Development of Airway Absorption Sampling Methods for Biomarker Assessment in Probable Idiopathic Pulmonary Fibrosis (IPF) Patients
Conditions: Idiopathic Pulmonary Fibrosis, Sarcoidosis
Sponsor: Imperial College London

 
 
 
 
 
Study Protocol: FIBRO-SAM, IRAS Project Number: 239911 
 
Version 3.3 
 
 
 
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Date: 08.06. 2020 
 
Study Protocol 
 
Short Title: FIBRO-SAM 
 
Full Title:  
 
Development of Airway Absorption Sampling Methods for Biomarker 
Assessment in Probable Idiopathic Pulmonary Fibrosis (IPF) Patients 
 
IRAS project Number  
 
 239911 
  
CHIEF INVESTIGATOR:   
 
                    Dr Melissa Wickremasinghe 
 
PRINCIPAL INVESTIGATORS: 
  
                       Prof Onn Min Kon, Prof Trevor Hansel  
 
CO-INVESTIGATORS:  
 
 St Mary’s Hospital (Paddington, London, UK): 
  
                          Dr Mirae Park, Dr Ryan Thwaites, Nelisa Poshai,  
                          Dr Nehmat Singh, Dr Romana Kuchai, Dr Anne-Marie Russell 
 
 Genentech (South San Francisco, California, USA):  
 
                           Dr Rebecca Sheng, Dr Maggie Neighbors 
 
MAIN SPONSOR:  
 
                           Imperial College London 
 
FUNDER:  
 
                            Genentech, South San Francisco, California, USA 
  
 
 

 
 
 
 
 
Study Protocol: FIBRO-SAM, IRAS Project Number: 239911 
 
Version 3.3 
 
 
 
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Date: 08.06. 2020 
 
 
 
STUDY CENTRE:  
 
 
Patients 
Healthy volunteers 
The Bronchoscopy Suite 
Queen 
Elizabeth 
Queen 
Mother 
(QEQM) Building 
Imperial College Healthcare NHS Trust 
St Mary’s Hospital, Second Floor 
Paddington 
London W2 1NY 
Imperial Clinical Respiratory Research Unit 
(ICRRU) 
Imperial College Healthcare NHS Trust 
St Mary’s Hospital, Mint Wing, First Floor 
Paddington 
London, W2 1NY 
 
 
 
REC reference: 20/LO/0176  
 
 
 
 
Protocol authorised by: 
(Name) 
 
Role 
Date 
Signature 
 
 
 
 
 
 
 
 
 
 
 
Study Coordination Centre:  
 
For general queries, supply of study documentation, and collection of data, please contact: 
 
Study coordinator:  Ms Nelisa Poshai 
 
Address: 
 
ICCRU, Mint Wing, St Mary’s Hospital, Paddington London W2 1NY 
 
E-mail: nelisa.poshai@nhs.net 
Phone: 02033125734 
 
 

 
 
 
 
 
Study Protocol: FIBRO-SAM, IRAS Project Number: 239911 
 
Version 3.3 
 
 
 
Page 3 of 19 
Date: 08.06. 2020 
 
Clinical Queries 
Clinical queries should be directed to:  
 
Dr Melissa Wickremasinghe, Prof Onn Min Kon and Prof Trevor T. Hansel. 
 
Sponsor 
 
Imperial College London is the main research Sponsor for this study. For further information 
regarding the sponsorship conditions, please contact the Head of Research Governance and 
Integrity at: 
 
 
 
Joint Research Compliance Office 
Imperial College London and Imperial College Healthcare NHS 
Trust 
2nd Floor, Medical School 
Norfolk Place 
London, W2 1PG 
 
Tel: 0207 594 1872 
 
Every care was taken in writing this protocol and this has been reviewed by the co-
investigators. Problems relating to this study should be referred, in the first instance, to the 
Chief Investigator.  
 
This study will adhere to the principles outlined in the ICH-GCP Guideline originating from 
the Declaration of Helsinki, 1964 and all amendments, as well as the NHS Research 
Governance Framework for Health and Social Care. It will be conducted in compliance with 
the protocol, the General Data Protection Regulation (GDPR) 2018 and other regulatory 
requirements as appropriate.  
 
