Nash
Conditions
Keywords
efficacy, safety, HSD17β13
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.
Interventions
DRUGVSA006
every 12 weeks, subcutaneous injections
DRUGPlacebo
every 12 weeks, subcutaneous injections
Sponsors
Visirna Therapeutics HK Limited
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
| 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 | — |
| Time of maximum concentration of VSA006 (Tmax) | Pre-dose, 0.5, 1, 2, 4, 8, 12 and 24 hours post dose | — |
| anti-drug antibodies (ADAs) of VSA006 | up to week 82 | — |
| Compared with placebo, the percentage change in serum alanine aminotransferase (ALT) | At week 24, week 52 and week 82 | — |
Countries
China
Outcome results
None listed