Imaging FIB ONE in the Human Lung Using Endomicroscopy

NCT02604862 | Completed Early Phase 1 DMC

• 1 other identifier: FIB ONE
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief 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. 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).

Conditions

Fibrosis; Lung Cancer

Outcome Measures

Primary Outcomes (1)

• The measurement of FIB ONE fluorescence intensity in the lung (Part A).

  Quantify the change in fluorescence upon delivery of FIB ONE.

  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).

  Analysis to take one week to complete post procedure.

Study Arms (2)

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.

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

Other: FIB ONE; Other: AZD1236

Interventions

FIB ONE OTHER

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.

AZD1236 administration; FIB ONE administration

AZD1236 OTHER

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.

AZD1236 administration; FIB ONE administration

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Edinburgh: lead
• NHS Lothian: collaborator

Study Sites (1)

Royal Infirmary Edinburgh

Edinburgh, EH16 4TJ, United Kingdom

Location

MeSH Terms

Conditions

Fibrosis; Lung Neoplasms

Interventions

4-((5-chloro-2-pyridinyl)oxy)-1-((((4S)-4-methyl-2,5-dioxo-4-imidazolidinyl)methyl)sulfonyl)-piperidine

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Kev Dhaliwal, MBChB

  University of Edinburgh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 9, 2015
• First Posted: November 16, 2015
• Study Start: May 1, 2016
• Primary Completion: September 1, 2018
• Study Completion: September 1, 2018
• Last Updated: February 13, 2020

Record last verified: 2020-02

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)