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

Phase 2Not Yet RecruitingNCT06322628

Visirna Therapeutics HK Limited45 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Nash

Interventions

VSA006

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

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;

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: At week 52

Secondary Outcomes

Compared with placebo, the percentage change in serum alanine aminotransferase (ALT)

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: 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

Time frame: At week 52

Incidence and severity of adverse events (AEs) and serious adverse events (SAEs), and their correlation with VSA006

Time frame: Up to week 82

Maximum observed concentration (Cmax) of VSA006

Time frame: Pre-dose, 0.5, 1, 2, 4, 8, 12 and 24 hours post dose

Time of maximum concentration of VSA006 (Tmax)

Time frame: 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

Time frame: Pre-dose, 0.5, 1, 2, 4, 8, 12 and 24 hours post dose

anti-drug antibodies (ADAs) of VSA006

Time frame: up to week 82