A Study to Evaluate ALN-CIDEB in Adult Participants With Metabolic Dysfunction-Associated Steatotic Liver Disease or With Metabolic Dysfunction-Associated Steatohepatitis (MASLD/MASH)

A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Two-Part Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of a Single Dose of ALN-CIDEB in Adult Participants With Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) and Two Doses of ALN-CIDEB in Adult Participants With Metabolic Dysfunction-Associated Steatohepatitis (MASH)

This study is researching an experimental drug called ALN-CIDEB, also referred to as "study drug". The study is focused on participants with metabolic dysfunction-associated steatotic liver disease (MASLD) (Part A) and metabolic dysfunction-associated steatohepatitis (MASH) (Part B). MASLD and MASH are long-lasting liver conditions caused by having too much fat in the liver.

The aim of the study is to see how safe and tolerable the study drug is.

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

• What side effects may happen from taking the study drug
• How the study drug works to change liver fat content
• How much study drug and study drug metabolites (byproducts of the body breaking down the study drug) are in the blood at different times

Study Overview

• Status: Recruiting
• Conditions: Metabolic Dysfunction-Associated Steatohepatitis; Metabolic Dysfunction-Associated Steatotic Liver Disease
• Intervention / Treatment: Drug: Placebo; Drug: ALN-CIDEB

• Study Type: Interventional
• Enrollment (Estimated): 132
• Phase: Phase 2; Phase 1

Contacts and Locations

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

Study Locations

• United Kingdom
  • Greater London
    • London, Greater London, United Kingdom, SE1 1YR
      • Recruiting
      • Richmond Pharmacology Limited
  • London
    • Harrow, London, United Kingdom, HA1 3UJ
      • Recruiting
      • Parexel International Early Phase Clinical Unit
• United States
  • Arizona
    • Chandler, Arizona, United States, 85225
      • Recruiting
      • Arizona Liver Health

Participation Criteria

Eligibility Criteria

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

Description

Key Inclusion Criteria:

1. Part A: 18 to 55 years at Screening Visit 1 with MASLD, at Screening Visit 1 Part B: 18 to 65 years at Screening Visit 1 with a diagnosis of MASH, at Screening Visit 1
2. Body Mass Index (BMI) ≥30 kg/m2 and ≤40 kg/m2 at Screening Visit 1
3. Controlled-Attenuation Parameter (CAP) ≥285 dB/m by FibroScan during screening as described in the protocol
4. Liver fat content ≥8.5% by MRI-PDFF during screening
5. If on anti-hypertensive and/or lipid lowering medications and/or glucose lowering medications, must be on generally stable dose(s) for at least 12 weeks prior to screening and no changes to the dose(s) are anticipated during the study
6. Part B: A diagnosis of MASH documented in the participant's medical history, or a clinical suspicion of MASH based on non-invasive biomarkers (eg, evidence of fatty liver on imaging and elevated liver enzymes) and clinical risk factors, including having a history of 2 or more elements of metabolic syndrome, as defined in the protocol
7. Part B: Screening percutaneous liver biopsy NAFLD Activity Score (NAS) ≥3 and fibrosis stage, as defined in the protocol

Key Exclusion Criteria:

1. Known historical or current diagnosis of portal hypertension or cirrhosis based on clinical assessment, imaging, and/or liver biopsy
2. Known historical or current diagnosis of other forms of chronic liver disease, as defined in the protocol
3. Prior or current suspected or known drug-induced liver injury within 1 year prior to screening
4. History of liver transplant, current placement on a liver transplant list, or Model for End-stage Liver Disease (MELD) score >12
5. Contraindication to MRI examinations, such as persons with cardiac pacemaker and implants made of metal, severe claustrophobia, size restrictions, or other contraindications for MRI
6. Liver stiffness measurement, laboratory parameter assessment, estimated Glomerular Filtration Rate (GFR), and evidence of uncontrolled hypertension, as defined in the protocol
7. Evidence of Human Immunodeficiency Virus (HIV) infection, Hepatitis B Virus (HBV) infection, or Hepatitis C Virus (HCV) infection during screening, as described in the protocol
8. History of Type 1 Diabetes
9. Bariatric surgery, including any procedures to revise, reverse, or remove any previous bariatric surgery interventions, within approximately 5 years prior to randomization or planned during the study period

NOTE: Other protocol-defined inclusion/exclusion criteria apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A; Randomized per the protocol	Drug: Placebo; Administered per the protocol; Drug: ALN-CIDEB; Administered per the protocol
Experimental: Part B; Randomized per the protocol	Drug: Placebo; Administered per the protocol; Drug: ALN-CIDEB; Administered per the protocol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Severity of TEAEs	Up to 48 Weeks
Incidence of Treatment-Emergent Adverse Events (TEAEs)	Up to 48 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total concentration of ALN-CIDEB in plasma		Up to 48 Weeks
Total concentration of potential major metabolite(s) in plasma		Up to 48 Weeks
Urinary recovery of ALN-CIDEB as a proportion of the dose	Part A	Up to 36 Weeks
Urinary recovery of potential major metabolite(s) as a proportion of the dose	Part A	Up to 36 Weeks
Change in liver fat fraction by Magnetic Resonance Imaging-Proton Density Fat Fraction (MRI-PDFF)		Baseline up to 48 Weeks
Change in Aspartate Aminotransferase (AST)		Baseline up to 48 Weeks
Change in Alanine Aminotransferase (ALT)		Baseline up to 48 Weeks
Change in hepatic Cell death-Inducing DNA fragmentation factor alpha-like Effector B (CIDEB) messenger RiboNucleic Acid (mRNA) level	Part B	Baseline up to 36 Weeks

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): April 28, 2025
• Primary Completion (Estimated): May 15, 2027
• Study Completion (Estimated): May 15, 2027

Study Registration Dates

• First Submitted: February 14, 2025
• First Submitted That Met QC Criteria: February 14, 2025
• First Posted (Actual): February 20, 2025

Study Record Updates

• Last Update Posted (Actual): April 27, 2026
• Last Update Submitted That Met QC Criteria: April 22, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Obese; MASLD; MASH
• Additional Relevant MeSH Terms: Nutrition Disorders; Overnutrition; Body Weight; Overweight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Obesity; Substandard Drugs; Pharmaceutical Preparations; Counterfeit Drugs
• Other Study ID Numbers: ALN-CIDEB-NASH-2486

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