Study to Evaluate the Safety and Efficacy of ASC42 Tablets in Subjects With Primary Biliary Cholangitis

Study Overview
=================
Brief Summary
-----------------
This study is a phase II, multicenter, randomized, double-blind, placebo-controlled, seamless adaptive design clinical study, aiming to evaluate the safety and effectiveness of three doses of ASC42 matched placebo in subjects with primary biliary cholangitis.

Official Title
-----------------
A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety and Efficacy of ASC42 Tablets in Subjects With Primary Biliary Cholangitis

Conditions
-----------------
Primary Biliary Cholangitis

Intervention / Treatment
-----------------
* Drug: ASC42 5 mg
* Drug: ASC42 10 mg
* Drug: ASC42 15 mg
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age ≥ 18 and ≤75 years old at screening. Definite or probable PBC diagnosis, as demonstrated by the presence of ≥ 2 of the following 3 diagnostic factors: Biochemical evidence of cholestasis based on ALP elevation. Presence of AMA, or other PBC-specific autoantibodies, including sp100 or gp210, if AMA is negative. Liver biopsy consistent with PBC. Screening ALP ≥ 1.67× ULN Taking UDCA for at least 6 months (stable dose for ≥ 3 months) prior to Day 0, or unable to tolerate UDCA (no UDCA for ≥ 3 months) prior to Day 0. Exclusion Criteria: ALT or AST > 5× ULN; ALP >10× ULN History or presence of other concomitant liver diseases Child-Pugh grade B or C

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

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ASC42 tablets of 5mg<br>ASC42 tablets 5mg for 12 weeks | Drug: ASC42 5 mg<br>* 5 mg of ASC42 tablets orally once daily for 12 weeks.<br>|
| Experimental: ASC42 tablets of 10mg<br>ASC42 tablets 10mg for 12 weeks | Drug: ASC42 10 mg<br>* 2 x 5 mg of ASC42 tablets orally once daily for 12 weeks.<br>|
| Experimental: ASC42 tablets of 15mg<br>ASC42 tablets 15mg for 12 weeks | Drug: ASC42 15 mg<br>* 15 mg of ASC42 tablets orally once daily for 12 weeks.<br>|
| Placebo Comparator: Placebo<br>Placebo for 12 weeks | Drug: Placebo<br>* Placebo tablets orally once daily for 12 weeks.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage changes of alkaline phosphatase (ALP) compared with baseline. |  | Day85 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage changes and absolute changes of alkaline phosphatase (ALP) compared with baseline. |  | Day15\29\57\85 | 
| Percentage changes and absolute changes of serum γ-glutamyltransferase (GGT), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) compared with baseline. |  | Day15\29\57\85 | 
| Incidence of treatment-emergent adverse events, serious adverse events and adverse events of special interests. |  | Day15\29\57\85 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
ASC42, primary biliary cholangitis, PBC