Back to resultsENgineered Tissue Repair of BronchopleUral fiSTula (ENTRUST)
Primary Purpose
Bronchopleural Fistula
Status
Not yet recruiting
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
BPF-001
Sponsored by
About this trial
This is an interventional treatment trial for Bronchopleural Fistula
Eligibility Criteria
Inclusion Criteria:
- Male or female subjects 18 years or older.
- Documented diagnoses of BPF through imaging and bronchoscopic examination.
- BPF which involves the tracheobronchial junction or proximal bronchus.
- Subjects who have failed primary repair.
- Subjects who have no evidence of any primary or recurrent cancer (not limited to the surgical site) at the time of pre-operative screening as evidenced by CT and/or targeted biopsy (except for controlled or controllable basal cell carcinoma.
- Subjects who have signed and dated written informed consent to participate in the study.
- Females of childbearing potential (i.e. not surgically sterilised or post-menopausal for at least 2 years) must have a negative serum or urine pregnancy test.
- Male and female subjects of childbearing potential (i.e. not surgically sterilised or post-menopausal for at least 2 years) must use forms of highly effective methods of contraception, which are defined as hormonal methods of contraception (oral, injection or implant), barrier methods (condom or occlusive cap (diaphragm or cervical/vault caps)) with spermicidal foam/gel/cream/film/suppository, or true abstinence for 1 month following surgery.
- Subjects who have produced viable cells from Bone Marrow Aspirate.
Exclusion Criteria:
- Subjects who have received previous treatment with another Advanced Technology Medicinal Product (ATMP).
- Subjects with ECOG performance status of 3 or 4.
- Subjects deemed not suitable for surgery by the MDT.
- Uncontrolled diabetes, defined as HbA1c levels above 7.0 %.
- Any medical condition contraindicating the ability to tolerate general anaesthetic in the judgement of a consultant anaesthetist.
- Subjects who have a severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with trial participation or investigational product administration or in the judgment of the investigator, would make the subject inappropriate for entry into this trial.
- Subjects with clinically significant renal and liver impairment.
- Subjects undergoing an immunosuppression regimen or suffering from a primary immunodeficiency syndrome.
- Subjects with any known hypersensitivity to the culture and transport media compounds.
- Subjects with current or recurrent disease that could affect the administration, the action or disposition of the investigational product, or clinical or laboratory assessments.
- Subjects with clinically relevant or recent (within 2 years) history of substance abuse, including alcohol.
- Subject who has participated in any other interventional clinical trial within previous 30 days of the start of this study.
- Subjects with known presence of Human Immunodeficiency Virus (HIV) antibody, Hepatitis B surface antigen (HBsAg) or Hepatitis C antibody.
- Subject who, in the investigator's judgement, is unlikely to complete all protocol required study visits or procedures, including follow-up visits, or comply with the study requirements for participation
- Subjects with any medical condition, that in the investigator's judgement, is likely to interfere with assessment of safety or efficacy of study treatment.
- Subject who is pregnant.
- Subjects with cancer (except for controlled or controllable basal cell carcinoma).
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Treatment Arm
Arm Description
Patients will have a patch of expanded somatic mesenchymal stromal cells (MSCs) seeded onto a decellularised human tracheal-scaffold surgically implanted to repair bronchial fistula.
Outcomes
Primary Outcome Measures
Safety: Emergent or worsening Serious Adverse Events (SAEs) related to the BPF implant during the 3 months post-defect repair
Safety: Emergent or worsening Serious Adverse Events (SAEs) related to the BPF implant during the 3 months post-defect repair.
Efficacy: Bronchopleural Fistula (BPF) closure at 3 months assessed by visual appearance and no clinical signs of leaks.
Closure of BPF with no need for further surgical closure. Efficacy will be deemed demonstrated if 2 or more subjects meet the primary endpoint.
Secondary Outcome Measures
Change from Baseline in Physiological and Quality of Life scores at 3, 6, 9, 12 months, Evaluation Questionnaire 5D (EQ-5D), 6-minute walking test (6MWT), ambulatory oxygen (O2).
