FibrosisEarly Phase 1FIB ONENCT02604862
Imaging FIB ONE in the Human Lung Using Endomicroscopy
A Early Phase 1 study testing FIB ONE and AZD1236 in people with Fibrosis and Lung Cancer, run by University of Edinburgh at 1 site in United Kingdom.
Trial summary
While the process of fibrosis is essential for normal wound healing, an excessive and uncontrolled 'fibrotic' response can result in impaired tissue structure and function. In other words, affected 'fibrotic' tissues are unable to heal back to normal and therefore don't work as effectively as they normally would. Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- Fibrosis, Lung Cancer
- What is being tested?
- FIB ONE and AZD1236
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- May 2016to Sep 2018
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- All Cohorts Capacity to provide informed consent
- ≥ 16 years
- Attending consultant permission for bronchoscopy
- Thoracic CT scan taken within the previous 10 weeks
- Readily accessible target areas with bronchoscopy and FE
- Cohort 1 - Patients with a suspected or confirmed lung condition associated with increased activity of the fibroproliferative pathway and scheduled to undergo an elective bronchoscopy
- Cohort 2 - Patients undergoing planned cardiothoracic surgery for biopsy/resection of a lung condition associated with increased activity of the fibroproliferative pathway.
Who cannot join
- All Cohorts
- Refusal for participation by attending consultant
- Any history of anaphylaxis
- Significant coagulopathy or bleeding tendency, which causes bronchoscopy to be unsuitable, as determined by clinical co-investigator or the participant's attending consultant, using information which is routinely available
- Myocardial infarction in the preceding four weeks
- Women who are pregnant or are breastfeeding
- Receiving drugs that cause increased autofluorescence in the lung, specifically amiodorane and methotrexate
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Exploratory Clinical Study to Image the Intrapulmonary Microdosing of FIBroproliferation ONE (FIB ONE) Using Endomicroscopy
While the process of fibrosis is essential for normal wound healing, an excessive and uncontrolled 'fibrotic' response can result in impaired tissue structure and function. In other words, affected 'fibrotic' tissues are unable to heal back to normal and therefore don't work as effectively as they normally would.
In the case of the lung, fibrosis can occur across large parts of the lung such as in conditions like Idiopathic Pulmonary Fibrosis (IPF) and sarcoidosis or it can occur in much smaller patches such as around the borders of some lung tumours. At the moment the investigators don't fully understand the mechanisms of fibrosis and so therefore cannot monitor or treat these conditions as effectively as the investigators could. Despite the significant global financial burden of these diseases, treatment options are very limited and monitoring of disease progression remains a real challenge.
In an effort to address this problem, the research group are currently developing a library of novel optical molecular imaging SmartProbes that are targeted against key pathological processes in the human lung. The functional profile for this portfolio of probes is that they exhibit high stability and specificity in vivo and have a short activation time permitting rapid point-of-care in situ molecular profiling enabling in the future, improved diagnostic certainty and stratification for targeted pharmacological intervention. This clinical microdosing study protocol focuses around the intrapulmonary delivery of microdoses (<100µg) of the Smartprobe Fibroproliferation (FIB ONE) to disparate regions of the human lung to highlight MMP activity combined with an active MMP inhibitor (AZD1236) to the distal lung. This approach will enable the research team to directly demonstrate the utility of this SmartProbe-based platform in the validation of drug target engagement in areas of suspected fibroproliferation (characterised by increased MMP activity).
Read the detailed description
The primary endpoint is to visualise the delivery of a microdose of FIB ONE and assess imaging parameters in patients with lung conditions using two microendoscopy systems (Part A). A secondary objective is to quantify the change in mean FIB ONE fluorescence amplification gradient in the presence of AZD1236 in the fibroproliferative lung (Part B). Imaging will be performed using a novel multi-colour widefield fluorescence microendoscopy platform and a commercially available imaging platform.
Cohort 1 will consist of 20 patients scheduled for routine elective diagnostic or surveillance bronchoscopy with a fibroproliferative lung condition and Cohort 2 will consist of 6 patients undergoing planned cardiothoracic surgery for biopsy/resection of lung conditions characterised by excessive activity of the fibroproliferative pathway. For both cohorts, eligibility will be verified by a clinical trial physician after written informed consent has been obtained.
