Case-Control Study of the Glycotest™ HCC Panel vs AFP for the Detection of Early-stage Hepatocellular Carcinoma

Clinical guidelines (AASLD) recommend the use of abdominal ultrasound (US) for surveillance testing for the early detection of Hepatocellular Carcinoma (HCC). The serum protein biomarker alpha-fetoprotein (AFP) is commonly used to augment US but its use alone is not recommended by clinical guidelines. Despite evidence that HCC surveillance improves early detection and reduces mortality from HCC, current HCC surveillance tests lack sensitivity, leaving a significant proportion of patients to present with late-stage disease. The Glycotest HCC Panel has shown better sensitivity than AFP, which is ineffective for the detection of early-stage HCC. This clinical study seeks to validate the Glycotest HCC Panel using a large multicenter cohort of cases and controls that includes patients diagnosed with early-stage HCC against a background of cirrhosis and cirrhotic patients without HCC (at risk) undergoing an established surveillance protocol.

Study Rationale:

This study is designed to compare the ability of the Glycotest HCC Panel with that of AFP to differentiate between patients with early-stage Hepatocellular Carcinoma (HCC) against a background of cirrhosis from cirrhotic patients without HCC (at risk).

Primary Objective:

The primary objective of this study is to determine whether the Glycotest HCC Panel outperforms AFP in terms of area under the receiver operating characteristic curve (AUROC) for the differentiation of patients with early-stage HCC from those without HCC in the at-risk population.

Secondary Objective:

The secondary objective of this study is to determine whether the Glycotest HCC Panel outperforms AFP in terms of clinical sensitivity (as estimated using the 90% specificity estimate as the decision threshold) for the detection of patients with early-stage HCC.

Study Design:

This is a phase 2, multicenter, laboratory-blinded, case-control study of the Glycotest HCC Panel vs AFP for the discrimination of patients with early-stage HCC from those at risk. Case and control samples will be obtained from multiple institutions using prospective collection. The study will consist of a screening/baseline visit for all patients; controls initially assessed by abdominal US will also undergo a 6-month follow-up visit to confirm absence of HCC at enrollment. Assays will be performed by Glycotest with analysts blinded to clinical data.

Population:

The study population will comprise male and female adult patients with early-stage HCC against a background of cirrhosis (cases) as well as at-risk cirrhotic patients (controls). Enrollment of the aggregate of HCC cases with single lesions ≥ 3 cm and with multiple lesions will be capped at 50% of total cases. Enrollment of Chronic Hepatitis C cases and controls with sustained virologic response (SVR) to therapy will be matched. Cases and controls will be matched based on age, sex and etiology.

Number of Subjects:

Maximum of 388 cases and 378 controls;

• 150 cases and 140 controls (training set)
• Maximum of 238 cases and 238 controls (validation set)

Study Duration:

30 months ( approximately 24 months accrual + 6 month follow up)

Study Phases Patients potentially eligible for the study population will undergo informed consent prior to screening/baseline visits.

Screening Once consented, a subject's demographics, medical record, laboratory data, and imaging will be reviewed. Patients are considered eligible for enrollment once they meet all study enrollment criteria.

Enrollment Screening data will be re-reviewed if necessary and recorded. Serum from blood samples (5 mL) will be obtained for measurement of Glycotest HCC Panel score (which includes AFP).

Follow up Medical record review/imaging at 6 months from enrollment for control patients originally assessed using abdominal US.