Safety and Efficacy of Atorvastatin v. Placebo on HCC Risk

NCT05028829 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 21-444
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 2

Brief Summary

Prospective randomized, multi-center, double blind placebo-controlled trial to assess the chemopreventive impact of atorvastatin (20 mg oral) vs placebo in up to 60 adults with advanced fibrosis at high risk of developing HCC.

Conditions

Liver Fibroses; Cirrhosis

Keywords

Liver Disease; Chemoprevention; HCC; Atorvastatin

Outcome Measures

Primary Outcomes (1)

• Reduced magnitude of high-risk PLSec after treatment vs before treatment

  The primary objective (primary endpoint) of this study is to determine the effect of atorvastatin compared with placebo on HCC risk level measured by change in serum-based prognostic liver secretome signature (PLSec) score (delta-PLSec). High-risk for HCC is indicated by a PLSec score of 3 or greater. Low-risk for HCC is indicated by a PLSec score below 3.

  48 weeks

Secondary Outcomes (2)

• Complete adverse event profile

  48 weeks

• Complete profile of change in quality of life for patients

  48 weeks

Other Outcomes (6)

• Exploratory Endpoint: Modulation of high-risk Prognostic Liver Signature (PLS) after treatment vs before treatment

  48 weeks

• Exploratory Endpoint: Assessment of Pharmacokinetic (PK) Biomarkers of Atorvastatin

  48 weeks

• Exploratory Endpoint: Assessment of Pharmacodynamic (PD) Biomarkers of Atorvastatin

  48 weeks

Study Arms (2)

Group A: Atorvastatin 20 mg

EXPERIMENTAL

Atorvastatin 20mg will be administered daily via oral route for 48 consecutive weeks on an outpatient basis.

Drug: Atorvastatin 20mg

Group B: Placebo to Match (PTM)

PLACEBO COMPARATOR

PTM will be administered daily via oral route for 48 consecutive weeks on an outpatient basis.

Drug: Placebo

Interventions

Atorvastatin 20mg DRUG

Oral administration of atorvastatin 20 mg

Also known as: Lipitor

Group A: Atorvastatin 20 mg

Placebo DRUG

Oral administration of placebo

Group B: Placebo to Match (PTM)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Willing and able to provide informed consent
• Male or female age \> 18 years at time of consent
• Clinically or histologically diagnosed advanced liver fibrosis or cirrhosis, as defined by one or more of the following:
• Liver biopsy demonstrating advanced fibrosis or cirrhosis (METAVIR 3-4)
• Fibroscan or MR elastography consistent with advanced fibrosis or cirrhosis
• Imaging showing cirrhotic-appearing liver with signs of portal hypertension
• Advanced fibrosis or cirrhosis documented clinically by a treating physician
• High-risk for HCC at screening according to the FIB-4 index
• PLSec score ≥ 3 measured in screening blood samples from the FIB-4-high individuals.
• Liver imaging within 6 months of Day 1 is required in cirrhotic subjects only, to exclude HCC
• Female subjects of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception
• Willing and able to undergo protocol blood sampling
• Subject must be able to comply with dosing instructions for study drug administration and able to complete study schedule of assessments

You may not qualify if:

• Diagnosis of any of the following forms of chronic liver disease:
• alpha-1-antitrypsin (A1AT) deficiency, Wilson disease, hemochromatosis, iron overload, prior known or suspected drug-induced liver injury (DILI)
• Patients with PBC, PSC, AIH, or stable hemochromatosis may be included if their liver disease etiology overlaps with that of steatotic liver disease (SLD)
• Current or prior history of any of the following:
• \- Clinically significant illness or any other major medical disorder that in the opinion of the investigator, may interfere with subject treatment, assessment or compliance with the protocol
• Known positivity for HIV infection
• Active, untreated HCV infection
• \- Patients with prior history of HCV who achieved sustained virologic response (SVR) \>12 from Day 1 may be included in the study
• Uncontrolled chronic HBV
• \- Patients with well controlled disease with \>12 months of stable medication use (or no medication use, in those persons for whom anti-HBV therapy is not indicated)
• Clinical hepatic decompensation, defined as Child's Pugh class \>B7 or C cirrhosis
• \- Patients with Child's Pugh score of 7, class B, may be included in the study
• History of biliary diversion
• Solid organ transplant
• Malignancy within the 5 years prior to screening, with the exception of specific cancers that have been cured by surgical resection (basal cell skin cancer, etc). Subjects under evaluation for possible malignancy are not eligible

Sponsors & Collaborators

• Raymond Chung: lead
• University of Texas Southwestern Medical Center: collaborator

Study Sites (2)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

RECRUITING

MeSH Terms

Conditions

Liver Cirrhosis; Fibrosis; Liver Diseases

Interventions

Atorvastatin

Condition Hierarchy (Ancestors)

Digestive System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids

Study Officials

• Raymond Chung, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Raymond Chung, MD

CONTACT

617-724-7526; chung.raymond@mgh.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director of Hepatology, MGH

Study Record Dates

• First Submitted: August 25, 2021
• First Posted: August 31, 2021
• Study Start: May 10, 2023
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): March 1, 2031
• Last Updated: September 23, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: 1/2025-1/2026
• Access Criteria: Researchers accessing IPD must be approved and have a data use agreement in place with Mass General Brigham to access the data.

Locations

US (2)