Safety and Efficacy of Atorvastatin v. Placebo on HCC Risk

Launched by RAYMOND CHUNG · Aug 25, 2021

Keywords

ClinConnect Summary

This clinical trial is studying the effects of a medication called atorvastatin on reducing the risk of developing liver cancer (HCC) in adults who have advanced liver damage, known as fibrosis or cirrhosis. The trial involves giving some participants atorvastatin and others a placebo (a harmless pill with no active ingredients) to see if atorvastatin can help prevent liver cancer in people who are at high risk. The study is currently recruiting participants aged 18 and older who meet specific health criteria, including a diagnosis of advanced liver fibrosis or cirrhosis.

Participants in this trial can expect to take the medication or placebo for a certain period and will need to undergo regular check-ups to monitor their health. To be eligible, individuals must be willing to give consent, have advanced liver conditions, and be at high risk for liver cancer according to specific medical tests. It's important to note that there are some health conditions that would exclude someone from participating, including certain chronic liver diseases and recent serious health issues. Overall, this study aims to find out if atorvastatin can be a useful tool in preventing liver cancer in those who need it most.

Gender

ALL

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