Clinical Trial Multi-analyte Blood Test (CLiMB)

Prospective Clinical Trial to Detect Liver Cancer Through Quantification of cfDNA Methylation in Blood Samples: A LAM Insight Trial Study

This is a clinical trial designed to evaluate the performance of a multi-analyte blood test alone, ultrasound alone and the combination of both the multi-analyte blood test and ultrasound for the detection of HCC within a population that is at high risk for HCC due to liver cirrhosis.

Study Overview

• Status: Active, not recruiting
• Conditions: Liver Cirrhosis
• Intervention / Treatment: Diagnostic test: Multi-analyte blood Test

Detailed Description

This multi-site, prospective study is designed to compare the sensitivity and specificity of a multi-analyte blood test alone, ultrasound alone and the combination of the multi-analyte blood test and ultrasound for the detection of HCC within a population at high risk of HCC due to liver cirrhosis. Subjects will be enrolled until the pre-determined number of subjects are enrolled.

Subjects at high risk for developing HCC due to liver cirrhosis and who are eligible for liver cancer surveillance as determined by the patient's physician and who meet all inclusion and exclusion eligibility criteria as described in this protocol, will be invited to participate in this study. Subjects will then read, understand and sign the Informed Consent Form and the HIPAA Authorization Agreement for Medical Records Form.

For each subject upon enrollment, the following blood analytes will also be determined: creatinine, prothrombin time, bilirubin, blood platelet count, ALT, AST and ALP. The results of all clinical laboratory tests will be recorded by use of the subject's Case Report Form. Whole blood samples drawn for the multi-analyte blood test will be collected (according to the instructions provided with each sample collection kit) by using the multi-analyte Sample Collection, Stabilization and Shipping Kit, and shipped to a central LAM laboratory for testing. Samples will be assayed by laboratory technicians blinded to the results of any other testing. Within the same clinical visit as the blood draws (when possible), subjects will undergo conventional ultrasound to examine the liver. Every subject will then go on to diagnostic imaging by multiphasic MRI. The results of diagnostic imaging will primarily be scored by LI-RADS score and the number and size of any malignant lesions identified will be recorded. The images of all MRI, CT, or ultrasound will be saved and uploaded for evaluation by a blinded, centralized team of radiologists to confirm diagnosis. Any biopsy results or surgical pathology results that are generated for study subjects as part of current clinical practice will also be recorded.

Study procedures will consist of conventional ultrasound to examine the liver, providing blood samples for testing with the multi-analyte blood test and other conventional blood analytes, and diagnostic imaging by multiphasic MRI.

Upon enrolling in the study, subjects will commence the Initial Surveillance Visit (t=0 months). During the Initial Surveillance Visit, all enrolled subjects will undergo ultrasound to examine the liver and provide blood samples for the multi-analyte blood test and for determining conventional blood analytes. Every subject will then go on to diagnostic imaging by multiphasic MRI. The results of diagnostic imaging will primarily be scored by a Liver Reporting and Data System (LI-RADS) score. The data of all diagnostic imaging by MRI will be saved and uploaded for evaluation by a blinded, centralized team of radiologists, which will be used as the basis of the clinical truth for all subjects.

After the Initial Surveillance Visit (t=0 months), subjects with an indeterminant HCC finding by MRI (LI-RADS 3) will be recommended to up to three Follow-Up Visits (t=6 months, t=12 months, and t=18 months) to attempt to resolve the clinical truth for these subjects. Each Follow-Up Visit will consist of an ultrasound to examine the liver, providing blood samples for the multi-analyte blood test , as well as diagnostic imaging by multiphasic MRI.

Although not required by this clinical protocol, any biopsy or surgical pathology results, or any additional imaging (such as multiphasic CT) that are generated for study subjects as part of current clinical practice will also be recorded for each subject and the results shall be made available to the Sponsor if performed within 6 months of a scheduled Visit. Biopsy and surgical pathology results that indicate a malignancy will be used in place of diagnostic imaging as the clinical truth for each subject if performed within 6 months of a scheduled visit and prior to database lock.

All study-related procedures will occur during the Study Duration Period, which consists of the Initial Surveillance Visit for all subjects and up to three Follow-Up Visits for subjects with an initial indeterminant HCC finding (LI-RADS 3) by diagnostic imaging. After this Study Duration Period, no study related blood draws, imaging or procedures will occur for these subjects.

