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

• ClinicalTrials.gov Identifier: NCT02949414
• Recruitment Status: Suspended
• First Posted: October 31, 2016
• Last Update Posted: March 29, 2018
• Sponsor: Cell Therapy Catapult
• Collaborators: University College, London; Videregen Limited
• Information provided by (Responsible Party): Cell Therapy Catapult

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.

Condition or disease	Intervention/treatment	Phase
Tracheomalacia; Tracheal Stenosis	Procedure: Cadaveric decellularised tracheal scaffold seeded with autologous mesenchymal cells	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 4 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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 Start Date: September 2016
• Estimated Primary Completion Date: September 2019
• Estimated Study Completion Date: September 2024

Arms and Interventions

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.	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.

Outcome Measures

Primary Outcome Measures :

1. 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 Measures :

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

Other Outcome Measures:

1. Changes in Quality of Life assessed using EQ-5D questionnaires [ Time Frame: Up to 5 years post graft. ]
2. Change in Airway Dyspnoea Voice swallowing Index (ADVS) [ Time Frame: Up to 5 years post graft. ]
3. 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. ]
4. Change in maximum phonation time (MPT) measured in seconds [ Time Frame: Up to and including 5 years post graft ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United Kingdom

Royal Nose Throat and Ear Institute

London, United Kingdom, WC1X 8DA

Sponsors and Collaborators

Cell Therapy Catapult

University College, London

Videregen Limited

Investigators

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

More Information

• Responsible Party: Cell Therapy Catapult
• ClinicalTrials.gov Identifier: NCT02949414
• Other Study ID Numbers: D-00173-CT2013002
• First Posted: October 31, 2016
• Last Update Posted: March 29, 2018
• Last Verified: March 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Study and analysis will be published upon completion.

Keywords provided by Cell Therapy Catapult:

Malacia; Stenosis; Trachea; Transplant

Additional relevant MeSH terms:

Tracheomalacia; Tracheal Stenosis; Constriction, Pathologic; Pathological Conditions, Anatomical; Tracheal Diseases; Respiratory Tract Diseases; Tracheobronchomalacia; Cartilage Diseases; Musculoskeletal Diseases; Musculoskeletal Abnormalities; Congenital Abnormalities; Connective Tissue Diseases