Study to Evaluate the Safety, Tolerability, and Efficacy of ASC41 Tablets in Adult Patients With NASH

A Phase II, Double-Blind, Randomized, Multicenter, Placebo-controlled Study to Evaluate the Safety, Tolerability, and Efficacy of ASC41 in Subjects With Nonalcoholic Steatohepatitis (NASH)

This is a Phase 2, Double-Blind, Randomized, Multicenter, Placebo-controlled Study to Evaluate the Safety, Tolerability, and Efficacy of ASC41 in Adults with Nonalcoholic Steatohepatitis (NASH).

Study Overview

• Status: Recruiting
• Conditions: Non-alcoholic Fatty Liver Disease; Non-alcoholic Steatohepatitis
• Intervention / Treatment: Drug: 2mg of ASC41; Drug: Placebo; Drug: 4mg of ASC41 (2 tablets of 2 mg ASC41)

• Study Type: Interventional
• Enrollment (Estimated): 180
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Junping Shi, Doctor; Phone Number: 13957121199; Email: 13957121199@vip.126.com
• Study Contact Backup: Name: ling Gong, Doctor; Phone Number: 13777384503; Email: 13777384503@163.com

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310000
      • Recruiting
      • The Affiliated Hospital of Hangzhou Normal University
      • Contact: Junping Shi, Doctor; Phone Number: +86-13957121199; Email: 13957121199@vip.126.com
      • Contact: ling Gong, Doctor; Phone Number: +86-13777384503; Email: 13777384503@163.com
      • Principal Investigator: Junping Shi, Doctor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 18 and ≤ 80 years old at screening.
• Presence of ≥ 7.5% steatosis on screening MRI-PDFF read centrally by a radiologist and performed either during the screening period or within 6 months prior to the first visit.
• HbA1c ≤ 9.5%.
• Normal or minimally abnormal renal function as defined by estimated glomerular filtration rate (eGFR) ≥ 50 mL/min/1.73 m^2

Exclusion Criteria:

• Presence or history of cirrhosis or evidence of decompensated liver disease (e.g., ascites, variceal bleeding) or hepatocellular carcinoma.
• History or presence of other concomitant liver disease as assessed by the investigator or determined by laboratory findings.
• Uncontrolled Type 2 diabetes mellitus (T2DM) defined as HbA1c of > 9.5% within 60 days prior to enrollment.
• Change in anti-diabetic therapy within 6 months prior to qualifying liver biopsy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1 Low Dose; 1 tablet of ASC41 (2 mg) for 52 weeks	Drug: 2mg of ASC41; ASC41 tablet administered orally once daily.; Drug: Placebo; Placebo tablets administered orally once daily.
Experimental: Cohort 2 High Dose; 2 tablet of ASC41 (4 mg) for 52 weeks	Drug: 4mg of ASC41 (2 tablets of 2 mg ASC41); ASC41 tablets administered orally once daily.
Placebo Comparator: Placebo tablet; Placebo tablet for 52 weeks	Drug: Placebo; Placebo tablets administered orally once daily.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the effect of ASC41 compared with placebo in noncirrhotic subjects with NASH by a histological change.	A histological change in NAFLD (nonalcoholic fatty liver disease) Activity Score (NAS) ≥ 2 points that results from reduction of necroinflammation (inflammation or ballooning) without worsening fibrosis. (The NAFLD Activity Score including steatosis, inflammation and ballooning. The maximum score of steatosis was 3 and the minimum score was 0, the maximum score of inflammation was 3 and the minimum score was 0, and the maximum score of ballooning was 2 and the minimum score was 0. The higher scores mean a worse outcome. ）	Baseline and Week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The incidence, type and severity of AEs/SAEs were assessed by CTCAE v5.0 to assess the safety and tolerability of ASC41 compared to placebo		24 and 52 weeks
Change from baseline in hepatic fat fraction assessed by MRI-PDFF		24 and 52 weeks
To evaluate the effect of ASC41 compared with placebo on serum lipids (cholesterol, HDL-C, LDL-C, triglycerides, Lp(a), VLDL)		12, 24 and 52 weeks
Plasma pharmacokinetics - Peak Plasma Concentration (Cmax)	Measured after administration	1 and 15 Days
Plasma pharmacokinetics - Area under the plasma drug concentration versus time curve( AUC0-t_, AUC0-∞)		1 and 15 Days
Plasma pharmacokinetics - The amount of time that a drug is present at the maximum concentration in serum(Tmax)		1 and 15 Days

Collaborators and Investigators

• Sponsor: Gannex Pharma Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): September 30, 2022
• Primary Completion (Estimated): May 10, 2025
• Study Completion (Estimated): June 10, 2025

Study Registration Dates

• First Submitted: July 7, 2022
• First Submitted That Met QC Criteria: July 13, 2022
• First Posted (Actual): July 18, 2022

Study Record Updates

• Last Update Posted (Actual): April 3, 2024
• Last Update Submitted That Met QC Criteria: April 2, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: NASH; Phase II; ASC41; Non-alcoholic Fatty Liver Disease; THR-β
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: ASC41-202

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No