• Study Type: Observational
• Enrollment (Estimated): 1600

Contacts and Locations

• Study Contact: Name: Arshia Akhtar; Phone Number: 6308578049 6308578049; Email: Arshia@heliohealth.com
• Study Contact Backup: Name: David Taggart, PhD; Phone Number: 6308578049 6308578049; Email: david.taggart@lamoncogroup.com

Study Locations

• United States
  • Arizona
    • Chandler, Arizona, United States, 85224
      • AZ Liver Health (Chandler)
    • Peoria, Arizona, United States, 85381
      • AZ Liver Health (Glendale, Peoria)
    • Tucson, Arizona, United States, 85712
      • AZ Liver Health (Tucson)
    • Tucson, Arizona, United States, 85724
      • Banner University Hospital (University of Arizona Tucson)
  • California
    • Irvine, California, United States, 92612
      • Alliance Research Centers
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center
    • Los Angeles, California, United States, 90033
      • University of South California
    • Palo Alto, California, United States, 94304
      • Stanford University
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Hospital - Anschutz Cancer Pavilion
  • Florida
    • Fort Myers, Florida, United States, 33012
      • Covenant Metabolic LLC
    • Gainesville, Florida, United States, 32610
      • University of Florida Clinical and Translational Science Institute
    • Miami, Florida, United States, 33136
      • University of Miami - Schiff Center for Liver Diseases
    • Naples, Florida, United States, 34102
      • Gastroenterology Group Of Naples
    • Sarasota, Florida, United States, 34240
      • Covenant Metabolics LLC
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Piedmont Research Institute
    • Atlanta, Georgia, United States, 30308
      • Atlanta Gastroenterology
  • Illinois
    • Maywood, Illinois, United States, 60153
      • Loyola University Medical Center
  • Kansas
    • Kansas City, Kansas, United States, 64111
      • St Luke's Hospital of Kansas City
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • University of Louisville
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Clinic Foundation
    • New Orleans, Louisiana, United States, 70112
      • Tulane University Health Sciences Center
    • Shreveport, Louisiana, United States, 71105
      • Louisiana Research Center, LLC
  • Missouri
    • Kansas City, Missouri, United States, 64131
      • Kansas City Research Institute (KCRI)
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27103
      • PMG Research of Winston-Salem
  • Ohio
    • Cincinnati, Ohio, United States, 45627
      • University of Cincinnati College of Medicine
  • Tennessee
    • Memphis, Tennessee, United States, 38104
      • Gastro One in Memphis
    • Nashville, Tennessee, United States, 37211
      • Quality Medical
  • Texas
    • Dallas, Texas, United States, 75234
      • Liver Center of Texas
    • Dallas, Texas, United States, 79936
      • Methodist Dallas Medical Center
    • Edinburg, Texas, United States, 78539
      • SouthTexas Research Institute
    • El Paso, Texas, United States, 79936
      • Texas Gastro Clinic
    • Houston, Texas, United States, 77065
      • Konkord Research
    • San Antonio, Texas, United States, 78215
      • Texas Liver Institute - American Research Corp.
    • Waco, Texas, United States, 76710
      • Impact Research Institute
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • Digestive & Liver Disease Specialists (DLDS) - Norfolk
    • Richmond, Virginia, United States, 23249
      • VA Richmond
  • Washington
    • Seattle, Washington, United States, 98105
      • Liver Institute Northwest
    • Seattle, Washington, United States, 98104
      • Harborview Medical Center (University of Washington)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 82 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

The maximum study duration for any given subject participating in the trial will be approximately 21 months (includes Initial Surveillance Visit and Follow-Up Visits at 6 months, 12 months and 18 months). No study-related lab assessments, imaging or procedures shall be required for any subject after the Study Duration Period.

Subject Eligibility Screening Period: 14 days Study Duration Period: Up to 21 months (includes Initial Surveillance Visit for all subjects and up to three Follow-Up Visits ONLY for subjects with indeterminant findings by diagnostic imaging) The maximum observational window for any subject enrolled in the study is expected to be approximately 21 months (for subjects with indeterminant findings by diagnostic imaging).

Description

Inclusion Criteria:

• Subject is age 21 to 84 (inclusive)
• Subject is able to read, comprehend and sign the Informed Consent Document
• Subject is willing and able to undergo liver cancer surveillance by ultrasound and the multi-analyte blood Test
• Subject is able and willing to undergo diagnostic imaging by multiphasic MRI with contrast according to the Study Protocol

• Subject has been diagnosed with liver cirrhosis by one or more of the following methods:

  1. Clinical diagnosis by blood analytes (APRI ≥ 1.5 or Bonacini cirrhosis discriminant score ≥ 8 or Lok index > 0.5)
  2. Ultrasound and Elastography > 12.5 kPa (Vibration-controlled transient elastography, Point shear wave elastography, Two-dimensional shear wave ultrasound and transient elastography or Magnetic Resonance Elastography)
  3. Diagnostic imaging by CT or MRI (liver cirrhosis indicated on radiology report)
  4. Liver biopsy (liver cirrhosis indicated on pathology report)

Exclusion Criteria:

• The study investigator deems the subject's participation to be unsafe due to an underlying medical condition
• Subject has previously been diagnosed with a primary liver cancer or a non-liver cancer that has metastasized
• Subject has previously submitted a blood sample to Helio Health (HELIO) through a separate clinical protocol
• Subject is unable or unwilling to submit blood samples for testing, undergo ultrasound or undergo diagnostic imaging by multiphasic MRI with contrast as required for the Study Protocol
• Subject has any internal metallic device or fragment, including but not limited to: A pacemaker, artificial joint or valve, surgical clips, pins, plates, screws, wire mesh or shrapnel
• It is unsafe for the subject to receive an MRI contrast dye due to pregnancy or severe kidney disease
• Subject would not routinely be recommended for HCC surveillance
• Subject received an abdominal ultrasound or diagnostic imaging by MRI or CT to image the liver within the past 5 months

Study Plan

How is the study designed?

Design Details

• Observational Models: Other
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
men or women between 21-84; Multi-analyte blood test screening alone and as combination with multi-analyte Test and Ultrasound in subjects diagnosed with liver cirrhosis	Diagnostic test: Multi-analyte blood Test; intended for the qualitative detection of DNA methylation profiles associated with hepatocellular carcinoma in cell-free DNA derived from patient whole blood specimens.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Independent performance measure of sensitivity and specificity of a multi-analyte blood test vs Ultrasound	The primary objective is to compare the performance (sensitivity and specificity) of ultrasound alone to the combination of both ultrasound and the multi-analyte blood Test for the detection of liver cancers within a high-risk population.	1 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To compare the performance (sensitivity and specificity) of ultrasound alone to the multi-analyte blood Test alone for the detection of liver cancers.	To compare the performance (sensitivity and specificity) of the multi-analyte blood Test alone to ultrasound alone for the detection of liver cancer.	1 month
To compare the performance (sensitivity and specificity) of ultrasound alone to the combination of both ultrasound and the multi-analyte blood Test for the detection of liver cancer lesions that are ≤ 2cm in diameter.	To compare the performance (sensitivity and specificity) of ultrasound alone to the combination of both ultrasound and the multi-analyte blood Test for the detection of liver cancer lesions that are ≤ 2cm in diameter.	1 month
To compare the performance (sensitivity and specificity) of ultrasound alone to the multi-analyte Test alone for the detection of liver cancer lesions that are ≤ 2cm in diameter.	To compare the performance (sensitivity and specificity) of ultrasound alone to the multi-analyte blood Test alone for the detection of liver cancer lesions that are ≤ 2cm in diameter.	1 month

Collaborators and Investigators

• Sponsor: Helio Genomics
• Investigators: Study Director: Taggart, PhD, Helio Genomics

Study record dates

Study Major Dates

• Study Start (Actual): February 4, 2019
• Primary Completion (Actual): February 1, 2023
• Study Completion (Estimated): June 30, 2024

Study Registration Dates

• First Submitted: September 28, 2018
• First Submitted That Met QC Criteria: October 1, 2018
• First Posted (Actual): October 3, 2018

Study Record Updates

• Last Update Posted (Actual): September 29, 2023
• Last Update Submitted That Met QC Criteria: September 27, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Liver Diseases; Fibrosis; Liver Cirrhosis
• Other Study ID Numbers: LAM-2018-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No