NCT05519475
Recruiting
Phase 2
A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study of siRNA Gene Silencing for the Treatment of Metabolic Dysfunction-Associated Steatohepatitis (MASH) in Participants With Genetic Risk Factors
Regeneron Pharmaceuticals135 sites in 1 country90 target enrollmentStarted: February 9, 2023Last updated:
Overview
- Phase
- Phase 2
- Status
- Recruiting
- Sponsor
- Regeneron Pharmaceuticals
- Enrollment
- 90
- Locations
- 135
- Primary Endpoint
- Change in qFibrosis
Overview
Brief Summary
This study is researching an investigational drug, ALN-HSD called "study drug". This study is focused on participants who are known to have metabolic dysfunction-associated steatohepatitis (MASH). MASH is a form of metabolic dysfunction-associated steatotic liver disease (MASLD). MASH occurs when fat builds up in liver cells, damaging them, and making the liver inflamed and stiff from fibrosis (scar tissue). MASH can progress to cirrhosis (long term scarring) and liver failure (when the liver cannot perform its job). The aim of the study is to see the effect of the study drug on lessening liver scarring side effects related to MASH.
The study is looking at several other research questions, including:
- How ALN-HSD works to improve liver function and lessen MASH-related inflammation in the liver
- What side effects may happen from receiving the study drug
- How much study drug and study drug metabolites (byproduct of the body breaking down the study drug) are in the blood at different times
- Better understanding of the study drug and MASH
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Adult male or female ≥18 years (or country's legal age of adulthood)
- •A diagnosis of MASH with fibrosis (F) stage 2 or 3, according to the NASH-Clinical Research Network (CRN)
- •NAS score ≥3, as defined in the protocol
- •Meets genotype criteria for study enrollment, as defined in the protocol
- •Has protocol defined FibroScan®-AST (FAST) score at screening or within approximately 12 weeks of screening
Exclusion Criteria
- •Evidence of other forms of known chronic liver disease, as defined in the protocol
- •Known history of alcohol or other substance abuse within the last year or at any time during screening, as defined in the protocol
- •History of Type 1 diabetes
- •Bariatric surgery within approximately 5 years prior to or planned during the study period
- •Prior exposure to any investigational drug targeting HSD17B13 or patatin-like phospholipase domain containing 3 (PNPLA3) (eg, ALN-HSD, ARO-HSD, ALN-PNP, AZD2693)
- •Note: Other protocol-defined Inclusion/Exclusion Criteria apply
Arms & Interventions
Placebo
Placebo Comparator
Randomized 1:1
Intervention: Placebo (Drug)
ALN-HSD
Experimental
Randomized 1:1
Intervention: ALN-HSD (Drug)
Outcomes
Primary Outcomes
Change in qFibrosis
Time Frame: Baseline to week 52
Change in the continuous quantitative liver fibrosis (qFibrosis) score measured by second harmonic generation/two-photon excitation microscopy
Secondary Outcomes
- Change in enhanced liver fibrosis (ELF)(Baseline to week 52)
- Change in serum aspartate aminotransferase (AST)(Baseline to week 52)
- Improvement of non-alcoholic steatohepatitis clinical research network (NASH-CRN) fibrosis (F) stage by ≥1 stage without worsening of MASH on liver biopsy(Baseline to week 52)
- Resolution of MASH with no worsening of NASH-CRN fibrosis on liver biopsy(Baseline to week 52)
- Change in serum alanine aminotransferase (ALT)(Baseline to week 52)
- Change in N-terminal type III collagen propeptide (PRO-C3)(Baseline to week 52)
- Change in NIS4, a non-invasive fibrosis biomarker of NASH(Baseline to week 52)
- Change in Fibrosis-4 (FIB-4)(Baseline to week 52)
- Change in hepatic hydroxysteroid 17β dehydrogenase 13 (HSD17B13) transcript level(Baseline to week 52)
- Incidence of progression in qFibrosis on liver biopsy(Baseline to week 52)
- Incidence of treatment-emergent adverse events (TEAEs)(Baseline to week 84)
- Severity of treatment-emergent adverse events (TEAEs)(Baseline to week 84)
Investigators
Study Sites (135)
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