Digma System First in Human (FIH) Study

Official title

First-in-Human Pilot Study for the Evaluation of Digma Medical's Endoscopic Gastrointestinal Ablation Device (EGAD) in the Esophagus

Overview

Prospective, open-label, single-arm, early feasibility study (EFS) in 2 Patient cohorts: Cohort A - Dose finding / Dose response study in patients with various etiologies undergoing Esophagectomy and Cohort B - Patients with Barrett's Esophagus (BE) with Low-Grade Dysplasia (LDG) or High-Grade Dysplasia (HGD) without a visible (excisable) lesion. This is a pilot study which plan to enroll up to 5 eligible patients in the First Cohort (A) and up to 15 patients in the Second Cohort (B) of the study.

Detailed description

Study intervention means tha application of different doses of laser energy in the ablation of esophageal mucosa using the Digma System and the Endoscopic Gastrointestinal Ablation Device (EGAD) procedure (Cohort A) followed by application of the optimal dose for treatment of patients with BE with Low-Grade Dysplasia (LGD) or High-Grade Dysplasia (HDG) without a visible lesion (Cohort B).

EGAD is a proprietary, controlled laser ablation system for the treatment of endoluminal pathologies of the gastrointestinal tract. EGAD achieves high precision through a unique optical design that controls laser energy, beam size, wavelength, and focal plane. This allows for effective ablation that is limited to the mucosa of pre-selected regions of interest, avoiding a wider and deeper injury to healthy tissue. EGAD procedure can be performed safely in a standard endoscopy suite under direct endoscopic visualization. In this First-in-Human pilot feasibility study, we plan to assess the feasibility of EGAD for achieving mucosal ablation (1) in healthy esophageal tissue in patients undergoing esophagectomy for esophageal cancer or other indications (Barrett's mucosa may be ablated as well) - Cohort A; and (2) In patients with Barrett's Esophagus with low and/or high-grade dysplasia (BORN = Barrett´s Oesophagus-Related Neoplasia) without a visible (excisable) lesion - Cohort B.

Interventions

• Device Endoscopic Gastrointestinal Ablation Device (EGAD)
  Application of different doses of laser energy in the ablation of esophageal mucosa using the Digma System and the EGAD procedure (Cohort A) followed by application of the optimal dose for treatment of patients with BE with LGD or HDG without a visible lesion (Cohort B).

Primary outcome measures

• Cohort A: Incidence of severe immediate adverse events (AEs) [Time frame: Day 1, ESOPHAGECTOMY surgery]
• Cohort B: Incidence of immediate severe AE [Time frame: Day 1]
• Cohort B: Incidence of late severe AE [Time frame: 10-12 months follow-up, following each visit and procedure]
• Cohort A: Dose response effects of ablation on mucosal tissue [Time frame: Day 1, ESOPHAGECTOMY surgery]
• Cohort B: Eradication of dysplasia level and of visible segment of BE [Time frame: 10-12 months follow-up, at each follow-up visit]

Secondary outcome measures (10)

• Adverse events related to the procedure (Cohort A+B) [Time frame: Day 1]
• Maximal ablation depth (cohort A) [Time frame: Day 1, ESOPHAGECTOMY surgery]
• Maximal ablation volume (cohort A) [Time frame: Day 1, ESOPHAGECTOMY surgery]
• Dose response effect of treatment(s) on depth-of-penetration. (cohort A) [Time frame: Day 1, ESOPHAGECTOMY surgery]
• Assessment of collateral impact as assessed by histopathologic evaluation. [Time frame: 10-12 months follow-up or when eradication of BE is achieved]
• Rate of complete eradication of dysplasia (cohort B) [Time frame: 10-12 months follow-up]
• Rate of eradication of intestinal metaplasia. (cohort B) [Time frame: 10-12 months follow-up]
• Eradication of macroscopically visible segment of BE. [Time frame: 10-12 months follow-up]
• Assessments of lesion ablation - safe margin area. [Time frame: 10-12 months follow-up]
• Assessment of technical aspects of the procedure-time [Time frame: Day 1]

Eligibility criteria

Inclusion criteria

Cohort A:

• Male or Female ≥18 years of age at the time of consent.
• Scheduled to undergo esophagectomy for malignant or benign indications .
• Contain enough healthy (or with BE) tissue to be ablated (≥1cm) by for EGAD treatment.
• Capable of providing written informed consent.