 

 
 
 
 
 
Study Protocol: FIBRO-SAM, IRAS Project Number: 239911 
 
Version 3.3 
 
 
 
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Date: 08.06. 2020 
GLOSSARY OF ABBREVIATIONS 
AE 
adverse events 
BAL 
bronchoalveolar lavage 
BS 
bronchosorption 
CCL 
chemokine of cysteine-cysteine type 
CRF 
case report form 
CXC 
chemokine of cysteine -X- cysteine type 
C3M 
collagen degradation markers 
CRPM 
c-reactive protein degraded by MMP 
 
DLco 
diffusion factor for carbon monoxide 
EL-M7 
MMP-7 generated elastin fragments 
FEV1/FVC 
forced expiratory volume/forced vital capacity 
GDPR 
General Data Protection Regulation  
KL-6 
Krebs von den Lungen 6  
IgE 
immunoglobulin E 
IL 
interleukin 
IPF 
interstitial pulmonary fibrosis 
MDT 
multi-disciplinary team 
MLF 
mucosal lining fluid 
MMP 
matrix metalloprotease 
MSD 
Meso Scale Discovery 
NAC 
nasal allergen challenge 
NS 
nasosorption 
SAE 
serious adverse event 
SAM 
synthetic absorptive matrix 
SP 
surfactant protein 
sRAGE 
soluble receptor for advanced glycation end products 
 
KEYWORDS 
 
 
Idiopathic 
pulmonary 
fibrosis, 
biomarkers, 
mucosal 
lining 
fluid, 
nasosorption, 
bronchosorption, cytokines, chemokines,  
 
 
 
 
 
 
 

 
 
 
 
 
Study Protocol: FIBRO-SAM, IRAS Project Number: 239911 
 
Version 3.3 
 
 
 
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Date: 08.06. 2020 
 
STUDY SUMMARY 
 
TITLE 
FIBRO-SAM: Development of Airway Absorption Sampling Methods 
for Biomarker Assessment in Probable Idiopathic Pulmonary Fibrosis 
(IPF) Patients 
 
DESIGN 
Observational study with opportunistic airway sampling in patients 
with probable Idiopathic Pulmonary Fibrosis and Sarcoidosis, who 
are undergoing bronchoscopy as part of their diagnosis and/or 
monitoring 
 
AIMS 
To assess molecules reflecting pulmonary fibrosis using novel upper 
and lower airway sampling methods of absorption; nasosorption,  
(upper airway) and bronchosorption (lower airway). 
OUTCOME 
MEASURES 
Comparing levels of mediators including periostin, surfactant protein 
D (SPD), CCL18, CXCL13 in blood, nasal and bronchial airway 
mucosal lining fluid. 
 
POPULATION 
Probable Idiopathic Pulmonary Fibrosis patients (IPF) undergoing 
bronchoscopy, n = 30 
Sarcoidosis patients, n = 15 
Healthy volunteers, n = 15 
 
ELIGIBILITY 
Adults (aged 40 to 85 years) will need to meet inclusion and 
exclusion criteria. Patients in this study will be selected at the time of 
their scheduled clinical bronchoscopy at St Mary’s Hospital at 
Imperial College Healthcare Trust and all Healthy controls will be 
recruited by approaching carers and partners of recruited patients as 
well as advertising in hospital OPA, public places and local media  
DURATION 
Clinical Phase: March 2020 to March 2021 (estimated) 

 
 
 
 
 
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Contents 
1 
INTRODUCTION ......................................................................................................................... 8 
Synthetic absorptive matrix (SAM): .............................................................................................. 9 
Nasosorption after nasal allergen challenge ............................................................................... 9 
Bronchosorption: .............................................................................................................................. 9 
2 
STUDY SUMMARY .................................................................................................................. 10 
3 
STUDY OBJECTIVE ................................................................................................................. 12 
3.1 
Research Question and Hypotheses ............................................................................... 12 
3.2 
Primary Outcome ................................................................................................................ 12 
3.3 
Secondary Outcomes ........................................................................................................ 12 
4 
STUDY DESIGN AND SAMPLE COLLECTION .................................................................. 13 
5 
ENTRY CRITERIA .................................................................................................................... 14 
5.1 
Inclusion Criteria ................................................................................................................. 14 
5.2 
Exclusion Criteria ................................................................................................................ 15 
5.3 
Withdrawal Criteria ............................................................................................................. 17 
6 
ADVERSE  EVENTS ................................................................ Error! Bookmark not defined. 
6.1 
Definitions ............................................................................................................................ 17 
6.2 
Reporting Procedures ........................................................................................................ 17 
6.2.1 
Non Serious AES ........................................................................................................ 17 
6.2.2 
Serious AES ................................................................................................................. 18 
7 
ASSESSMENT AND FOLLOW-UP  ....................................................................................... 18 
7.1 
Visits and study procedures for Probable IPF and Sarcoidosis patients ................... 18 
7.1.1 
Schedule of assessments for Probable IPF and Sarcoidosis patients ............... 20 

 
 
 
 
