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A Study to Evaluate the Efficacy and Safety of ALN-HSD in Adult Participants With Non-alcoholic Steatohepatitis (NASH) With Fibrosis With Genetic Risk Factors (NASHGEN-2)

Primary Purpose

Nonalcoholic Steatohepatitis

Status
Recruiting
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
ALN-HSD
Placebo
Sponsored by
Regeneron Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Nonalcoholic Steatohepatitis focused on measuring NASH, NASH with Fibrosis, NAFLD, Non Alcoholic Fatty Liver Disease

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Key Inclusion Criteria:

  1. A diagnosis of NASH with fibrosis (F) stage 2 or 3
  2. NAS score ≥4 according to the NASH CRN histological scoring system
  3. Meets genotype criteria for study enrollment in either Study 1 or Study 2

Key Exclusion Criteria:

  1. Evidence of other forms of known chronic liver disease
  2. Known history of alcohol or other substance abuse within the last year
  3. History of Type 1 diabetes
  4. Bariatric surgery within prior approximately 5 years or planned during the study period
  5. Prior exposure to any investigational drug targeting HSD17B13 or PNPLA3 (eg, ALNHSD or ARO-HSD, AZD2693)

Note: Other protocol-defined Inclusion/Exclusion Criteria apply

Sites / Locations

  • San Fernando Valley Health InstituteRecruiting
  • Velocity Clinical ResearchRecruiting
  • Southern California Research CenterRecruiting
  • Velocity Clinical ResearchRecruiting
  • Velocity Clinical Research - Huntington ParkRecruiting
  • National Research InstituteRecruiting
  • Clinnova Research SolutionsRecruiting
  • National Research InstituteRecruiting
  • Cadena Care Inst.Recruiting
  • Inland Empire Liver FoundationRecruiting
  • Precision Research Institute, LlcRecruiting
  • Miami Clinical Research CenterRecruiting
  • IMIC, IncRecruiting
  • Genoma Research Group, Inc.Recruiting
  • US Associates in Research, LLCRecruiting
  • Med Research Of Florida, LLCRecruiting
  • Legacy Clinical Solutions: Tandem Clinical Research, LLCRecruiting
  • Mercy Medical Center, Inc
  • University of Pennsylvania - Perelman School of Medicine - Gene Therapy ProgramRecruiting
  • Velocity Clinical ResearchRecruiting
  • Allure HealthRecruiting
  • Advanced Medical TrialsRecruiting
  • Pioneer Research Solutions Inc.Recruiting
  • R & H Clinical ResearchRecruiting
  • GLRI - McAllen ResearchRecruiting
  • American Research Corporation at The Texas Liver InstituteRecruiting
  • R & H Clinical ResearchRecruiting
  • JCHO Hokkaido HospitalRecruiting
  • Seoul National University Bundang Hospital (SNUBH)Recruiting
  • Keimyung University Dongsan Medical CenterRecruiting
  • Hanyang University Seoul HospitalRecruiting
  • Klinical InvestigationsRecruiting
  • Latin Clinical Trial CenterRecruiting
  • FDI Clinical ResearchRecruiting
  • ISIS Clinical Research CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Active Comparator

Active Comparator

Placebo Comparator

Active Comparator

Active Comparator

Placebo Comparator

Arm Label

Study 1 ALN-HSD Low Dose

Study 1 ALN-HSD High Dose

Study 1 Placebo

Study 2 ALN-HSD Low Dose

Study 2 ALN-HSD High Dose

Study 2 Placebo

Arm Description

Outcomes

Primary Outcome Measures

Change from baseline in qFibrosis
Study 1 and Study 2 Change in the continuous quantitative liver fibrosis (qFibrosis) score measured by second harmonic generation/two-photon excitation microscopy

