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.