 
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7.2 
Visits and study procedures for healthy volunteers ...................................................... 21 
7.2.1 
Schedule of assessments for healthy volunteers ................................................... 22 
8 
SAMPLE COLLECTION AND PREPARATION PROCEDURES ...................................... 22 
8.1 
Serum ................................................................................................................................... 22 
8.2 
Whole Blood ........................................................................................................................ 23 
8.2.1 
Whole blood for DNA .................................................................................................. 23 
8.2.2 
Whole blood for RNA .................................................................................................. 23 
8.3 
Airway SAM samples ......................................................................................................... 23 
8.4 
BAL samples ....................................................................................................................... 24 
8.5 
Urine Sample ....................................................................................................................... 24 
8.6 
Sample Storage and Destruction ..................................... Error! Bookmark not defined. 
8.7 
Laboratory Procedures, Storage and Shipment ............................................................ 24 
9 
STATISTICS AND DATA ANALYSIS .................................................................................... 24 
10 
REGULATORY ISSUES ....................................................................................................... 26 
10.1 
Ethics Approval ............................................................... Error! Bookmark not defined. 
10.1.1 
Ethical/Regulatory Considerations ........................ Error! Bookmark not defined. 
10.2 
Consent ............................................................................ Error! Bookmark not defined. 
10.3 
Confidentiality .................................................................................................................. 26 
10.4 
Indemnity .......................................................................................................................... 26 
10.5 
Sponsor ............................................................................................................................ 26 
10.6 
Funding ............................................................................................................................. 26 
10.7 
Audits ................................................................................................................................ 27 
11 
STUDY MANAGEMENT ....................................................................................................... 27 
11.1 
Sample Shipment ............................................................................................................ 27 

 
 
 
 
 
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12 
PUBLICATION POLICY ........................................................................................................ 27 
 
1 INTRODUCTION  
Idiopathic Pulmonary Fibrosis (IPF) is a progressive and incapacitating lung disorder that has 
a variable clinical course, but is generally fatal within a few years (1, 2). The diagnosis of IPF 
is based on clinical features, lung function tests showing interstitial disease (decreased 
transfer of carbon monoxide) and usual interstitial pneumonia (UIP) on high resolution 
computerised tomography (HRCT) scan of the lung fields (3, 4). As part of their diagnostic 
work up, most patients with probable IPF require bronchoscopy for taking broncho-alveolar 
lavage (BAL) samples. 
Therapy for IPF is gradually being developed with drugs such as pirfenidone (5) and 
nintedanib (6) showing modest effects. However, the variable and pleiotropic nature of IPF 
suggests that combination and personalised therapy will be required (7). In recent years, 
there have been extensive efforts to measure blood biomarkers in this disease, and a number 
of blood biomarkers have been described in IPF:  
 MMP-7, ICAM-1, VCAM-1, CXCL8/IL-8, S100A12 (8) 
 surfactant proteins (SP)-A & D (9, 10) 
 periostins (11) 
 KL6 (12) 
 antibodies to heat shock protein (HSP) 70 (13) 
 soluble receptor for advanced glycation end products (sRAGE) (14)  
 CCL18 (15), CXCL13 (16) 
 collagen biomarkers and protease degradation products (collagen neo-epitopes) (17)  
 CA19-9 and CA125 
 
Very recently a 52 gene expression profile in blood has been found to be predictive of 
outcome in IPF (18). 
 
In IPF there is an urgent need to develop new methods for taking lung samples from a 
bronchoscope to measure mucosal inflammation. Inflammatory mediators in the mucosal 
lining fluid (MLF) reflect underlying inflammation, but existing bronchoscopic methods (BAL 
and biopsy) have significant drawbacks. 
 
Bronchosorption involves passing a special medical sampling device down the operating 
portal of the bronchoscope. Using bronchosorption to obtain samples and identify molecular 
signatures of respiratory disease, we hope to achieve new fundamental insights and refine 
the investigation, diagnosis, stratification and monitoring of IPF. We can discover biomarkers 
to help assess the effects of existing therapies and identify potential targets for novel 
treatments. 
 
In addition to BAL samples being taken from the bronchoscope for clinical diagnostic 
purposes, in this study we shall perform upper airway sampling (nasosorption) and this will 
be compared with the lower airway sampling of bronchosorption.  

 
 
 
 
 
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This study is being carried out for clinical research purposes, is optional for patients, and is 
unlikely to benefit the patient personally. This study is unlikely to change the clinical diagnosis 
of a patient and will not change their drug treatment.  
 
Absorption of Airway Mucosal Lining Fluid with Synthetic Absorptive Matrix (SAM) 
 
Synthetic absorptive matrix (SAM)  
 
SAM  strips are like blotting paper and are now widely used to obtain nasal MLF by 
nasosorption having first been used in 2003 (19, 20).  These absorbent materials are 
comfortable to use and can obtain MLF even from inflamed noses at frequent intervals over 
extended periods of time. There is minimal protein binding to the SAM strip, and proteins in 
the fluid can be efficiently eluted. 
 
