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Safety and Efficacy of Atorvastatin v. Placebo on HCC Risk

ConditionsLiver FibrosesCirrhosis
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorRaymond Chung

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Willing and able to provide informed consent

Male or female age > 18 years at time of consent

Liver biopsy demonstrating advanced fibrosis or cirrhosis (METAVIR 3-4)

Fibroscan or MR elastography consistent with advanced fibrosis or cirrhosis

Disqualifiers

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)

Known positivity for HIV infection

Active, untreated HCV infection

Trial design

Design model

Parallel

Treatments tested in this trial

  • Atorvastatin 20mg

    Drug

    Oral administration of atorvastatin 20 mg

  • Placebo

    Drug

    Oral administration of placebo

Treatment groups

60 Participants
are divided into 2 treatment groups
Group A: Group A: Atorvastatin 20 mgExperimental treatment 1 intervention
Group B: Group B: Placebo to Match (PTM)Placebo comparator 1 intervention

Trial outcomes

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.

Time frame
48 weeks

Secondary outcomes

1

Complete adverse event profile

Minimized toxicity in response to treatment based on NCI Common Terminology Criteria for Adverse Events (CTCAE) v.5 at least every 4 weeks to week 12 and at weeks 24, 36, and 48.

Time frame
48 weeks
2

Complete profile of change in quality of life for patients

The investigators will assess the subjects' quality of life while on treatment using the Chronic Liver Disease Questionnaire (CLDQ). A Likert scale response format will be used for all items (n=29), and the overall CLDQ score will be obtained by adding scores for each item and dividing by the total number of items (n=29). The score ranges from 1 (most impairment) to 7 (least impairment).

Time frame
48 weeks

Other outcomes

1

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

The investigators will assess the significant magnitude of modulation in PLS-based HCC risk level calculated as the Combined Enrichment Score (CES) jointly measuring suppression of high-risk-associated genes and induction of low-risk-associated genes in the PLS. A negative CES indicates reduction of HCC risk level. The Mean CES between the treatment arms will be compared by using a two-sample t-test.

Time frame
48 weeks
2

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

The investigators will assess the PK biomarkers of atorvastatin in serum from baseline and week 48. Serum atorvastatin concentration (ng/mL) will be measured between the atorvastatin group and placebo group.

Time frame
48 weeks
3

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

The investigators will assess the PD biomarkers of atorvastatin in serum from baseline and week 48. Serum Low-Density Lipoprotein, or LDL (mg/mL) and total cholesterol concentration (mg/mL) will be measured between the atorvastatin group and placebo group.

Time frame
48 weeks
4

Exploratory Endpoint: Assess the difference in HCC incidence rate between treatment groups

After subjects complete their on-treatment period, the study team will conduct a 5-year post-treatment observational study to examine the incidence rate of HCC between the atorvastatin group and the placebo group.

Time frame
288 weeks

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Raymond Chung

Lead sponsor

Massachusetts General Hospital

Sponsor institution

University of Texas Southwestern Medical Center

Collaborator

Source ClinicalTrials.gov
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