Clinical trial NCT06322628: A Phase 2 Clinical Trial to Evaluate the Efficacy and Safety of VSA006 in Chinese NASH Patients
Official title: 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)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Nash
Keywords: efficacy
safety
HSD17β13
Lead sponsor: Visirna Therapeutics HK Limited
Sponsor class: INDUSTRY
First posted: 2024-03-21
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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;

Primary outcomes:
measure: Percentage of Participants Achieving ≥ 1 Stage Improvement in Histological Fibrosis with no Worsening of NASH
timeFrame: At week 52
measure: Percentage of Participants Achieving NASH Improvement with no Worsening of Fibrosis
timeFrame: At week 52
Secondary outcomes:
measure: Compared with placebo, the percentage change in serum alanine aminotransferase (ALT)
timeFrame: At week 24, week 52 and week 82
measure: Compared with placebo, the change in liver fat fraction from baseline and liver fat percentage change from baseline
timeFrame: At week 24 and week 52
measure: Compared with placebo, the percentage of participants with a > 30% decrease in liver fat fraction from baseline
timeFrame: At week 24 and week 52
measure: 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)
timeFrame: At week 24, week 52 and week 82
measure: Percentage of Participants Achieving NASH Resolution with no Worsening of Fibrosis
timeFrame: At week 52
measure: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs), and their correlation with VSA006
timeFrame: Up to week 82
measure: Maximum observed concentration (Cmax) of VSA006
timeFrame: Pre-dose, 0.5, 1, 2, 4, 8, 12 and 24 hours post dose
measure: Time of maximum concentration of VSA006 (Tmax)
timeFrame: Pre-dose, 0.5, 1, 2, 4, 8, 12 and 24 hours post dose
measure: Area under the concentration-time curve from time zero (pre-dose) to the last quantifiable concentration (AUC0-t) of VSA006
timeFrame: Pre-dose, 0.5, 1, 2, 4, 8, 12 and 24 hours post dose
measure: anti-drug antibodies (ADAs) of VSA006
timeFrame: up to week 82
Other outcomes:
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