Secondary Outcome Measures

Improvement of clinical research network (CRN) fibrosis (F) stage ≥1 stage on liver biopsy without worsening of non-alcoholic steatohepatitis (NASH)
Study 1 and Study 2 Assessment will be based on the proportion of ALN-HSD treated participants relative to placebo achieving at least a 1 stage improvement in fibrosis (NASH Clinical Research Network system) by liver biopsy with no worsening of NAS.
Resolution of NASH with no worsening of fibrosis on liver biopsy
Study 1 and Study 2 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
Change from baseline in serum alanine aminotransferase (ALT)
Study 1 and Study 2
Change from baseline in serum aspartate aminotransferase (AST)
Study 1 and Study 2
Change from baseline in enhanced liver fibrosis (ELF)
Study 1 and Study 2
Change from baseline in N-terminal type III collagen propeptide (PRO-C3)
Study 1 and Study 2
Change from baseline of non-invasive fibrosis biomarkers (NIS-4)
Study 1 and Study 2
Change from baseline in Fibrosis-4 (FIB-4)
Study 1 and Study 2
Change from baseline in hepatic hydroxysteroid 17β dehydrogenase 13 (HSD17B13) transcript level
Study 1 and Study 2
Change from baseline in liver quantitative ballooning (qBallooning)
Study 1 and Study 2
Incidence of progression in qFibrosis on liver biopsy
Study 1 and Study 2
Incidence and severity of treatment emergent adverse events (TEAEs)
Study 1 and Study 2

Full Information

First Posted
August 15, 2022
Last Updated
October 10, 2023
Sponsor
Regeneron Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT05519475
Brief Title
A Study to Evaluate the Efficacy and Safety of ALN-HSD in Adult Participants With Non-alcoholic Steatohepatitis (NASH) With Fibrosis With Genetic Risk Factors
Acronym
NASHGEN-2
Official Title
A Master Protocol of Randomized, Double-Blind, Placebo-Controlled, Phase 2 Studies of siRNA Gene Silencing for the Treatment of Non- Alcoholic Steatohepatitis (NASH) in Participants With Genetic Risk Factors
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 9, 2023 (Actual)
Primary Completion Date
December 9, 2026 (Anticipated)
Study Completion Date
December 9, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Regeneron Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The study is researching an investigational drug called ALN-HSD (called "study drug" in this form). The 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). 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 your 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 ALN-HSD 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 your blood at different times Better understanding of the study drug and NASH

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Nonalcoholic Steatohepatitis
Keywords
NASH, NASH with Fibrosis, NAFLD, Non Alcoholic Fatty Liver Disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Number of Arms is 3 per study and planned enrollment is 150 per study
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
300 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Study 1 ALN-HSD Low Dose
Arm Type
Active Comparator
Arm Title
Study 1 ALN-HSD High Dose
Arm Type
Active Comparator
Arm Title
Study 1 Placebo
Arm Type
Placebo Comparator
Arm Title
Study 2 ALN-HSD Low Dose
Arm Type
Active Comparator
Arm Title
Study 2 ALN-HSD High Dose
Arm Type
Active Comparator
Arm Title
Study 2 Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
ALN-HSD
Intervention Description
Administered by subcutaneous injection (SC)
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Administered by SC injection
Primary Outcome Measure Information:
Title
Change from baseline in qFibrosis
Description
Study 1 and Study 2 Change in the continuous quantitative liver fibrosis (qFibrosis) score measured by second harmonic generation/two-photon excitation microscopy
Time Frame
Baseline to week 52
Secondary Outcome Measure Information:
Title
Improvement of clinical research network (CRN) fibrosis (F) stage ≥1 stage on liver biopsy without worsening of non-alcoholic steatohepatitis (NASH)
Description
Study 1 and Study 2 Assessment will be based on the proportion of ALN-HSD treated participants relative to placebo achieving at least a 1 stage improvement in fibrosis (NASH Clinical Research Network system) by liver biopsy with no worsening of NAS.
Time Frame
Baseline to week 52
Title
Resolution of NASH with no worsening of fibrosis on liver biopsy
Description
Study 1 and Study 2 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
Time Frame
Baseline to week 52
Title
Change from baseline in serum alanine aminotransferase (ALT)
Description
Study 1 and Study 2
Time Frame
Baseline to week 52
Title
Change from baseline in serum aspartate aminotransferase (AST)
Description
Study 1 and Study 2
Time Frame
Baseline to week 52
Title
Change from baseline in enhanced liver fibrosis (ELF)
Description
Study 1 and Study 2
Time Frame
Baseline to week 52
Title
Change from baseline in N-terminal type III collagen propeptide (PRO-C3)
Description
Study 1 and Study 2
Time Frame
Baseline to week 52
Title
Change from baseline of non-invasive fibrosis biomarkers (NIS-4)
Description
Study 1 and Study 2
Time Frame
Baseline to week 52
Title
Change from baseline in Fibrosis-4 (FIB-4)
Description
Study 1 and Study 2
Time Frame
Baseline to week 52
Title
Change from baseline in hepatic hydroxysteroid 17β dehydrogenase 13 (HSD17B13) transcript level
Description
Study 1 and Study 2
Time Frame
Baseline to week 52
Title
Change from baseline in liver quantitative ballooning (qBallooning)
Description
Study 1 and Study 2
Time Frame
Baseline to week 52
Title
Incidence of progression in qFibrosis on liver biopsy
Description
Study 1 and Study 2
Time Frame
Baseline to week 52
Title
Incidence and severity of treatment emergent adverse events (TEAEs)
Description
Study 1 and Study 2
Time Frame
Baseline to week 84

