Overview

Cellspan™ Esophageal Implant-Adult (CEI)

The CEI is a combination product consisting of an engineered synthetic scaffold (device constituent) seeded and cultured with the patient's adipose derived mesenchymal stem cells (biologic constituent), intended to stimulate regeneration of a structurally intact, living biologic esophageal conduit, in patients requiring full circumferential esophageal reconstruction up to 6 cm segment in length.

This is a single arm, unblinded, multicenter, prospective first-in-human (FIH) feasibility study to be performed at a maximum of 5 centers in the United States with a maximum of 10 subjects in total. All subjects will be followed for a minimum of 2 years post-implant surgery.

Since this is an FIH experience, the study will utilize an independent Data Monitoring Committee (DMC) to evaluate safety on a continuous basis to mitigate any safety risks to subjects. A sentinel approach to enrollment of subjects shall be guided by the DMC review of cases.

Eligibility

Inclusion Criteria:

1. Subject ≥18 years of age
2. The patient has medical conditions requiring esophageal reconstruction, such as, but not limited to:
   1. Refractory benign esophageal strictures (RBES)
   2. Esophageal perforation (full thickness)
   3. Chronic/persistent esophageal fistula
   4. Combination of esophageal perforations/fistula with RBES
3. The patient must have failed at least 3 previous treatment modalities to correct the

   medical esophageal condition (a-d).

   1. If RBES: i. Steroid treatment ii. Esophageal balloon dilation (EBD) iii. Stent use >6 months iv. Endoscopic incisional repair
   2. If esophageal perforation: i. Fibrin glue ii. Endoscopic clips and/or suturing iii. Stent > 6 months iv. Primary surgical repair
   3. If Chronic/Persistent fistula(e): i. Fibrin glue ii. Endoscopic clips and/or suturing iii. Stent > 6 months iv. Primary surgical repair
   4. If Combination Perforation/fistula with RBES i. Fibrin glue ii. Endoscopic clips and/or suturing iii. Stent use > 6 months iv. Primary surgical repair
4. The patient must be a surgical candidate for a short segment esophageal reconstruction

   (<6 cm full circumferential segmental excision)

5. The location of the esophageal segment for surgical resection is within the thoracic cavity, defined as above the diaphragm and at least 4 cm below the larynx.
6. Patient must be a high-risk candidate for minimally invasive esophageal reconstruction, based upon the investigator's determination (For example, laparoscopic gastric pull-up (GPU) is not an option due to a medical contraindication)
7. All patients must be made aware and must be amenable to a delayed rescue repair surgical procedure in the event the CEI fails to restore a patent durable biologic esophageal conduit

Exclusion Criteria:

1. Pre-existing implants/structures adjacent to target surgical location for implant that could cause abrasion of the scaffold/regenerated tissue (e.g., pacemaker lead, vascular clips, vascular grafts).
2. Known clinical contraindication that would obfuscate the use of the covered metallic stent to be used as an adjunct to the procedure
3. Post ablation stricture for Barrett's esophagus treated less than 1 year prior to planned procedure
4. Patient has a comorbidity or contraindication that would preclude any study required procedures including adipose tissue biopsy and esophageal resection surgery. Comorbidities are defined from a subset of the Charlson Comorbidities Index (CCI, Yamashita 2018) scoring system and include:
   1. diabetes mellitus (CCI = 1)
   2. connective tissue disorders (CCI=1)
   3. immune compromised
   4. chemotherapy (within 60 day clearance)
   5. inability to tolerate major thoracotomy
   6. active infection at the biopsy or thoracotomy incision site
   7. peripheral vascular disease (CCI=1)
   8. all patients with a CCI> 2
5. Life expectancy of less than 1 year