A Phase 2 Clinical Trial to Evaluate the Efficacy and Safety of VSA006 in Chinese NASH Patients
- Registration Number
- NCT06322628
- Lead Sponsor
- Visirna Therapeutics HK Limited
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 45
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description VSA006 high dose comparator Placebo - VSA006 low dose VSA006 - VSA006 low dose comparator Placebo - VSA006 high dose VSA006 -
- Primary Outcome Measures
Name Time Method Percentage of Participants Achieving ≥ 1 Stage Improvement in Histological Fibrosis with no Worsening of NASH At week 52 No Worsening of NASH is defined as no increase in inflammation, ballooning, or steatosis scores in the NAS score.
Percentage of Participants Achieving NASH Improvement with no Worsening of Fibrosis At week 52 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.
- Secondary Outcome Measures
Name Time Method 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 At week 24 and week 52 measured by magnetic resonance imaging-proton density fat fraction (MRI-PDFF)
Compared with placebo, the percentage of participants with a > 30% decrease in liver fat fraction from baseline At week 24 and week 52 measured by magnetic resonance imaging-proton density fat fraction (MRI-PDFF)
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 At week 52 NASH resolution was defined as a NAS score of 0-1 for inflammation, 0 for ballooning, and no increase in steatosis score
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