For cohort 1, a bronchoscopy with lavage will be performed to harvest broncho-alveolar lavage fluid (BALF). For cohort 2, a sample of resected lung tissue will be analysed. Fibre-based endomicroscopy (FE) will be performed and up to 100μg of FIB ONE and PBS/AZD1236 will be instilled. CT identified regions of architecturally normal lung in all participants will act as internal controls and will be used to compare MMP activity in normal and diseased lung tissue.
Participants will be asked to provide routine blood samples before and after FIB ONE and AZD1236 administration. A cardiorespiratory exam and routine observations will be performed 4-6 hours following administration and all participants will be assessed for discharge. All participants will either be contacted by a member of the research team via telephone or ward visit 24 hours (± 4 hours) after dosing to ensure no AEs/SAEs were experienced. The participant's involvement in the study is concluded when the 24 hour assessment has been successfully completed and all AEs/SAEs have been resolved.
- Conditions
- Fibrosis, Lung Cancer
- Being tested
- FIB ONE, AZD1236
- Medical subject headings
- Fibrosis, Lung Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FIB ONEOther
FIB ONE will be administered to each patient during a bronchoscopy procedure. Fibre-based endomicroscopy and two types of viewer software will be used to detect FIB ONE signal in the lung.
AZD1236Other
AZD1236 will be delivered at microdose concentrations and is thus considered to be unable to exert any pharmacologic effect outside the area of administration and unlikely to cause an adverse reaction.
| Study group | Role | What they receive |
|---|---|---|
| FIB ONE administration | Experimental | All participants in this clinical study will be dosed on one occasion with FIB ONE. The final dosage will be less than 100 µg. Receives: Other: FIB ONE; Other: AZD1236 |
| AZD1236 administration | Experimental | To quantify the change in mean FIB ONE fluorescence amplification gradient in the presence of AZD1236 in the fibroproliferative lung Receives: Other: FIB ONE; Other: AZD1236 |
What is being measured
The primary outcome is the main question the study is designed to answer.
The measurement of FIB ONE fluorescence intensity in the lung (Part A).
Quantify the change in fluorescence upon delivery of FIB ONE.
Measured: Analysis to take one week to complete post procedure.
Secondary outcomes (1)
The measurement of FIB ONE fluorescence intensity in the lung in the presence of PBS or AZD1236 (Part B).
Quantify the change in fluorescence upon delivery of FIB ONE and AZD1236/PBS.
Measured: Analysis to take one week to complete post procedure.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Nov 2015 (estimated)
- Study startMay 2016
- Primary completionSep 2018
- Study completionSep 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for FibrosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Edinburgh
- Sponsor type
- University, hospital or other
- Collaborators
- NHS Lothian
- Responsible party
- Sponsor
- Investigators
- Kev Dhaliwal, MBChB, Principal investigator, University of Edinburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02604862
- Sponsor's protocol ID
- FIB ONE
- Acronym
- FIB ONE
- Status last verified
- Feb 2020
- First submitted
- 9 Nov 2015
- Last updated
- 13 Feb 2020
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Exploratory Clinical Study to Image the Intrapulmonary Microdosing of FIBroproliferation ONE (FIB ONE) Using Endomicroscopy
- ClinicalTrials.gov ID
- NCT02604862
- Acronym / sponsor ID
- FIB ONE / FIB ONE
- Conditions
- Fibrosis, Lung Cancer
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- University of EdinburghUniversity, hospital or other
- Collaborators
- NHS Lothian
- Study start
- May 2016 (actual)
- Primary completion
- Sep 2018 (actual)
- Study completion
- Sep 2018 (actual)
- First posted
- 16 Nov 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
While the process of fibrosis is essential for normal wound healing, an excessive and uncontrolled 'fibrotic' response can result in impaired tissue structure and function. In other words, affected 'fibrotic' tissues are unable to heal back to normal and therefore don't work as effectively as they normally would.
In the case of the lung, fibrosis can occur across large parts of the lung such as in conditions like Idiopathic Pulmonary Fibrosis (IPF) and sarcoidosis or it can occur in much smaller patches such as around the borders of some lung tumours. At the moment the investigators don't fully understand the mechanisms of fibrosis and so therefore cannot monitor or treat these conditions as effectively as the investigators could. Despite the significant global financial burden of these diseases, treatment options are very limited and monitoring of disease progression remains a real challenge.
