RecruitingPhase 1NCT05877300

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

Sponsor

Harvard Apparatus Regenerative Technology, Inc.

Enrollment

10 participants

Start Date

Jul 13, 2023

Study Type

INTERVENTIONAL

Conditions

Esophageal Diseases

Summary

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 dual 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

Min Age: 18 Years

Inclusion Criteria26

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 use ≥ 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, above the diaphragm and at least 4 cm below the larynx.
The patient must be a high-risk candidate for minimally invasive esophageal reconstruction, based upon the investigator's determination. The patient requires a thoracotomy to repair the esophagus and is not amenable for laparoscopic or robotic minimally invasive gastric pull-up (GPU) surgery, 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
The patient/guardian is willing and able to comply with the protocol specified medication regimen and follow-up evaluations
The patient/guardian has been informed of the nature of the study, agrees to its provisions, and has provided written informed consent approved by the appropriate Institutional Review Board (IRB) or Ethics Committee (EC)
Subject ≥18 years of age
The patient has medical conditions requiring esophageal reconstruction, limited to:
a. Spit Fistula with an upper esophageal ostomy in the neck
Patients may require esophageal de-functioning with a resulting cervical spit fistula if they are not candidates for immediate esophageal reconstruction. This may occur for multiple reasons, including being too sick for reconstruction, healing of the airway after tracheo-esophageal fistula repair, requirement for further therapy prior to reconstruction, or recovering from sepsis due to esophageal perforation.
The patient must be a surgical candidate for a short segment esophageal reconstruction (\< 7cm), a full circumferential segmental esophageal extension in order to have sufficient length to make the anastomosis to the distal thoracic esophagus, to a gastric or to an intestinal interposition conduit that will re-establish oral nutritional intake. i.
Patient must be a high-risk candidate for the standard of care treatment of esophageal reconstruction, based upon the investigator's determination. The patient requires a thoracotomy to repair the esophagus following the CEI subdermal extension procedure and is not amenable for laparoscopic or robotic minimally invasive gastric pull-up (GPU) surgery.
All patients must be made aware and must be amenable to a delayed rescue repair surgical procedure in the event the CEI fails to mature in the subdermal area prior to mobilization
The patient/guardian is willing and able to comply with the protocol- specified medication regimen and follow-up evaluations
The patient/guardian has been informed of the nature of the study, agrees to its provisions, and has provided written informed consent approved by the appropriate Institutional Review Board (IRB) or Ethics Committee (EC).

Exclusion Criteria23

Subject requires or undergoes an esophageal segmental excision \>6 cm in length
Esophageal segment extends below the diaphragm or \<4 cm below larynx
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 radiotherapy or chemoradiotherapy (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
Pregnant or nursing patients and those who plan pregnancy in the period up to 1 year following the index procedure. Female patients of childbearing potential must have a negative pregnancy test (per site standard test) within 7days prior to index procedure.
Has a known untreated neurological, psychological, psychiatric, or other disorder that would interfere with trial endpoints or with cooperation with the requirements of the trial
Has a diagnosis of immunodeficiency, receiving cancer therapy including chimeric antigen receptor T cells (CAR-T), receiving systemic steroid therapy (\>10 mg prednisone or equivalent daily dose), or any other form of pharmacologic therapy that would inhibit the intended cell growth (e.g., protease inhibitors, immunosuppressants, anti-cytokine therapies) within 30 days prior to index procedure or intended for use during any time after implantation through 12 months post-index procedure.
Patient with an infection requiring antibiotic therapy
Known allergy to Nitinol (for adjunctive self-expanding covered metallic stent procedure)
Current participation in another investigational drug or device study
Patient is a prisoner
If in the opinion of the investigator, the patient requires pain management (potentially opioid medications) as a result of study participation, the patient is at an unreasonable risk of addiction. This decision may be based upon medical or social history, personal situation, or the expected time course, length, and type of medication use.

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Interventions

COMBINATION_PRODUCTCEI Thoracic Surgical Implantation-Cellspan™ Esophageal Implant-Adult (CEI) in patients requiring a full reconstruction of the esophagus

The CEI will be surgically implanted using standard thoracotomy techniques for esophageal reconstruction. Day 0 procedures include: a short segment esophageal resection up to 6 cm, CEI implantation with end-to-end anastomosis, placement of a covered metallic stent, securing the stent with sutures, measuring and recording the stent position, placing draining catheters, inserting a dual lumen gastric-jejunal feeding tube, and conducting hematology and serum tests. A baseline CT/MRI scan will be performed post-surgery to check the anastomotic sites and stent placement.

COMBINATION_PRODUCTCEI Extra-Thoracic Subdermal Surgical Implantation - Cellspan™ Esophageal Implant-Adult (CEI) in patients that have had a previous partial esophagectomy

For CEI grafts extending the upper esophagus from the neck ostomy, the patient is positioned supine to expose the left neck and upper chest. A neck incision is made medial to the sternocleidomastoid muscle. The distal esophagus at the cervical spit fistula is freed and mobilized. The CEI is connected to the mobilized esophageal segment with absorbable sutures. Photos document the new spit fistula length post-graft. A new spit fistula tunnel is created on the anterior chest wall, preserving skin and tissue. A covered metallic stent is placed endoscopically through the spit fistula into the CEI, secured with sutures. Pre-surgery tests include hematology, serum chemistry, urinalysis, and CRP, with CRP checked on Days 3 and 5 post-surgery. A CT or MRI scan is done on days 3-7 post-surgery to establish a baseline for tissue deposition analysis around the CEI.