Impact as assessed in change from Baseline in Physiological and Quality of Life scores for each subject at 3, 6, 9, 12, 24 and up to 36 months post defect repair: QoL EQ-5D, 6-minute walking test, ambulatory O2 measurements.
Safety and tolerability: - Adverse Events (AEs) including pre-defined postoperative AEs of special interest up to 30± 3 days post implantation- Related AEs reported after 3, 6, 9, 12, 24 and 36 months
Adverse events related to the BPF implant procedures reported after 3, 6, 9, 12, 24 and 36 months.
Viability and the integrity of the repair area (closure) visually via bronchoscope. Integrity assessed by visual appearance of no visible leaks- Structural closure of the defect and visual health of the defect area and surrounding tissue
viability of the repair area and integration with vascular supply at 6, 9, 12, 24 and 36 months.
Absence of other surgical interventions at 6, 9, 12, 24 and 36 months
Interventions at the operative sites up to 6, 9, 12, 24 and 36 months
Full Information
NCT ID
NCT04435249
First Posted
May 29, 2020
Last Updated
November 21, 2022
Sponsor
Videregen Limited
Collaborators
Cell Therapy Catapult, Papworth Hospital NHS Foundation Trust, Royal Free Hospital NHS Foundation Trust
1. Study Identification
Unique Protocol Identification Number
NCT04435249
Brief Title
ENgineered Tissue Repair of BronchopleUral fiSTula
Acronym
ENTRUST
Official Title
Phase I/II, Open Label Study to Assess the Safety and Efficacy Autologous Bone Marrow-derived Mesenchymal Stromal Cells Seeded on to Decellularised Airway Scaffold in Subjects With Clinically Significant Bronchopleural Fistula
Study Type
Interventional
2. Study Status
Record Verification Date
November 2022
Overall Recruitment Status
Not yet recruiting
Study Start Date
October 2023 (Anticipated)
Primary Completion Date
March 2025 (Anticipated)
Study Completion Date
November 2027 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Videregen Limited
Collaborators
Cell Therapy Catapult, Papworth Hospital NHS Foundation Trust, Royal Free Hospital NHS Foundation Trust
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Phase I/II Open-label Study to Assess the Safety and Efficacy of a Novel Tissue Engineered Airway Product, Consisting of Expanded Autologous Bone Marrow (BM) Derived Mesenchymal Stromal Cells (MSC) Seeded on to a Decellularised Allogeneic Patch of an Airway Scaffold in Subjects With Clinically Significant Bronchopleural Fistula.
Detailed Description
The proposed clinical trial is a phase I/II open-label study to assess the safety and efficacy of a novel tissue engineered airway product, consisting of expanded autologous Bone Marrow (BM) derived Mesenchymal Stromal Cells (MSC) seeded on to a decellularised allogeneic patch of an airway scaffold in subjects with clinically significant bronchopleural fistula. It is a phase I/II open-label study, which is an uncontrolled pilot in 5 subjects.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bronchopleural Fistula
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
5 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Treatment Arm
Arm Type
Experimental
Arm Description
Patients will have a patch of expanded somatic mesenchymal stromal cells (MSCs) seeded onto a decellularised human tracheal-scaffold surgically implanted to repair bronchial fistula.
Intervention Type
Other
Intervention Name(s)
BPF-001
Intervention Description
Expanded somatic mesenchymal stromal cells (MSCs) seeded onto a decellularised human tracheal-scaffold
Primary Outcome Measure Information:
Title
Safety: Emergent or worsening Serious Adverse Events (SAEs) related to the BPF implant during the 3 months post-defect repair
Description
Safety: Emergent or worsening Serious Adverse Events (SAEs) related to the BPF implant during the 3 months post-defect repair.
Time Frame
3 months (90 days)
Title
Efficacy: Bronchopleural Fistula (BPF) closure at 3 months assessed by visual appearance and no clinical signs of leaks.
Description
Closure of BPF with no need for further surgical closure. Efficacy will be deemed demonstrated if 2 or more subjects meet the primary endpoint.
Time Frame
3 months (90 days)
Secondary Outcome Measure Information:
Title
Change from Baseline in Physiological and Quality of Life scores at 3, 6, 9, 12 months, Evaluation Questionnaire 5D (EQ-5D), 6-minute walking test (6MWT), ambulatory oxygen (O2).
