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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

Primary Purpose

Tracheomalacia, Tracheal Stenosis

Status

Suspended

Phase

Phase 1

Locations

United Kingdom

Study Type

Interventional

Intervention

Cadaveric decellularised tracheal scaffold seeded with autologous mesenchymal cells

About this trial

This is an interventional treatment trial for Tracheomalacia focused on measuring Malacia, Stenosis, Trachea, Transplant

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Royal Nose Throat and Ear Institute

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Tracheal Replacement

Arm Description

Each patient will receive surgery to implant the cadaveric decellularised tracheal scaffold seeded with autologous mesenchymal cells and all follow-up procedures.

Outcomes

Primary Outcome Measures

Number of treatment related SAE's as assessed by CTCAE grades as defined in version 4.0

Secondary Outcome Measures

Efficacy: Post Implant Stent free period

Efficacy: Post Implant Tracheostomy free period

Absence of other surgical interventions

Efficacy: Mean Airway Diameter evaluations as captured by CT scans

Efficacy: Changes in lung function results using a combination of FEV1, FEF50 and PEFR results

Number of treatment related AEs as assessed by CTCAE grading version 4.0

Full Information

NCT ID

NCT02949414

First Posted

January 15, 2016

Last Updated

March 28, 2018

Sponsor

Cell Therapy Catapult

Collaborators

University College, London, Videregen Limited

1. Study Identification

Unique Protocol Identification Number

NCT02949414

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2018

Overall Recruitment Status

Suspended

Study Start Date

September 2016 (undefined)

Primary Completion Date

September 2019 (Anticipated)

Study Completion Date

September 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Cell Therapy Catapult

Collaborators

University College, London, Videregen Limited

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Tracheomalacia, Tracheal Stenosis

Keywords

Malacia, Stenosis, Trachea, Transplant

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

4 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Tracheal Replacement

Arm Type

Experimental

Arm Description

Each patient will receive surgery to implant the cadaveric decellularised tracheal scaffold seeded with autologous mesenchymal cells and all follow-up procedures.

Intervention Type

Procedure

Intervention Name(s)

Cadaveric decellularised tracheal scaffold seeded with autologous mesenchymal cells

Intervention Description

The tracheal graft will be manufactured from cadaveric tracheal scaffold and bone marrow derived mesenchymal cells.

Primary Outcome Measure Information:

Title

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

Secondary Outcome Measure Information:

Title

Efficacy: Post Implant Stent free period

Time Frame

Up to 5 years post implant

Title

Efficacy: Post Implant Tracheostomy free period

Description

Absence of other surgical interventions

Time Frame

Up to 5 years post implant

Title

Efficacy: Mean Airway Diameter evaluations as captured by CT scans

Time Frame

Up to 5 years post implant

Title

Efficacy: Changes in lung function results using a combination of FEV1, FEF50 and PEFR results

Time Frame

Up to 5 years post implant

Title

Number of treatment related AEs as assessed by CTCAE grading version 4.0

Time Frame

Upto 5 years post implant

Other Pre-specified Outcome Measures:

Title

Changes in Quality of Life assessed using EQ-5D questionnaires

Time Frame

Up to 5 years post graft.

Title

Change in Airway Dyspnoea Voice swallowing Index (ADVS)

Time Frame

Up to 5 years post graft.

Title

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.

Title

Change in maximum phonation time (MPT) measured in seconds

Time Frame

Up to and including 5 years post graft

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Martin Birchall, MD, PhD

Organizational Affiliation

University College, London

Official's Role

Principal Investigator

Facility Information:

Facility Name

Royal Nose Throat and Ear Institute

City

London

ZIP/Postal Code

WC1X 8DA

Country

United Kingdom

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

Study and analysis will be published upon completion.

Learn more about this trial

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

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