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

Regeneron Pharmaceuticals

Status and phase: Not yet enrolling; Phase 1

Conditions: Metabolic Dysfunction-Associated Steatotic Liver Disease; Metabolic Dysfunction-Associated Steatohepatitis

Treatments: Drug: ALN-CIDEB; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT06836609

ALN-CIDEB-NASH-2486

Details and patient eligibility

About

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

Enrollment: 100 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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 imagining 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Double Blind

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100 participants in 2 patient groups

Part A

Experimental group

Description:

Randomized per the protocol

Treatment:

Drug: Placebo

Drug: ALN-CIDEB

Part B

Experimental group

Description:

Randomized per the protocol

Treatment:

Drug: Placebo

Drug: ALN-CIDEB