Safety and Feasibility Study of the CELLSPAN Esophageal Implant (CEI) in Patients Requiring Short Segment Esophageal Replacement

Study Overview
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Brief Summary
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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.

Official Title
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Safety and Feasibility Study of the CELLSPAN Esophageal Implant (CEI) in Patients Requiring Short Segment Esophageal Replacement

Conditions
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Esophageal Diseases

Intervention / Treatment
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* Combination Product: Cellspan™ Esophageal Implant-Adult (CEI)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject ≥18 years of age The patient has medical conditions requiring esophageal reconstruction, such as, but not limited to: Refractory benign esophageal strictures (RBES) Esophageal perforation (full thickness) Chronic/persistent esophageal fistula Combination of esophageal perforations/fistula with RBES The patient must have failed at least 3 previous treatment modalities to correct the medical esophageal condition (a-d). a. If RBES: i. Steroid treatment ii. Esophageal balloon dilation (EBD) iii. Stent use >6 months iv. Endoscopic incisional repair b. If esophageal perforation: i. Fibrin glue ii. Endoscopic clips and/or suturing iii. Stent > 6 months iv. Primary surgical repair c. If Chronic/Persistent fistula(e): i. Fibrin glue ii. Endoscopic clips and/or suturing iii. Stent > 6 months iv. Primary surgical repair d. If Combination Perforation/fistula with RBES i. Fibrin glue ii. Endoscopic clips and/or suturing iii. Stent use > 6 months iv. Primary surgical repair The patient must be a surgical candidate for a short segment esophageal reconstruction (<6 cm full circumferential segmental excision) The location of the esophageal segment for surgical resection is within the thoracic cavity, defined as, at least 4 cm above gastroesophageal junction (GEJ) and at least 4 cm below the larynx 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) 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: 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). Known clinical contraindication that would obfuscate the use of the covered metallic stent to be used as an adjunct to the procedure Post ablation stricture for Barrett's esophagus treated less than 1 year prior to planned procedure 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: diabetes mellitus (CCI = 1) connective tissue disorders (CCI=1) immune compromised chemotherapy (within 60 day clearance) inability to tolerate major thoracotomy active infection at the biopsy or thoracotomy incision site peripheral vascular disease (CCI=1) all patients with a CCI> 2 Life expectancy of less than 1 year

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Short Segment Esophageal Replacement<br> | Combination Product: Cellspan™ Esophageal Implant-Adult (CEI)<br>* The CEI is a combination product consisting of an engineered synthetic scaffold (device constituent) seeded and cultured with the patient's adipose derived mesenchymal stromal 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The number of patients who develops continuous biologic neo-conduit within the esophagus based on CT/MRI imaging and visual endoscopic evaluation. | The number of patients who develops continuous biologic neo-conduit within the esophagus based on CT/MRI imaging and visual endoscopic evaluation, prior to or at Month 3 visit (Day 77 ±10) following implantation. | Month 3 | 
| The number of patients who does not develop anastomotic leak or fistula that requires non-endoscopic therapy. | The number of patients who does not develop anastomotic leak or fistula that requires non-endoscopic therapy. | 42 days | 
| The number of patients within the first 42 days that do not require a fall back emergency esophagectomy procedure | The number of patients within the first 42 days that do not require a fall back emergency esophagectomy procedure (gastric pull-up, colonic interposition, or other surgical reconstruction). | 42 days | 
| Number of participants experiencing death within 30 days of index procedure | Number of participants experiencing death within 30 days of index procedure | Within 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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FIH, Esophagus, Esophagectomy, Tissue Engineering, Organ Regeneration, Regenerative Medicine, Cell Therapy, Single Arm, Unblinded, Multicenter, CEI, Biostage