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria: Adult male or female ≥18 years (or country's legal age of adulthood) A diagnosis of NASH with fibrosis (F) stage 2 or 3 NAS score ≥4 according to the NASH CRN histological scoring system Meets genotype criteria for study enrollment in either Study 1 or Study 2, as defined in the protocol A Vibration-Controlled Transient Elastography (VCTE) liver stiffness measurement, as defined in the protocol Key Exclusion Criteria: Evidence of other forms of known chronic liver disease Known history of alcohol or other substance abuse within the last year 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 PNPLA3 (eg, ALNHSD or ARO-HSD, AZD2693) Note: Other protocol-defined Inclusion/Exclusion Criteria apply
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Clinical Trials Administrator
Phone
844-734-6643
Email
clinicaltrials@regeneron.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trial Management
Organizational Affiliation
Regeneron Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
San Fernando Valley Health Institute
City
Canoga Park
State/Province
California
ZIP/Postal Code
91034
Country
United States
Individual Site Status
Recruiting
Facility Name
Velocity Clinical Research
City
Chula Vista
State/Province
California
ZIP/Postal Code
91911
Country
United States
Individual Site Status
Recruiting
Facility Name
Southern California Research Center
City
Coronado
State/Province
California
ZIP/Postal Code
92118
Country
United States
Individual Site Status
Recruiting
Facility Name
Velocity Clinical Research
City
Gardena
State/Province
California
ZIP/Postal Code
90247
Country
United States
Individual Site Status
Recruiting
Facility Name
Velocity Clinical Research - Huntington Park
City
Huntington Park
State/Province
California
ZIP/Postal Code
90255
Country
United States
Individual Site Status
Recruiting
Facility Name
National Research Institute
City
Los Angeles
State/Province
California
ZIP/Postal Code
90057
Country
United States
Individual Site Status
Recruiting
Facility Name
Clinnova Research Solutions
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Individual Site Status
Recruiting
Facility Name
National Research Institute
City
Panorama City
State/Province
California
ZIP/Postal Code
91402
Country
United States
Individual Site Status
Recruiting
Facility Name
Cadena Care Inst.
City
Poway
State/Province
California
ZIP/Postal Code
92064
Country
United States
Individual Site Status
Recruiting
Facility Name
Inland Empire Liver Foundation
City
Rialto
State/Province
California
ZIP/Postal Code
92377
Country
United States
Individual Site Status
Recruiting
Facility Name
Precision Research Institute, Llc
City
San Diego
State/Province
California
ZIP/Postal Code
92114
Country
United States
Individual Site Status
Recruiting
Facility Name
Miami Clinical Research Center
City
Miami
State/Province
Florida
ZIP/Postal Code
33155
Country
United States
Individual Site Status
Recruiting
Facility Name
IMIC, Inc
City
Miami
State/Province
Florida
ZIP/Postal Code
33157
Country
United States
Individual Site Status
Recruiting
Facility Name
Genoma Research Group, Inc.
City
Miami
State/Province
Florida
ZIP/Postal Code
33173
Country
United States
Individual Site Status
Recruiting
Facility Name
US Associates in Research, LLC
City
Miami
State/Province
Florida
ZIP/Postal Code
33175
Country
United States
Individual Site Status
Recruiting
Facility Name
Med Research Of Florida, LLC
City
Miami
State/Province
Florida
ZIP/Postal Code
33186
Country
United States
Individual Site Status
Recruiting
Facility Name
Legacy Clinical Solutions: Tandem Clinical Research, LLC
City
Marrero
State/Province
Louisiana
ZIP/Postal Code
70072
Country
United States
Individual Site Status
Recruiting
Facility Name
Mercy Medical Center, Inc
