Esophageal Implant for Esophageal Reconstruction

Recruiting at 1 trial location

Overseen By William L Fodor, Ph.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Biostage, Inc.

Disqualifiers: Diabetes, Connective tissue disorders, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

10 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

What data supports the effectiveness of the treatment Cellspan Esophageal Implant (CEI) for esophageal reconstruction?

Research in animal models, like pigs, shows that the Cellspan Esophageal Implant (CEI) can help the esophagus regrow and heal after part of it is removed. The new tissue becomes strong and similar to the original esophagus over time, allowing normal eating and growth. ^{1 2 3 4 5}

Is the Cellspan Esophageal Implant safe for humans?

The Cellspan Esophageal Implant has been used in a human case under FDA Expanded Access Use, and studies in animal models have shown it supports tissue regeneration and long-term survival, suggesting it is generally safe. ^{1 2 3 4 6}

How is the Cellspan Esophageal Implant treatment different from other esophageal reconstruction treatments?

The Cellspan Esophageal Implant is unique because it uses a bioengineered implant seeded with the patient's own cells to stimulate the regrowth and regeneration of the esophagus, unlike traditional methods that may involve more invasive surgeries or synthetic materials. This approach aims to restore the esophagus by promoting natural tissue regeneration, potentially reducing complications and improving outcomes. ^{1 2 3 4 7}

What is the purpose of this trial?

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 Criteria

This trial is for adults over 18 who've tried at least three treatments without success for esophageal conditions like strictures, perforations, or fistulas. They must need and be able to undergo a short segment esophageal reconstruction within the thoracic cavity and be considered high-risk for standard procedures.

Inclusion Criteria

I have tried at least 3 treatments for my esophagus condition without success.

I am eligible for a surgery to remove a small part of my esophagus.

I need surgery to fix my esophagus due to severe damage or blockage.

Exclusion Criteria

I had a procedure for Barrett's esophagus less than a year ago.

I have implants near the surgery area that could interfere with the healing.

Life expectancy of less than 1 year

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Implantation and Initial Monitoring

Participants undergo the CELLSPAN Esophageal Implant procedure and are monitored for immediate post-surgical outcomes

6 weeks

Regular monitoring visits

Follow-up

Participants are monitored for safety and effectiveness after treatment, including imaging and endoscopic evaluations

3 months

Monthly visits

Long-term Follow-up

Participants are followed for a minimum of 2 years post-implant surgery to assess long-term safety and efficacy

2 years

Treatment Details

Interventions

• Cellspan™ Esophageal Implant (CEI)

Trial Overview The study tests the CELLSPAN Esophageal Implant (CEI), which uses a patient's stem cells on a synthetic scaffold to regenerate part of the esophagus. It's a first-in-human trial with continuous safety monitoring by an independent committee across multiple U.S. centers.

Participant Groups

Group I: Short Segment Esophageal Replacement Experimental Treatment 1 Intervention

Cellspan™ Esophageal Implant (CEI) is already approved in United States, European Union for the following indications:

Approved in United States as Cellspan Esophageal Implant for:

• Short segment esophageal replacement
• Refractory benign esophageal strictures (RBES)
• Esophageal perforation
• Chronic/persistent esophageal fistula

Approved in European Union as Cellspan Esophageal Implant for:

• Orphan designation for esophageal reconstruction

Who Is Running the Clinical Trial?

Biostage, Inc.

Lead Sponsor

Trials

1

Recruited

10+

Harvard Apparatus Regenerative Technology, Inc.

Lead Sponsor

Trials

1

Recruited

10+

Findings from Research

A patient successfully received a tissue-engineered esophageal graft made from autologous adipose-derived mesenchymal stromal cells (Ad-MSCs) and a polyurethane scaffold, demonstrating the potential for esophageal regeneration after a complex tumor resection.

Histological analysis 7.5 months post-implantation showed complete luminal epithelialization and partial regeneration of esophageal tissue, indicating that the graft effectively supports healing and tissue growth.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-in-Human Segmental Esophageal Reconstruction Using a Bioengineered Mesenchymal Stromal Cell-Seeded Implant. Aho, JM., La Francesca, S., Olson, SD., et al.[2022]

The CellspanTM Esophageal Implant (CEI) successfully stimulated tissue regeneration in a porcine model after segmental resection of the esophagus, leading to a fully epithelialized lumen by 90 days and complete tissue architecture restoration by 365 days.

