Study to Evaluate ALN-CIDEB in Adults With Fibrotic Metabolic Dysfunction-Associated Steatohepatitis (MASH)

A Phase 2b, Randomized, Double-Blind, Placebo-Controlled Study of ALN-CIDEB in Adults With Fibrotic Metabolic Dysfunction-Associated Steatohepatitis (MASH)

This study will test a Regeneron study drug called ALN-CIDEB to find out whether it may help treat a liver disease called MASH.

In this study, researchers are looking at the effect of ALN-CIDEB on reducing liver fat, liver injury, and liver scarring. The study will compare ALN-CIDEB with placebo to understand how well ALN-CIDEB works to lower the amount of fat in the liver.

The study is looking at:

• What side effects ALN-CIDEB might cause
• How well ALN-CIDEB works to change liver fat, liver injury, and liver scarring
• How the body and the liver change after having ALN-CIDEB, which can help researchers understand why ALN-CIDEB works better for some people than others

Study Overview

• Status: Not yet recruiting
• Conditions: Metabolic Dysfunction-Associated Steatohepatitis (MASH)
• Intervention / Treatment: Drug: Placebo; Drug: ALN-CIDEB

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Clinical Trials Administrator; Phone Number: 844-734-6643; Email: clinicaltrials@regeneron.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

1. A diagnosis of MASH documented in the participant's medical history, or a clinical suspicion of MASH based on non-invasive biomarkers and clinical risk factors, including having a history of 1 or more elements of metabolic syndrome as described in the protocol
2. Screening percutaneous liver biopsy demonstrating a NAFLD Activity Score (NAS) ≥4 and fibrosis stage F2 or F3 as described in the protocol
3. Has a FibroScan Aspartate aminotransferase (FAST) score >0.35 either at Screening Visit 1 or within approximately 3 months of Screening Visit 1 as described in the protocol

Key Exclusion Criteria:

1. Known chronic liver disease other than Metabolic dysfunction-Associated steatotic Liver Disease (MASLD), as determined by the investigator as described in the protocol
2. Prior or current suspected or known drug-induced liver injury within approximately 1 year prior to Screening Visit 1
3. History of liver transplantation, current placement on a liver transplant list, or MELD score >12
4. Known history of alcohol or other substance abuse within the last year or at any time during screening based on investigator's discretion and/or a score on the AUDIT questionnaire ≥8
5. Prior current, or planned future use of a Glucagon-Like Peptide-1 (GLP-1) receptor agonist-based therapy or any medication approved for the treatment of MASH unless used at a generally stable dose and regimen since at least 3 months prior to Screening Visit 1 or the qualifying historical liver biopsy and throughout the screening period with no change to the dose or regimen anticipated during the treatment period as described in the protocol

NOTE: Other Protocol-defined Inclusion/Exclusion Criteria Apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Administered per the protocol
Experimental: ALN-CIDEB Dose 1	Drug: ALN-CIDEB; Administered per the protocol
Experimental: ALN-CIDEB Dose 2	Drug: ALN-CIDEB; Administered per the protocol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percent change from baseline in liver fat by Magnetic Resonance Imaging-derived Proton Density Fat Fraction (MRI-PDFF)	At week 26

Secondary Outcome Measures

Outcome Measure	Time Frame
Resolution of MASH with no worsening of Nonalcoholic Steatohepatitis-Clinical Research Network (NASH-CRN) fibrosis on liver biopsy	At week 52
Percent change from baseline in liver fat by MRI-PDFF	At week 52
Achievement of a ≥30% reduction in liver fat by MRI-PDFF	At week 52
Achievement of ≤5% liver fat by MRI-PDFF	At week 52
Percent change from baseline in liver fat by MRI-PDFF for each dose level of ALN-CIDEB	Up to week 52
Improvement of NASH-CRN Fibrosis Stage (F) by ≥1 with no worsening of MASH	At week 52
Occurrence of Treatment-Emergent Adverse Events (TEAEs)	Up to week 64
Severity of TEAEs	Up to week 64
Change from baseline in FibroScan Controlled Attenuation Parameter (CAP)	Through week 52
Change from baseline in FibroScan Liver Stiffness Measurement (LSM) by Vibration Controlled Transient Elastography (VCTE)	Through week 52
Change from baseline in Aspartate Aminotransferase (AST)	Up to week 64
Change from baseline in Alanine Aminotransferase (ALT)	Up to week 64
Change from baseline in Enhanced Liver Fibrosis (ELF)	Through week 52
Change from baseline in PRO-C3	Through week 52
Change from baseline in ADAPT	Through week 52
Change from baseline in NIS2+	Through week 52
Percent change from baseline in liver fat by MRI-PDFF in genetic subpopulations	At week 52

Collaborators and Investigators

• Sponsor: Regeneron Pharmaceuticals
• Investigators: Study Director: Clinical Trial Management, Regeneron Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Estimated): July 15, 2026
• Primary Completion (Estimated): February 6, 2029
• Study Completion (Estimated): February 6, 2029

Study Registration Dates

• First Submitted: June 1, 2026
• First Submitted That Met QC Criteria: June 1, 2026
• First Posted (Actual): June 8, 2026

Study Record Updates

• Last Update Posted (Actual): June 8, 2026
• Last Update Submitted That Met QC Criteria: June 1, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Cirrhosis; Liver Fibrosis; Nonalcoholic Fatty Liver Disease (NAFLD); Metabolic dysfunction-Associated Steatotic Liver Disease (MASLD); F2 or F3 MASH; Fibrotic MASH; Liver Inflammation
• Additional Relevant MeSH Terms: Pathologic Processes; Digestive System Diseases; Liver Diseases; Fatty Liver; Pathological Conditions, Signs and Symptoms; Hepatitis; Fibrosis; Non-alcoholic Fatty Liver Disease; Liver Cirrhosis
• Other Study ID Numbers: ALN-CIDEB-MASH-2603; 2026-525916-33-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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 or has globally discontinued development of the product for all indications on or after April 2020 and has no plans for future development
• made the study results publicly available (e.g., scientific publication, scientific conference, clinical trial registry)
• the legal authority to share the data, and
• 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 Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No