A Study to Assess the Safety, Tolerability and Potential Efficacy of a Tracheal Replacement Consisting of a Tissue-engineered Tracheal Scaffold With Seeded Mesenchymal Cells

March 28, 2018 updated by: Cell Therapy Catapult

A Phase I Open-label Study to Assess the Safety, Tolerability and Potential Efficacy of a Novel Tracheal Replacement Consisting of a Tissue-engineered Decellularised Tracheal Scaffold With Seeded Autologous Mesenchymal Cells in Subjects With Severe Tracheal Stenosis or Malacia

This is a phase I study to evaluate the safety, efficacy and tolerability of a novel tracheal replacement therapy using cadaveric de-cellularised tracheal scaffold and patients' own mesenchymal cells isolated from a sample of their bone marrow in patients' who suffer from severe tracheal malacia or stenosis.

Study Overview

Detailed Description

This is a phase I study to evaluate the safety, tolerability and potential efficacy of a novel tracheal replacement therapy using a cadaveric tracheal scaffold and patients own mesenchymal cells isolated from a sample of the patients own bone marrow. The study is aimed at treating patients who suffer from severe tracheal stenosis or malacia and for whom conventional therapies are no longer adequate. A total of 4 patients will be treated during the course of this study.

A hospital multi disciplinary team will review the medical history and available treatment options for all potential patients and recommend whether they are suitable for the study. Once patients are approved they will enter an 8 week screening period. During this period bone marrow from the patient will be harvested and the manufacturing of the final graft tissue will start. The manufacturing facility will use a cadaveric donated decellularised tracheal scaffold (supplied by the NHS blood and transplant body) and the patients own cells to make the final investigational product (graft).

The product will be surgically grafted into the patient in place of the damaged tracheal section. The graft will be supported by a stent for the first 6 months with replacements of this stent occurring at week 8 and week 16 post-surgical procedure. Hospitalization for a number of days will be required during this replacement steps. The patient will be followed frequently post surgery to capture any safety and efficacy measures. Long term follow up will continue up to 5 years post surgery.

Study Type

Interventional

Enrollment (Anticipated)

4

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • London, United Kingdom, WC1X 8DA
        • Royal Nose Throat and Ear Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Male or female subjects 18 years or older (all subjects must provide written informed consent)
  • Stent or tracheostomy dependent diagnosis of tracheal stenosis or tracheomalacia (Cotton-Myers grade 2 or more)
  • Subjects in the above categories for whom further conventional therapies are no longer adequate

Exclusion Criteria:

  • Pregnancy
  • Subjects unable to provide informed consent
  • Prior tracheal transplant
  • No viable bone marrow cells within the screening period
  • Subjects who have conventional treatment options still available that may have additive impact
  • Subject diagnosed or treated for a malignancy within 1 year of study entry or who have previously been diagnosed with a malignancy and have any radiographic or biochemical biomarker evidence of malignancy. Subjects with completely resected basal cell carcinoma or squamous cell carcinoma of the skin or in situ malignancy are not excluded
  • Subject with active inflammatory or infectious conditions such as polychondritis, granulomatosis with polyangiitis ('Wegener's'), sarcoidosis or tuberculosis
  • Co-morbid moderate or severe chronic obstructive pulmonary disease (COPD) as defined in Global Initiative for COPD, 2011 2, that is unrelated to tracheal stenosis or malacia
  • Subjects with known presence of human immunodeficiency virus (HIV) antibody, Hepatitis B surface antigen (HbsAG) or Hepatitis C antibody
  • Subject with clinically relevant or recent (within 2 years) history of substance abuse, including alcohol
  • Serious medical or psychiatric illness likely to interfere with participation in the study
  • Participation in any other clinical trial within previous 30 days of the start of this study or concurrent participation in another clinical trial.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Tracheal Replacement
Each patient will receive surgery to implant the cadaveric decellularised tracheal scaffold seeded with autologous mesenchymal cells and all follow-up procedures.
The tracheal graft will be manufactured from cadaveric tracheal scaffold and bone marrow derived mesenchymal cells.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Number of treatment related SAE's as assessed by CTCAE grades as defined in version 4.0
Time Frame: Up to 8 months post graft
Up to 8 months post graft

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Efficacy: Post Implant Stent free period
Time Frame: Up to 5 years post implant
Up to 5 years post implant
Efficacy: Post Implant Tracheostomy free period
Time Frame: Up to 5 years post implant
Absence of other surgical interventions
Up to 5 years post implant
Efficacy: Mean Airway Diameter evaluations as captured by CT scans
Time Frame: Up to 5 years post implant
Up to 5 years post implant
Efficacy: Changes in lung function results using a combination of FEV1, FEF50 and PEFR results
Time Frame: Up to 5 years post implant
Up to 5 years post implant
Number of treatment related AEs as assessed by CTCAE grading version 4.0
Time Frame: Upto 5 years post implant
Upto 5 years post implant

Other Outcome Measures

Outcome Measure
Time Frame
Changes in Quality of Life assessed using EQ-5D questionnaires
Time Frame: Up to 5 years post graft.
Up to 5 years post graft.
Change in Airway Dyspnoea Voice swallowing Index (ADVS)
Time Frame: Up to 5 years post graft.
Up to 5 years post graft.
Medical Resource Utilisation (MRU) assessed by number and type of tracheal related procedures and treatments post tracheal replacement.
Time Frame: Up to 5 years post graft.
Up to 5 years post graft.
Change in maximum phonation time (MPT) measured in seconds
Time Frame: Up to and including 5 years post graft
Up to and including 5 years post graft

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Martin Birchall, MD, PhD, University College, London

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2016

Primary Completion (Anticipated)

September 1, 2019

Study Completion (Anticipated)

September 1, 2024

Study Registration Dates

First Submitted

January 15, 2016

First Submitted That Met QC Criteria

October 27, 2016

First Posted (Estimate)

October 31, 2016

Study Record Updates

Last Update Posted (Actual)

March 29, 2018

Last Update Submitted That Met QC Criteria

March 28, 2018

Last Verified

March 1, 2018

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

Study and analysis will be published upon completion.

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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