Cohort B:

• Male or Female ≥18 and ≤ 70 years of age at the time of consent.
• Documented diagnosis of Barrett's Esophagus (BE) with LGD or HGD, confirmed by biopsy specimen analysis.
• No visible lesion in the esophagus (suitable for endoscopic resection).
• Scheduled to undergo Endoscopic eradication therapy (EET) procedure of Barrett's Esophagus (BE) with dysplasia.
• BE affected tissue length ≥1 cm and ≤ 5cm (as measured endoscopically).
• Capable of providing written informed consent.
• Willingness and ability to comply with follow-up requirements, including endoscopies and biopsies.
• Ability to tolerate and take oral proton pump inhibitor (PPI) medication.

Exclusion criteria

Cohort A:

• Severe medical comorbidities that preclude esophagectomy.
• Any medical or technical condition that may preclude endoscopy during surgical esophagectomy at the discretion of operating surgeon.
• Any previous procedures involving esophageal tissue resection or ablation.
• Patients with incomplete healing of tissue following radiation at the area-of-interest.
• Subjects undergoing (or having undergone) photodynamic therapy.
• Subjects of high surgical risk, in which any delay in the esophagectomy surgery may, in the option of the PI, increase the risk for to Adverse event (AE) / Serious Adverse event (SAE).
• Presence of esophageal stricture preventing passage of the endoscope or investigational catheter .
• Any anatomical abnormality (such as but not limited to, esophageal dilation) that, at the discretion of the investigator may preclude the laser ablation.
• Presence of esophageal varices in the esophagus.
• Presence of severe bleeding or severe inflammation at the time of endoscopy of EGAD.
• Female who is pregnant, breast-feeding or intends to become pregnant or is of childbearing potential and not using an adequate contraceptive method .
• Any disorder, which in the investigator's opinion might jeopardize participant's safety or compliance with the Clinical Investigation Plan (CIP).
• Patient refusal or inability to provide written informed consent.

Cohort B:

• Severe medical comorbidities that preclude endoscopy or multiple co-morbidities placing the patient at risk or otherwise unsuitable for trial participation .
• Previous radiotherapy in the chest.
• Previous Endoscopic Mucosal resection (EMR) / Endoscopic Submucosal Dissection (ESD) in the esophagus.
• Subjects currently undergoing or subject that had previous ablative therapy within the esophagus (e.g., Photodynamic Therapy (PDT), Multipolar Electrocoagulation (MPEC), Argon Plasma Coagulation (APC), laser treatment, radiofrequency ablation (RFA).
• Presence of esophageal stricture preventing passage of the endoscope or investigational catheter .
• Active esophagitis.
• Esophageal or gastric varices.
• Subject diagnosed with portal hypertension.
• Subject diagnosed with Liver cirrhosis.
• Presence of severe bleeding or severe inflammation in the area-of-interest.
• Use of anticoagulants or antiplatelet agents that cannot be discontinued 5 days prior to the procedure
• Active systemic infection or malignancy.
• History of esophagectomy
• History of locally advanced (>T1a) esophageal cancer treated endoscopically/by chemoradiotherapy.
• Subjects with known coagulation conditions (e.g. uncontrolled coagulopathy)
• Concurrent chemotherapy.
• Female who is pregnant, breast-feeding or intends to become pregnant or is of childbearing potential and not using an adequate contraceptive method.
• Any disorder, which in the investigator's opinion might jeopardize participant's safety or compliance with the CIP .
• Patient refusal or inability to provide written informed consent.
• Known history of unresolved drug or alcohol dependency that would limit ability to comprehend or follow instructions, uncontrolled psychiatric illness (including recent inpatient psychiatric treatment, psychosis, moderate to severe depression, illicit substance abuse) or any psychiatric diagnosis which in the opinion of the investor would preclude participation in the study.
• Concurrent enrollment in an investigational drug or device trial that clinically interferes with study endpoints.
• Subject that is unwilling or unable to comply with study visits and other study procedures as required per protocol.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Czechia · 1 center

• Fakultní nemocnice u sv. Anny v Brně, Gastroenterologické a hepatologické oddělení — Brno

Identifiers

NCT: NCT07331857 · CLD-014-BE

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