Description
Impact as assessed in change from Baseline in Physiological and Quality of Life scores for each subject at 3, 6, 9, 12, 24 and up to 36 months post defect repair: QoL EQ-5D, 6-minute walking test, ambulatory O2 measurements.
Time Frame
36 months
Title
Safety and tolerability: - Adverse Events (AEs) including pre-defined postoperative AEs of special interest up to 30± 3 days post implantation- Related AEs reported after 3, 6, 9, 12, 24 and 36 months
Description
Adverse events related to the BPF implant procedures reported after 3, 6, 9, 12, 24 and 36 months.
Time Frame
36 months
Title
Viability and the integrity of the repair area (closure) visually via bronchoscope. Integrity assessed by visual appearance of no visible leaks- Structural closure of the defect and visual health of the defect area and surrounding tissue
Description
viability of the repair area and integration with vascular supply at 6, 9, 12, 24 and 36 months.
Time Frame
36 months
Title
Absence of other surgical interventions at 6, 9, 12, 24 and 36 months
Description
Interventions at the operative sites up to 6, 9, 12, 24 and 36 months
Time Frame
36 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
64 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male or female subjects 18 years or older.
Documented diagnoses of BPF through imaging and bronchoscopic examination.
BPF which involves the tracheobronchial junction or proximal bronchus.
Subjects who have failed primary repair.
Subjects who have no evidence of any primary or recurrent cancer (not limited to the surgical site) at the time of pre-operative screening as evidenced by CT and/or targeted biopsy (except for controlled or controllable basal cell carcinoma.
Subjects who have signed and dated written informed consent to participate in the study.
Females of childbearing potential (i.e. not surgically sterilised or post-menopausal for at least 2 years) must have a negative serum or urine pregnancy test.
Male and female subjects of childbearing potential (i.e. not surgically sterilised or post-menopausal for at least 2 years) must use forms of highly effective methods of contraception, which are defined as hormonal methods of contraception (oral, injection or implant), barrier methods (condom or occlusive cap (diaphragm or cervical/vault caps)) with spermicidal foam/gel/cream/film/suppository, or true abstinence for 1 month following surgery.
Subjects who have produced viable cells from Bone Marrow Aspirate.
Exclusion Criteria:
Subjects who have received previous treatment with another Advanced Technology Medicinal Product (ATMP).
Subjects with ECOG performance status of 3 or 4.
Subjects deemed not suitable for surgery by the MDT.
Uncontrolled diabetes, defined as HbA1c levels above 7.0 %.
Any medical condition contraindicating the ability to tolerate general anaesthetic in the judgement of a consultant anaesthetist.
Subjects who have a severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with trial participation or investigational product administration or in the judgment of the investigator, would make the subject inappropriate for entry into this trial.
Subjects with clinically significant renal and liver impairment.
Subjects undergoing an immunosuppression regimen or suffering from a primary immunodeficiency syndrome.
Subjects with any known hypersensitivity to the culture and transport media compounds.
Subjects with current or recurrent disease that could affect the administration, the action or disposition of the investigational product, or clinical or laboratory assessments.
Subjects with clinically relevant or recent (within 2 years) history of substance abuse, including alcohol.
Subject who has participated in any other interventional clinical trial within previous 30 days of the start of this study.
Subjects with known presence of Human Immunodeficiency Virus (HIV) antibody, Hepatitis B surface antigen (HBsAg) or Hepatitis C antibody.
Subject who, in the investigator's judgement, is unlikely to complete all protocol required study visits or procedures, including follow-up visits, or comply with the study requirements for participation
Subjects with any medical condition, that in the investigator's judgement, is likely to interfere with assessment of safety or efficacy of study treatment.
Subject who is pregnant.
Subjects with cancer (except for controlled or controllable basal cell carcinoma).
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Reg Affairs
Phone
+44203 728 9500
Email
regulatory@ct.catapult.org.uk
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing Plan Description
to follow
Learn more about this trial
ENgineered Tissue Repair of BronchopleUral fiSTula
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