RECRUITING

Safety and Efficacy of Atorvastatin v. Placebo on HCC Risk

Conditions

Liver Fibroses Cirrhosis Liver Disease Chemoprevention HCC Atorvastatin

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

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

Quick Facts

Study Start:2023-05-10

Study Completion:2031-03-01

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05028829

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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	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: 3. Known positivity for HIV infection 4. Active, untreated HCV infection 5. Uncontrolled chronic HBV 6. Clinical hepatic decompensation, defined as Child's Pugh class \>B7 or C cirrhosis 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 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

Inclusion Criteria

Exclusion 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

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:
3. Known positivity for HIV infection
4. Active, untreated HCV infection
5. Uncontrolled chronic HBV
6. Clinical hepatic decompensation, defined as Child's Pugh class \>B7 or C cirrhosis
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
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

Contacts and Locations

Study Contact

Raymond Chung, MD

CONTACT

617-724-7526

chung.raymond@mgh.harvard.edu

Principal Investigator

Raymond Chung, MD

PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital

Study Locations (Sites)

Massachusetts General Hospital

Boston, Massachusetts, 02114

United States

University of Texas Southwestern Medical Center

Dallas, Texas, 75390

United States

Collaborators and Investigators

Sponsor: Raymond Chung

Raymond Chung, MD, PRINCIPAL_INVESTIGATOR, Massachusetts General Hospital

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-05-10

Study Completion Date2031-03-01

Study Record Updates

Study Start Date2023-05-10

Study Completion Date2031-03-01

Terms related to this study

Keywords Provided by Researchers

Liver Disease
Chemoprevention
HCC
Atorvastatin

Additional Relevant MeSH Terms

Liver Fibroses
Cirrhosis