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

Tracheal Stenosis Clinical Trial

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

Clinical Trial Details — Status: Suspended

Administrative data

• NCT number: NCT02949414
• Other study ID #: D-00173-CT2013002
• Status: Suspended
• Phase: Phase 1
• First received: January 15, 2016
• Last updated: March 28, 2018
• Start date: September 2016
• Est. completion date: September 2024

Study information

• Verified date: March 2018
• Source: Cell Therapy Catapult
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Suspended
• Enrollment: 4
• Est. completion date: September 2024
• Est. primary completion date: September 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Constriction, Pathologic
• Tracheal Stenosis
• Tracheomalacia

Intervention

Procedure:
• Cadaveric decellularised tracheal scaffold seeded with autologous mesenchymal cells
The tracheal graft will be manufactured from cadaveric tracheal scaffold and bone marrow derived mesenchymal cells.

Locations

Country	Name	City	State
United Kingdom	Royal Nose Throat and Ear Institute	London

Sponsors (3)

Lead Sponsor	Collaborator
Cell Therapy Catapult	University College, London, Videregen

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Changes in Quality of Life assessed using EQ-5D questionnaires		Up to 5 years post graft.
Other	Change in Airway Dyspnoea Voice swallowing Index (ADVS)		Up to 5 years post graft.
Other	Medical Resource Utilisation (MRU) assessed by number and type of tracheal related procedures and treatments post tracheal replacement.		Up to 5 years post graft.
Other	Change in maximum phonation time (MPT) measured in seconds		Up to and including 5 years post graft
Primary	Number of treatment related SAE's as assessed by CTCAE grades as defined in version 4.0		Up to 8 months post graft
Secondary	Efficacy: Post Implant Stent free period		Up to 5 years post implant
Secondary	Efficacy: Post Implant Tracheostomy free period	Absence of other surgical interventions	Up to 5 years post implant
Secondary	Efficacy: Mean Airway Diameter evaluations as captured by CT scans		Up to 5 years post implant
Secondary	Efficacy: Changes in lung function results using a combination of FEV1, FEF50 and PEFR results		Up to 5 years post implant
Secondary	Number of treatment related AEs as assessed by CTCAE grading version 4.0		Upto 5 years post implant