A Precision Medicine Approach Using Gene Silencing to Treat a Chronic Liver Disease Called Non-Alcoholic Steatohepatitis (NASH) in Adult Participants at Increased Genetic Risk for This Condition

Non-alcoholic Steatohepatitis (NASH) Clinical Trial

— NASHGEN-2  

Official title:

A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study of siRNA Gene Silencing for the Treatment of Non- Alcoholic Steatohepatitis (NASH) in Participants With Genetic Risk Factors

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05519475
• Other study ID #: ALN-HSD-NASH-2130
• Status: Recruiting
• Phase: Phase 2
• Start date: February 9, 2023
• Est. completion date: September 8, 2027

Study information

• Verified date: April 2024
• Source: Regeneron Pharmaceuticals
• Contact: Clinical Trials Administrator
• Phone: 844-734-6643
• Email: clinicaltrials[@]regeneron.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is researching an investigational drug called ALN-HSD (called "study drug"). This study is focused on participants who are known to have non-alcoholic steatohepatitis (NASH). NASH is a form of non-alcoholic fatty liver disease (NAFLD). Recently, the name metabolic dysfunction associated steatohepatitis (MASH) has been introduced to replace NASH and metabolic dysfunction-associated steatotic liver disease (MASLD) to replace NAFLD. NASH occurs when fat builds up in liver cells, damaging them, and making the liver inflamed and stiff from fibrosis (scar tissue). NASH 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 NASH.

The study is looking at several other research questions, including:

• How the study drug works to improve liver function and lessen NASH 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 NASH

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: September 8, 2027
• Est. primary completion date: September 8, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Key Inclusion Criteria:

1. Adult male or female =18 years (or country's legal age of adulthood)

2. A diagnosis of NASH with fibrosis (F) stage 2 or 3

3. NAS score =4 according to the NASH CRN histological scoring system

4. Meets genotype criteria for study enrollment, as defined in the protocol

Key Exclusion Criteria:

1. Evidence of other forms of known chronic liver disease, as defined in the protocol

2. Known history of alcohol or other substance abuse within the last year or at any time during screening

3. History of Type 1 diabetes

4. Bariatric surgery within approximately 5 years prior to or planned during the study period

5. Prior exposure to any investigational drug targeting HSD17B13 or patatin-like phospholipase domain containing 3 (PNPLA3) (eg, ALN-HSD or ARO-HSD, AZD2693)

Note: Other protocol-defined Inclusion/Exclusion Criteria apply

Related Conditions & MeSH terms

• Fatty Liver
• Liver Diseases
• Non-alcoholic Fatty Liver Disease
• Non-alcoholic Steatohepatitis (NASH)

Intervention

Drug:
• ALN-HSD
Administered by subcutaneous injection (SC)
• Placebo
Administered by SC injection

Locations

Country	Name	City	State
Japan	JCHO Hokkaido Hospital	Sapporo	Hokkaido
Korea, Republic of	Keimyung University Dongsan Hospital	Daegu
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si	Gyeonggi-do
Korea, Republic of	Hanyang University Seoul Hospital	Seoul
Puerto Rico	ISIS Clinical Research Center	Guaynabo
Puerto Rico	FDI Clinical Research	San Juan
Puerto Rico	Klinical Investigations	San Juan
Puerto Rico	Latin Clinical Trial Center	San Juan
United States	Mercy Medical Center	Baltimore	Maryland
United States	San Fernando Valley Health Institute	Canoga Park	California
United States	Velocity Clinical Research - Austin	Cedar Park	Texas
United States	Velocity Clinical Research	Chula Vista	California
United States	Southern California Research Center	Coronado	California
United States	Allure Health at Mt. Olympus Medical Research	Friendswood	Texas
United States	Velocity Clinical Research	Gardena	California
United States	Advanced Medical Trials	Georgetown	Texas
United States	Pioneer Research Solutions, Inc.	Houston	Texas
United States	Velocity Clinical Research - Huntington Park	Huntington Park	California
United States	R & H Clinical Research, Inc.	Katy	Texas
United States	Velocity Clinical Research - Westlake	Los Angeles	California
United States	Tandem Clinical Research	Marrero	Louisiana
United States	Genoma Research Group, Inc.	Miami	Florida
United States	IMIC, Inc	Miami	Florida
United States	Med Research of Florida, LLC	Miami	Florida
United States	Miami Clinical Research Center	Miami	Florida
United States	US Associates in Research, LLC	Miami	Florida
United States	Clinnova Research Solutions	Orange	California
United States	National Research Institute	Panorama City	California
United States	GLRI - McAllen Research	Pharr	Texas
United States	University of Pennsylvania - Perelman School of Medicine - Gene Therapy Program	Philadelphia	Pennsylvania
United States	Cadena Care Inst.	Poway	California
United States	Inland Empire Liver Foundation	Rialto	California
United States	American Research Corporation at The Texas Liver Institute	San Antonio	Texas
United States	Precision Research Institute - San Diego	San Diego	California
United States	R & H Clinical Research	Stafford	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Regeneron Pharmaceuticals

Countries where clinical trial is conducted

United States,  Japan,  Korea, Republic of,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in qFibrosis	Change in the continuous quantitative liver fibrosis (qFibrosis) score measured by second harmonic generation/two-photon excitation microscopy	Baseline to week 52
Secondary	Improvement of non-alcoholic steatohepatitis clinical research network (NASH-CRN) fibrosis (F) stage by =1 stage without worsening of NASH	Assessment will be based on the proportion of ALN-HSD treated participants relative to placebo achieving at least a 1 stage improvement in fibrosis by liver biopsy with no worsening of NASH	Baseline to week 52
Secondary	Resolution of NASH with no worsening of NASH-CRN fibrosis on liver biopsy	Resolution of NASH (steatohepatitis) is defined as absent fatty liver disease or isolated or simple steatosis without steatohepatitis and a non-alcoholic fatty liver disease activity score (NAS) score of 0-1 for inflammation, 0 for ballooning, and any value for steatosis	Baseline to week 52
Secondary	Change in serum alanine aminotransferase (ALT)		Baseline to week 52
Secondary	Change in serum aspartate aminotransferase (AST)		Baseline to week 52
Secondary	Change in enhanced liver fibrosis (ELF)		Baseline to week 52
Secondary	Change in N-terminal type III collagen propeptide (PRO-C3)		Baseline to week 52
Secondary	Change in NIS4, a non-invasive fibrosis biomarker of NASH		Baseline to week 52
Secondary	Change in Fibrosis-4 (FIB-4)		Baseline to week 52
Secondary	Change in hepatic hydroxysteroid 17ß dehydrogenase 13 (HSD17B13) transcript level		Baseline to week 52
Secondary	Incidence of progression in qFibrosis on liver biopsy		Baseline to week 52
Secondary	Incidence of treatment-emergent adverse events (TEAEs)		Baseline to week 84
Secondary	Severity of treatment-emergent adverse events (TEAEs)		Baseline to week 84