Clinical trial NCT06836609: A Study to Evaluate ALN-CIDEB in Adult Participants With Metabolic Dysfunction-Associated Steatotic Liver Disease or With Metabolic Dysfunction-Associated Steatohepatitis (MASLD/MASH)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Metabolic Dysfunction-Associated Steatotic Liver Disease
Metabolic Dysfunction-Associated Steatohepatitis
Keywords: Obese
MASLD
MASH
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2025-02-20
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Part A: Sequential and Part B: Parallel
Primary purpose: TREATMENT

Brief summary: 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


Eligibility criteria: 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) ≥270 dB/m by FibroScan during screening
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 F0-F3, 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 within approximately 5 years prior to randomization or planned during the study period

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

Primary outcomes:
measure: Incidence of treatment-emergent adverse events (TEAEs)
timeFrame: Up to 48 Weeks
measure: Severity of TEAEs
timeFrame: Up to 48 Weeks
Secondary outcomes:
measure: Change in liver fat fraction by magnetic resonance imaging proton density fat fraction (MRI-PDFF)
timeFrame: Baseline up to 48 Weeks
measure: Total concentration of ALN-CIDEB in plasma
timeFrame: Up to 48 Weeks
measure: Total concentration of potential major metabolite(s) in plasma
timeFrame: Up to 48 Weeks
measure: Urinary recovery of ALN-CIDEB as a proportion of the dose
timeFrame: Up to 36 Weeks
measure: Urinary recovery of potential major metabolite(s) as a proportion of the dose
timeFrame: Up to 36 Weeks
measure: Change in aspartate aminotransferase (AST)
timeFrame: Baseline up to 48 Weeks
measure: Change in alanine aminotransferase (ALT)
timeFrame: Baseline up to 48 Weeks
measure: Change in hepatic cell death-inducing DNA fragmentation factor alpha-like effector b (CIDEB) messenger RiboNucleic Acid (mRNA) level
timeFrame: Baseline up to 36 Weeks
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Richmond Pharmacology Limited
state: Greater London
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References: