Efficacy of EsoGuard Assay on Esophageal Surface Cells Collected With EsoCheck vs EGD for the Diagnosis of BE or EAC (ESOGUARDBE2)

• ClinicalTrials.gov Identifier: NCT04295811
• Recruitment Status: Recruiting
• First Posted: March 5, 2020
• Last Update Posted: October 5, 2020
• Sponsor: Lucid Diagnostics, Inc.
• Information provided by (Responsible Party): PAVmed Inc. ( Lucid Diagnostics, Inc. )

Study Description

Brief Summary:

The study will assess the performance of the combined system, i.e., the use of the EsoGuard assay (lab developed test) on cells collected using the EsoCheck (501k cleared device) to detect Barrett's Esophagus (BE), with or without dysplasia, and esophageal adenocarcinoma (EAC) as compared to Esophagogastroduodenoscopy (EGD) plus biopsies in both confirmed cases of BE/EAC and in controls (subjects without a prior diagnosis but undergoing screening for BE/EAC)

Condition or disease	Intervention/treatment	Phase
Barrett Esophagus; Esophageal Adenocarcinoma; Barretts Esophagus With Dysplasia; Barrett's Esophagus Without Dysplasia	Device: EsoGuard (lab assay); Diagnostic Test: Esophagogastroduodenoscopy	Not Applicable

Detailed Description:

This is a two phase multicenter study to assess the operating characteristics of the EsoGuard diagnostic assay panel performed on esophageal mucosal cells collected using the EsoCheck cell collection device in known "Cases" of disease (i.e., patients with a history of Barrett's Esophagus (BE) with and without varying degrees of dysplasia or intramucosal adenocarcinoma [IMC]) and in patients with no known history of these conditions. The latter are presumed to be "Controls", though this final determination is made as part of study conduct, not at the time of enrollment.

The study is divided into a Run-In phase and an Efficacy phase. The assignment of a patient to one or the other of these two phases will be made based on two pieces of information: 1) the Final Study Diagnosis (as defined below) and 2) the current tally versus the pre-determined target number of patients already assigned to each of the subgroups (e.g., non-dysplastic Barrett's Esophagus (NDBE), high grade dysplasia {HGD]) for each phase. Patients will first be enrolled into the Run-In phase subgroups. Only once the targeted enrollment for a given Run-In phase subgroup has been reached, subsequent patients with a particular diagnosis will be assigned to the appropriate Efficacy Phase subgroup, until the targeted total number is reached. Run In phase data will be maintained in a separate database from Efficacy phase data. Study conduct is identical in both phases; however, data from each phase will be segregated and analysis of each phase will be used solely for its predetermined purpose without any co-mingling of data. Once assigned, no patient, or their data, will be re-assigned or moved from being a Run-In phase patient to being an Efficacy phase patient, or from the Run-In phase database to the Efficacy phase database, or vice versa.

The Run-In phase will enroll the initial 60 short segment NDBE (also known as short segment Barrett's Esophagus [SSBE]) and 25 long segment NDBE (also known as long segment Barrett's Esophagus [LSBE]) Cases, the initial 10 low grade dysplasia [LGD] Cases, the initial 3 high grade dysplasia [HGD] Cases, and the initial 2 intramucosal adenocarcinoma [IMC] Cases, as well as the initial 100 Controls. The Efficacy phase will enroll 54 Cases each with a Final Study Diagnosis of NDBE, LGD, HGD, and IMC, and 54 Controls.

Run-In phase data will be used solely to derive the optimal numerical cutoffs by which to score mVIM and mCCNA1 (which are two genes where the methylated DNA changes are located) positivity or negativity. These cutoffs serve as the key inputs into an algorithm by which an overall EsoGuard result of positive versus negative is determined. The setting of these cutoffs will be done by Sponsor personnel with full access to all Run-In phase data; the goal will be to optimize overall EsoGuard assay sensitivity and specificity for its intended use as a screening test in the at-risk population. The assay, once validated and locked, will be used to analyze patients' distal esophageal cells obtained in both the Efficacy phase of this Case Control study as well as in a separate Screening study (PR-1039/EG-CL-101) to be conducted in parallel. Only Run-In phase data will be used to set cutoffs. The mVIM and mCCNA1 (i.e., genes with methylated DNA changes) cutoffs will be set and then the EsoGuard assay re validated and "locked", all before any Efficacy phase distal esophageal cells specimens collected from study patients will undergo EsoGuard analysis.

Sponsor personnel will have open access to all Run-In phase data during the enrollment of the Run-In phase in order to determine if the data from patients enrolled to date is sufficient to inform adequately the setting of cutoffs. If Sponsor so determines, it may elect to terminate enrollment in the Run-In phase early (i.e., prior to enrolling the 100 Cases and 100 Controls listed above). If early termination of the Run-In phase is elected, all patients enrolled subsequent to the date Sponsor makes this election will be entered into the Efficacy phase and such subsequent patients will count towards the Efficacy phase enrollment objectives.

As well, should Sponsor complete the intended Run-In phase enrollment of 100 Cases and 100 Controls but determine, upon its assessment of the resulting data, that data from additional Cases could improve the setting of cutoffs, Sponsor may decide to enroll up to 100 additional Run-In phase Cases. These 100 Cases may be in whatever distribution of disease Sponsor elects (i.e., ranging from NDBE through to IMC). In order to augment the Run-In phase patient counts, the Sponsor will set updated targets for enrollment of each Run-In phase subgroup and will assign patients to each Run-In subgroup to be augmented, based on patients' Final Study Diagnosis and on whether the updated subgroup target has been met. When each updated subgroup enrollment target has once again been met, subsequent patients with that subgroup diagnosis will be enrolled into the Efficacy phase.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 470 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: Multi-center, single arm
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: A Multicenter Case-Control Study of the Efficacy of EsoGuard on Samples Collected Using EsoCheck, Versus Esophagogastroduodenoscopy, for the Diagnosis of Barrett's Esophagus With and Without Dysplasia, and for Esophageal Adenocarcinoma
• Actual Study Start Date: June 18, 2020
• Estimated Primary Completion Date: December 2022
• Estimated Study Completion Date: December 2022

Arms and Interventions

Arm

Intervention/treatment

Experimental: EsoCheck and EsoGuard vs. EGD with or without biopsies; All subjects will undergo both the EsoGuard lab assay run on distal esophageal cells collected with EsoCheck (non-invasive esophageal cell sample collection) device followed by Esophagogastroduodenoscopy (EGD) with or without biopsies

Device: EsoGuard (lab assay); EsoGuard assay (LDT) will be used on cells collected using the EsoCheck (510K cleared esophageal cell collection device); Other Name: EsoCheck (esophageal cell sample collection device); Diagnostic Test: Esophagogastroduodenoscopy; Planned EGD to diagnose and/or treat disorders of esophagus, stomach, and small intestine. When abnormal tissues are noted, biopsies of the tissue are taken through the scope to diagnose tissue abnormalities.; Other Name: EGD

Outcome Measures

Primary Outcome Measures :

1. Primary Efficacy [ Time Frame: Per subject analysis through study completion which is up to approximately 5 weeks ]
   The primary efficacy endpoint is the sensitivity of EsoGuard. The primary efficacy objectives of this study are to measure the sensitivities of EsoGuard-based diagnosis in 54 cases each of non-dysplastic Barrett's Esophagus (NDBE), low grade dysplasia (LGD), high grade dysplasia (HGD), and intramucosal adenocarcinoma (IMC) in order to assess EsoGuard's ability to detect disease across the entire continuum of disease progression.

Secondary Outcome Measures :

1. Secondary Efficacy [ Time Frame: Per subject through study completion which is up to approximately 5 weeks ]
   The secondary efficacy outcome will be the specificity of EsoGuard (which are run on samples collected using EsoCheck) for Controls. Specificity of EsoGuard will be calculated for the controls as the number of controls who test negative via EsoGuard divided by the total number of controls.

Other Outcome Measures:

1. Safety outcome of EsoCheck Device (510k cleared, non-invasive, esophageal cell collection device) on all patients who undergo the device procedure. [ Time Frame: Per subject through study completion which is up to approximately 5 weeks ]
   Assessed by evaluation of esophageal abrasions (as visualized during esophagogastroduodenoscopy[EGD]) when EsoCheck and EGD procedures are performed the same day as well as adverse events (AEs) serious adverse events (SAEs), adverse device effects (ADEs), serious adverse devices effects (SADEs), unanticipated serious adverse device effects (USADEs) and Medical Device Deficiency Incidents.

Eligibility Criteria

• Ages Eligible for Study: 22 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

All Patients:

1. Men aged 50 years and above

2. ≥5 years either of

   • Gastroesophageal Reflux Disease (GERD) symptoms,
   • GERD treated with proton pump inhibitor (PPI) therapy (whether symptom control is achieved or not), or
   • any combination of treated and untreated periods, as long the cumulative total is at least 5 years
3. No solid foods eaten for at least 2 hours prior to EsoCheck procedure

4. One or more of the following:

   • Caucasian race
   • Current or past history of chronic smoking
   • Body mass index (BMI) of at least 30 kg/m2
   • First-degree relative with Barrett's Esophagus (BE) or Esophageal Adenocarcinoma (EAC)

Cases:

1. Previous diagnosis of non-dysplastic Barrett's Esophagus (NDBE), low grade dysplasia (LGD), high grade dysplasia (HGD), and/or intramucosal adenocarcinoma (IMC)
2. Diagnosis by esophagogastroduodenoscopy (EGD) (with exception of NDBE) was within 4 months prior to study enrollment
3. Indicated for surveillance EGD or for therapeutic EGD
4. Able to provide, by day of study EGD, the original glass slide(s) of biopsy specimens from most recent prior EGD

Exclusion Criteria:

1. Inability to provide written informed consent
2. On anti-coagulant drug(s) that cannot be temporarily discontinued
3. Known history of esophageal varices or esophageal stricture
4. Any contraindication, as deemed in Investigator's medical judgment, to undergoing the EsoCheck procedure, undergoing the EGD procedure, and/or having biopsies taken, including but not limited to due to comorbidities such as coagulopathy or a known history of esophageal diverticula, esophageal fistula, and/or esophageal ulceration
5. History of difficulty swallowing (dysphagia) or painful swallowing (odynophagia), including swallowing pills
6. Oropharyngeal tumor
7. History of esophageal or gastric surgery, with exception of uncomplicated surgical fundoplication procedure
8. History of myocardial infarction or cerebrovascular accident within past 6 months
9. Any known lesion which, in the opinion of the endoscopist, obstructs greater than 25% of the esophageal lumen
10. Prior participation in PR-0139/EG-CL-101 (Lucid BE Screening Study)
11. Prior EGD during which a therapeutic procedure such as, but not limited to, ablation, cryotherapy or endoscopic mucosal resection, was performed for the treatment of BE and/or EAC

Contacts and Locations

Contacts

Contact: Randy Brown, MS; 212-949-4319; RWB@LucidDx.com

Contact: Lisa Gott, RN, BA; LLG@lucidDX.com

Locations

United States, Alabama

Lucid Investigative Site; Not yet recruiting

Birmingham, Alabama, United States, 35294

United States, California

Lucid Investigative Site; Not yet recruiting

Orange, California, United States, 92868

United States, Colorado

Lucid Investigative Site; Not yet recruiting

Aurora, Colorado, United States, 80045

Lucid Investigative Site; Not yet recruiting

Englewood, Colorado, United States, 80113

United States, District of Columbia

Lucid Investigative Site; Not yet recruiting

Washington, District of Columbia, United States, 20007

United States, Florida

Lucid Investigative Site; Recruiting

Jacksonville, Florida, United States, 32256

United States, Illinois

Lucid Investigative Site; Not yet recruiting

Chicago, Illinois, United States, 60611

United States, Maryland

Lucid Investigative Site; Not yet recruiting

Baltimore, Maryland, United States, 21287

United States, Massachusetts

Lucid Investigative Site; Not yet recruiting

Boston, Massachusetts, United States, 02215

United States, Michigan

Lucid Investigative Site; Not yet recruiting

Ann Arbor, Michigan, United States, 48109

United States, Missouri

Lucid Investigative Site; Not yet recruiting

Saint Louis, Missouri, United States, 63110

United States, New Hampshire

Lucid Investigative Site; Not yet recruiting

Lebanon, New Hampshire, United States, 03756

United States, New York

Lucid Investigative Site; Recruiting

New Hyde Park, New York, United States, 11030

Lucid Investigative Site; Not yet recruiting

Rochester, New York, United States, 14620

United States, North Carolina

Lucid Investigative Site; Recruiting

Chapel Hill, North Carolina, United States, 27599

United States, Oregon

Lucid Investigative Site; Not yet recruiting

Portland, Oregon, United States, 97239

United States, Pennsylvania

Lucid Investigative Site; Not yet recruiting

Philadelphia, Pennsylvania, United States, 19104

Lucid Investigative Site; Not yet recruiting

Philadelphia, Pennsylvania, United States, 19107

United States, Rhode Island

Lucid Investigative Site; Not yet recruiting

Providence, Rhode Island, United States, 02903

United States, South Carolina

Lucid Investigative Site; Not yet recruiting

Charleston, South Carolina, United States, 29425

Lucid Investigative Site; Not yet recruiting

Greenville, South Carolina, United States, 29615

United States, Tennessee

Lucid Investigative Site; Recruiting

Knoxville, Tennessee, United States, 37909

Lucid Investigative Site; Recruiting

Nashville, Tennessee, United States, 37212

United States, Texas

Lucid Investigative Site; Not yet recruiting

Austin, Texas, United States, 78712

Lucid Investigative Site; Recruiting

Dallas, Texas, United States, 75246

Lucid Investigative Site; Recruiting

Houston, Texas, United States, 77030

United States, Utah

Lucid Investigative Site; Recruiting

Salt Lake City, Utah, United States, 84132

United States, Virginia

Lucid Investigative Site; Recruiting

Richmond, Virginia, United States, 23249

Lucid Investigative Site; Not yet recruiting

Richmond, Virginia, United States, 23298

Sponsors and Collaborators

Lucid Diagnostics, Inc.

Investigators

• Study Director: Randy B, MS; Lucid Diagnostics, Inc.

More Information

• Responsible Party: Lucid Diagnostics, Inc.
• ClinicalTrials.gov Identifier: NCT04295811
• Other Study ID Numbers: PR-0138 / EG-CL-102
• First Posted: March 5, 2020
• Last Update Posted: October 5, 2020
• Last Verified: October 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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.: Yes

Additional relevant MeSH terms:

Adenocarcinoma; Barrett Esophagus; Esophageal Neoplasms; Hyperplasia; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Pathologic Processes; Precancerous Conditions; Esophageal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Head and Neck Neoplasms