A Phase 2 Clinical Trial to Evaluate the Efficacy and Safety of VSA006 in Chinese NASH Patients

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase II Clinical Trial to Evaluate the Efficacy and Safety of VSA006 Injection in Chinese Adult Patients With Nonalcoholic Steatohepatitis (NASH)

Human genetic studies have shown that loss of function (LOF) mutations in HSD17β13 gene have a protective effect on the progression of alcohol-related and non-alcohol-related liver diseases, such as NASH, without significant adverse phenotypes.

VSA006 is a siRNA drug targeting HSD17β13 mRNA in the liver and reduce the protein level of HSD17β13. Based on phase 1 study results in healthy volunteers and NASH/suspected NASH patients, this phase 2 study is designed to evaluate the efficacy, safety, PK profiles and immunogenicity of VSA006 in Chinese NASH patients.

Study Overview

• Status: Not yet recruiting
• Conditions: Nash
• Intervention / Treatment: Drug: VSA006; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 45
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• body mass index (BMI) of 24-35 kg/m2 ;
• NASH patients confirmed by liver histopathology: NAS score is ≥ 4 and CRN fibrosis is F2 or F3 ;
• At screening, ALT is > ULN;
• At screening, the liver fat content measured by MRI-PDFF is ≥ 8%;
• Weight change < 5% at least 3 months prior to screening;
• For patient with T2DM, the hypoglycemic agents and HbA1c is stable

Exclusion Criteria:

• Pregnant or lactating women;
• Previous diagnosis of alcoholic liver disease or hepatitis/liver disease due to other causes;
• Previous or current diagnosis of cirrhosis or decompensated cirrhosis;
• Previous or current diagnosis of hyperthyroidism, hypothyroidism, or other diseases that can lead to fatty degeneration of liver;
• Participants diagnosed with type 1 diabetes, or with unstable type 2 diabetes
• Participants who cannot receive an MRI examination;

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: VSA006 low dose	Drug: VSA006; every 12 weeks, subcutaneous injections
Placebo Comparator: VSA006 low dose comparator	Drug: Placebo; every 12 weeks, subcutaneous injections
Experimental: VSA006 high dose	Drug: VSA006; every 12 weeks, subcutaneous injections
Placebo Comparator: VSA006 high dose comparator	Drug: Placebo; every 12 weeks, subcutaneous injections

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Achieving ≥ 1 Stage Improvement in Histological Fibrosis with no Worsening of NASH	No Worsening of NASH is defined as no increase in inflammation, ballooning, or steatosis scores in the NAS score.	At week 52
Percentage of Participants Achieving NASH Improvement with no Worsening of Fibrosis	NASH Improvement indicates a reduction by at least 2 points in the NAS score, with at least one-point reduction in ballooning without increase in steatosis score.	At week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Compared with placebo, the percentage change in serum alanine aminotransferase (ALT)		At week 24, week 52 and week 82
Compared with placebo, the change in liver fat fraction from baseline and liver fat percentage change from baseline	measured by magnetic resonance imaging-proton density fat fraction (MRI-PDFF)	At week 24 and week 52
Compared with placebo, the percentage of participants with a > 30% decrease in liver fat fraction from baseline	measured by magnetic resonance imaging-proton density fat fraction (MRI-PDFF)	At week 24 and week 52
Compared with placebo, the change and percentage change in noninvasive markers of fibrosis from baseline: FIB-4, NAFLD fibrosis score, and AST/PLT ratio index (APRI)		At week 24, week 52 and week 82
Percentage of Participants Achieving NASH Resolution with no Worsening of Fibrosis	NASH resolution was defined as a NAS score of 0-1 for inflammation, 0 for ballooning, and no increase in steatosis score	At week 52
Incidence and severity of adverse events (AEs) and serious adverse events (SAEs), and their correlation with VSA006		Up to week 82
Maximum observed concentration (Cmax) of VSA006		Pre-dose, 0.5, 1, 2, 4, 8, 12 and 24 hours post dose
Time of maximum concentration of VSA006 (Tmax)		Pre-dose, 0.5, 1, 2, 4, 8, 12 and 24 hours post dose
Area under the concentration-time curve from time zero (pre-dose) to the last quantifiable concentration (AUC0-t) of VSA006		Pre-dose, 0.5, 1, 2, 4, 8, 12 and 24 hours post dose
anti-drug antibodies (ADAs) of VSA006		up to week 82

Collaborators and Investigators

• Sponsor: Visirna Therapeutics HK Limited

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2024
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): July 1, 2026

Study Registration Dates

• First Submitted: December 22, 2023
• First Submitted That Met QC Criteria: March 13, 2024
• First Posted (Actual): March 21, 2024

Study Record Updates

• Last Update Posted (Actual): March 21, 2024
• Last Update Submitted That Met QC Criteria: March 13, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: safety; efficacy; HSD17β13
• Other Study ID Numbers: VSA006-2001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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