The mechanical strength of the regenerated tissue was comparable to that of the native esophagus, indicating that the CEI not only facilitated healing but also restored the functional integrity of the esophagus over time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biomechanics of regenerated esophageal tissue following the implantation of a tissue engineered CellspanTM Esophageal Implant. Meng, L., Frohbergh, M., Villarraga, M., et al.[2022]

The Cellspan Esophageal ImplantTM (CEI) was successfully implanted in piglets, showing promising results in restoring esophageal continuity with complete epithelialization of the lumenal surface by day 90 and ongoing tissue remodeling over a 1-year period.

CT imaging and histological evaluations confirmed the safety and efficacy of the CEI, as it allowed for normal growth and restoration of oral nutrition in the animals, indicating a viable alternative to traditional surgical interventions for esophageal defects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Esophageal regeneration following surgical implantation of a tissue engineered esophageal implant in a pediatric model. Sundaram, S., Jensen, T., Roffidal, T., et al.[2022]

This study successfully created tissue-engineered esophageal constructs using cells isolated from donor rat esophagus, which were cultured and integrated into the host tissue after transplantation, allowing recipients to resume normal feeding.

The engineered constructs demonstrated the ability to develop into multiple cell types (epithelial, smooth muscle, and glial), indicating their potential for treating severe esophageal conditions in both pediatric and adult patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biomimetic and synthetic esophageal tissue engineering. Jensen, T., Blanchette, A., Vadasz, S., et al.[2018]

A novel esophageal substitute made from a decellularized porcine scaffold seeded with bone marrow-derived mesenchymal stromal cells (BM-MSCs) showed promising results in replicating the muscle layer of the esophagus, indicating potential for functional restoration.

Despite some complications like esophageal substenosis in both non-seeded and seeded groups, the seeded scaffolds demonstrated better muscle layer regeneration, suggesting that cell seeding enhances the healing process compared to non-seeded scaffolds.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful muscle regeneration by a homologous microperforated scaffold seeded with autologous mesenchymal stromal cells in a porcine esophageal substitution model. Marzaro, M., Algeri, M., Tomao, L., et al.[2022]

Iodine-125 seed implantation demonstrated a 100% dysphagia remission rate at half a month post-treatment, significantly outperforming conventional treatments like radiotherapy and chemotherapy, which had much lower remission rates.

No serious adverse events were reported with iodine-125 seed implantation, indicating it is a safer option compared to conventional therapies that had higher incidences of myelosuppression and gastrointestinal side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of the Therapeutic Effects of Iodine-125 Seed Implantation and Conventional Radiochemotherapy for Advanced Esophageal Cancer. Han, LQ., Wang, CH., Cui, TT., et al.[2022]

Tissue engineering offers a promising alternative to traditional esophageal replacement methods by using a combination of acellular matrices and autologous cells, showing the most success in creating esophageal substitutes.

Future developments may include 'intelligent matrices' that promote tissue regeneration without the need for implantation, leveraging the properties of mesenchymal stem cells to enhance healing and reduce inflammation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Esophageal tissue engineering: Current status and perspectives. Poghosyan, T., Catry, J., Luong-Nguyen, M., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

First-in-Human Segmental Esophageal Reconstruction Using a Bioengineered Mesenchymal Stromal Cell-Seeded Implant. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Biomechanics of regenerated esophageal tissue following the implantation of a tissue engineered CellspanTM Esophageal Implant. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Esophageal regeneration following surgical implantation of a tissue engineered esophageal implant in a pediatric model. [2022]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Biomimetic and synthetic esophageal tissue engineering. [2018]

5. England pubmed.ncbi.nlm.nih.gov

Successful muscle regeneration by a homologous microperforated scaffold seeded with autologous mesenchymal stromal cells in a porcine esophageal substitution model. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Comparison of the Therapeutic Effects of Iodine-125 Seed Implantation and Conventional Radiochemotherapy for Advanced Esophageal Cancer. [2022]

7. France pubmed.ncbi.nlm.nih.gov

Esophageal tissue engineering: Current status and perspectives. [2022]