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21202-2102
Country
United States
Individual Site Status
Withdrawn
Facility Name
University of Pennsylvania - Perelman School of Medicine - Gene Therapy Program
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Individual Site Status
Recruiting
Facility Name
Velocity Clinical Research
City
Cedar Park
State/Province
Texas
ZIP/Postal Code
78613
Country
United States
Individual Site Status
Recruiting
Facility Name
Allure Health
City
Friendswood
State/Province
Texas
ZIP/Postal Code
77546-5700
Country
United States
Individual Site Status
Recruiting
Facility Name
Advanced Medical Trials
City
Georgetown
State/Province
Texas
ZIP/Postal Code
78745
Country
United States
Individual Site Status
Recruiting
Facility Name
Pioneer Research Solutions Inc.
City
Houston
State/Province
Texas
ZIP/Postal Code
77099
Country
United States
Individual Site Status
Recruiting
Facility Name
R & H Clinical Research
City
Katy
State/Province
Texas
ZIP/Postal Code
77494
Country
United States
Individual Site Status
Recruiting
Facility Name
GLRI - McAllen Research
City
Pharr
State/Province
Texas
ZIP/Postal Code
78577
Country
United States
Individual Site Status
Recruiting
Facility Name
American Research Corporation at The Texas Liver Institute
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78215
Country
United States
Individual Site Status
Recruiting
Facility Name
R & H Clinical Research
City
Stafford
State/Province
Texas
ZIP/Postal Code
77477
Country
United States
Individual Site Status
Recruiting
Facility Name
JCHO Hokkaido Hospital
City
Sapporo
State/Province
Hokkaido
ZIP/Postal Code
062 8618
Country
Japan
Individual Site Status
Recruiting
Facility Name
Seoul National University Bundang Hospital (SNUBH)
City
Seongnam-si
State/Province
Gyeonggi-do
ZIP/Postal Code
13620
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Name
Keimyung University Dongsan Medical Center
City
Daegu
ZIP/Postal Code
42601
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Name
Hanyang University Seoul Hospital
City
Seoul
ZIP/Postal Code
04763
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Name
Klinical Investigations
City
San Juan
ZIP/Postal Code
00909
Country
Puerto Rico
Individual Site Status
Recruiting
Facility Name
Latin Clinical Trial Center
City
San Juan
ZIP/Postal Code
00909
Country
Puerto Rico
Individual Site Status
Recruiting
Facility Name
FDI Clinical Research
City
San Juan
ZIP/Postal Code
00927
Country
Puerto Rico
Individual Site Status
Recruiting
Facility Name
ISIS Clinical Research Center
City
San Juan
ZIP/Postal Code
00969
Country
Puerto Rico
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing
IPD Sharing Time Frame
When Regeneron has received marketing authorization from major health authorities (e.g., FDA, European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), etc.) for the product and indication, has made the study results publicly available (e.g., scientific publication, scientific conference, clinical trial registry), has the legal authority to share the data, and has ensured the ability to protect participant privacy.
IPD Sharing Access Criteria
Qualified researchers can submit a proposal for access to individual patient or aggregate level data from a Regeneron-sponsored clinical trial through Vivli. Regeneron's Independent Research Request Evaluation Criteria can be found at: https://www.regeneron.com/sites/default/files/Regeneron-External-Data-Sharing-Policy-and-Independent-Research-Request-Evaluation-Criteria.pdf
IPD Sharing URL
https://vivli.org/

Learn more about this trial

A Study to Evaluate the Efficacy and Safety of ALN-HSD in Adult Participants With Non-alcoholic Steatohepatitis (NASH) With Fibrosis With Genetic Risk Factors

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