Evaluating atorvastatin's effect on liver cancer risk in patients with advanced fibrosis

Multi-center Double Blind, Placebo-controlled Study to Evaluate the Safety and Efficacy of Long-term Atorvastatin (20 mg/Day) v. Placebo on HCC Risk in Individuals With Advanced Liver Fibrosis

This study is testing if taking atorvastatin can lower the risk of liver cancer in adults with advanced liver fibrosis who are at high risk for developing the disease.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Massachusetts General Hospital (Academic / other)
• Locations: 2 sites (Boston, Massachusetts and 1 other locations)
• Trial ID: NCT05028829 on ClinicalTrials.gov

What this trial studies

This clinical trial is a prospective randomized, multi-center, double-blind placebo-controlled study aimed at assessing the chemopreventive impact of atorvastatin (20 mg orally) compared to a placebo in adults with advanced liver fibrosis at high risk for developing hepatocellular carcinoma (HCC). The study will enroll up to 60 participants and will measure changes in the prognostic liver secretome signature (PLSec) risk score after one year of atorvastatin treatment, followed by up to five years of monitoring. Participants must have a confirmed diagnosis of advanced fibrosis or cirrhosis and a high-risk PLSec score as determined by pre-randomization blood tests.

Who should consider this trial

Good fit: Ideal candidates for this study are adults over 18 years old with clinically or histologically diagnosed advanced liver fibrosis or cirrhosis and a high risk of HCC.

Not a fit: Patients without advanced liver fibrosis or cirrhosis, or those not at high risk for HCC, may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a new preventive treatment option for patients at high risk of developing liver cancer.

How similar studies have performed: Other studies have explored the use of atorvastatin for liver-related conditions, but this specific approach to chemoprevention in high-risk patients is novel.

Eligibility criteria

Inclusion Criteria:

1. Willing and able to provide informed consent
2. Male or female age \> 18 years at time of consent
3. 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
4. High-risk for HCC at screening according to the FIB-4 index
5. PLSec score ≥ 3 measured in screening blood samples from the FIB-4-high individuals.
6. Liver imaging within 6 months of Day 1 is required in cirrhotic subjects only, to exclude HCC
7. Female subjects of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception
8. Willing and able to undergo protocol blood sampling
9. Subject must be able to comply with dosing instructions for study drug administration and able to complete study schedule of assessments

Exclusion Criteria:

1. 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)
2. 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
3. Known positivity for HIV infection
4. 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
5. 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)
6. 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
7. History of biliary diversion
8. Solid organ transplant
9. 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
10. Pregnant or Nursing Females (a negative serum pregnancy test is required at screening for WOCBP)
11. Life threatening SAE during the screening period
12. Subjects having the following laboratory parameters at screening

    * ALT \> 10 x ULN
    * AST \> 10 x ULN
    * Hemoglobin \< 8.5 g/dl
    * Serum creatinine \> 2.0 mg/dL
    * CK \> 3x ULN
13. Females who may wish to become pregnant and/or plan to undergo egg harvesting during the study and up to 30 days of the last dose of study drug
14. WOCBP must abstain from breastfeeding and be willing to use effective birth control during through the week 4 post treatment follow-up visit
15. Clinically relevant alcohol or drug abuse within 12 months of screening
16. Use of any prohibited concomitant medications as described in Section 9.1.1
17. Use of a statin medication within 90 days of Day 1 visit

    \- Subjects who are on a current statin at time of consent must be willing to undergo a 90-day washout period prior to randomization
18. Known hypersensitivity to atorvastatin
19. Current or planned participation in an investigational new drug (IND) trial from 30-days prior to randomization through the week 4 post treatment follow-up visit

Where this trial is running

Boston, Massachusetts and 1 other locations

• Massachusetts General Hospital — Boston, Massachusetts, United States (Recruiting)
• University of Texas Southwestern Medical Center — Dallas, Texas, United States (Recruiting)

Study contacts

• Principal investigator: Raymond Chung, MD — Massachusetts General Hospital
• Study coordinator: Raymond Chung, MD

Conditions Liver Fibroses; Cirrhosis; Liver Disease; Chemoprevention; HCC; Atorvastatin