In an effort to address this problem, the research group are currently developing a library of novel optical molecular imaging SmartProbes that are targeted against key pathological processes in the human lung. The functional profile for this portfolio of probes is that they exhibit high stability and specificity in vivo and have a short activation time permitting rapid point-of-care in situ molecular profiling enabling in the future, improved diagnostic certainty and stratification for targeted pharmacological intervention. This clinical microdosing study protocol focuses around the intrapulmonary delivery of microdoses (<100µg) of the Smartprobe Fibroproliferation (FIB ONE) to disparate regions of the human lung to highlight MMP activity combined with an active MMP inhibitor (AZD1236) to the distal lung. This approach will enable the research team to directly demonstrate the utility of this SmartProbe-based platform in the validation of drug target engagement in areas of suspected fibroproliferation (characterised by increased MMP activity).
Detailed description
The primary endpoint is to visualise the delivery of a microdose of FIB ONE and assess imaging parameters in patients with lung conditions using two microendoscopy systems (Part A). A secondary objective is to quantify the change in mean FIB ONE fluorescence amplification gradient in the presence of AZD1236 in the fibroproliferative lung (Part B). Imaging will be performed using a novel multi-colour widefield fluorescence microendoscopy platform and a commercially available imaging platform.
Cohort 1 will consist of 20 patients scheduled for routine elective diagnostic or surveillance bronchoscopy with a fibroproliferative lung condition and Cohort 2 will consist of 6 patients undergoing planned cardiothoracic surgery for biopsy/resection of lung conditions characterised by excessive activity of the fibroproliferative pathway. For both cohorts, eligibility will be verified by a clinical trial physician after written informed consent has been obtained.
For cohort 1, a bronchoscopy with lavage will be performed to harvest broncho-alveolar lavage fluid (BALF). For cohort 2, a sample of resected lung tissue will be analysed. Fibre-based endomicroscopy (FE) will be performed and up to 100μg of FIB ONE and PBS/AZD1236 will be instilled. CT identified regions of architecturally normal lung in all participants will act as internal controls and will be used to compare MMP activity in normal and diseased lung tissue.
Participants will be asked to provide routine blood samples before and after FIB ONE and AZD1236 administration. A cardiorespiratory exam and routine observations will be performed 4-6 hours following administration and all participants will be assessed for discharge. All participants will either be contacted by a member of the research team via telephone or ward visit 24 hours (± 4 hours) after dosing to ensure no AEs/SAEs were experienced. The participant's involvement in the study is concluded when the 24 hour assessment has been successfully completed and all AEs/SAEs have been resolved.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| FIB ONE administration | Experimental | Other: FIB ONE, Other: AZD1236All participants in this clinical study will be dosed on one occasion with FIB ONE. The final dosage will be less than 100 µg. |
| AZD1236 administration | Experimental | Other: FIB ONE, Other: AZD1236To quantify the change in mean FIB ONE fluorescence amplification gradient in the presence of AZD1236 in the fibroproliferative lung |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- All Cohorts Capacity to provide informed consent
- ≥ 16 years
- Attending consultant permission for bronchoscopy
- Thoracic CT scan taken within the previous 10 weeks
- Readily accessible target areas with bronchoscopy and FE
Key exclusion criteria (7 listed)
- All Cohorts
- Refusal for participation by attending consultant
- Any history of anaphylaxis
- Significant coagulopathy or bleeding tendency, which causes bronchoscopy to be unsuitable, as determined by clinical co-investigator or the participant's attending consultant, using information which is routinely available
- Myocardial infarction in the preceding four weeks
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FIB ONEFIB ONE will be administered to each patient during a bronchoscopy procedure. Fibre-based endomicroscopy and two types of viewer software will be used to detect FIB ONE signal in the lung. | Other | AZD1236 administration, FIB ONE administration |
| AZD1236AZD1236 will be delivered at microdose concentrations and is thus considered to be unable to exert any pharmacologic effect outside the area of administration and unlikely to cause an adverse reaction. | Other | AZD1236 administration, FIB ONE administration |
Primary outcome
The measurement of FIB ONE fluorescence intensity in the lung (Part A).
Time frame: Analysis to take one week to complete post procedure.
Quantify the change in fluorescence upon delivery of FIB ONE.
1 secondary outcome
The measurement of FIB ONE fluorescence intensity in the lung in the presence of PBS or AZD1236 (Part B).
Time frame: Analysis to take one week to complete post procedure.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Feb 2020.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kev Dhaliwal, MBChB principal investigator
University of Edinburgh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing FIB ONE and AZD1236 in people with Fibrosis and Lung Cancer, run by University of Edinburgh at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The measurement of FIB ONE fluorescence intensity in the lung (Part A). (time frame: Analysis to take one week to complete post procedure.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Feb 2020.