452 and K-877-ER Placebo QD | Drug: CSG452<br>* CSG452 tablet<br>Drug: Placebo<br>* Placebo tablet<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo tablet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement in disease activity and no worsening of liver fibrosis (Yes/No) | The improvement in disease activity is defined as decrease in NAFLD Activity Score (NAS) ≥2 points. The worsening of fibrosis is defined as any numerical increase in the stage. | Baseline to Week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment-Related Adverse Events (AE) | Time frame is 52 weeks unless an unresolved AE is still being followed | 52 Weeks |