Nasosorption  
 
After a nasal allergen challenge, we have used the technique of nasosorption to absorb 
mucosal lining fluid from the nose at frequent intervals. Nasosorption uses a small strip of 
absorbent material on a handle to soak up fluid from the inside surface of the nostril. 
Nasosorption is a CE marked device that uses medical grade materials and is produced in a 
specialised medical device manufacturing company. This is placed inside the nostril and left 
for 60 seconds, keeping light pressure with a finger to absorb fluid before being removed. 
This technique is very gentle and minimises rubbing and brushing inside the nostril. The 
material absorbs the fluid and chemicals produced by the nasal cells that can then be 
extracted and measured.  After nasal allergen challenge (NAC) the eluate from nasosorption 
contains inflammatory mediators, cytokines and chemokines at high detectable levels, and 
this has been shown after NAC with grass pollen (21, 22), cat allergen (23) and 
lipopolysaccharide (24). A recent manuscript has described full gene expression changes 
after NAC with grass pollen (25) In addition, following experimental human rhinovirus (HRV) 
challenge in asthma patients, nasosorption and bronchosorption were performed to measure 
IL-15 (26), IL-25 (27), IL-33 (28) and IL-18 (29). A very complete profile of cytokines and 
chemokines following HRV challenge in asthma has recently been reported (30)  (31), and 
viral load and cytokines have been measured after RSV bronchiolitis of infancy (32). An 
extensive validation study has been carried out comparing performance of nasosorption with 
nasal lavage (33). 
 
Bronchosorption: 
 
The Respiratory Medicine group in Imperial College have developed a bronchosorption device 
that employs a different proprietary medical grade soft fibrous SAM at the tip. The 
bronchosoprtion device is now CE-marked and has been used in over 1500 patients and healthy 
volunteers. Bronchosorption  has the advantage of being less invasive and causing less dilution 
than a broncholveolar lavage (BAL). A straw of SAM or synthetic sponge is attached to a leading 
plastic wire, and placed down a sheath within the operating portal of a bronchoscope. Under 
direct bronchoscopic vision the SAM is advanced against the mucosa of a main bronchus or 
segmental bronchus for up to 30 secs, under direct vision the SAM is then withdrawn up the 
sheath, and MLF eluted from the detached SAM. The eluted MLF may then be analysed for 

 
 
 
 
 
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Page 10 of 30      
levels of inflammatory mediators: such as a panel of chemokines and cytokines using the MSD 
analyser. High detectable levels of mediators of inflammation can then be measured in the 
bronchial MLF. Prof Onn Min Kon of the Department of Respiratory Medicine at Saint Mary’s 
Hospital has an extensive experience of succesfully sampling over 1000 patients to collect over 
1000 bronchosorption samples. The procedure is well tolerated and up to 40l of fluid is 
absorbed on a single occasion. The bronchosorption kit is supplied in sterile packs, and has 
undergone durability and functional testing, and is supplied steriled by gamma irradiation.  In 
the HRV infection model in patients with allergic asthma and healthy controls, both nasosorption 
and bronchosorption have been carried out to measure IL-15 (26), IL-25 (27), IL-33 (28) and IL-
18 (29). Bronchosoorption has been shown to have considerable promise for measuring 
biomarkers in asthma, and has potential to be used for personalised medicine and selection of 
specific biologics  (30)  (31).  
 
 
Figure 1: Bronchosorption device 
Bronchoalveolar Lavage (BAL): 
 
As part of the bronchoscopy procedure, the doctor intends to collect a BAL sample. This is 
done by instilling some sterile fluid into the lung and then drawing this fluid back out again 
with the bronchoscope. The BAL fluid is then studied to help in the diagnosis of lung diseases. 
For our study, we will collect this fluid for research purposes. 
 
2 STUDY SUMMARY 
In patients are having bronchscopy with BAL sampling done for their diagnostic work up, we 
propose bronchosorption samples be also taken during bronchoscopy for patients with probable 
IPF (n=30) and sarcoidosis (n=15) who agree to take part in this study.. For our clinical research 
we shall collect BAL and the following additional samples at the bronchoscopy baseline visit: 
serum, whole blood, and mucosal lining fluid by absorption: nasosorption, bronchosoprtion and 

 
 
 
 
 
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Page 11 of 30      
urine. We will also be collecting serum, whole blood, and nasosorption samples at 3 and 6 
month follow-up visits.  
 
In addition we shall study age matched healthy volunteers (n=15) who will not undergo 
bronchoscopy.From these participants  we will collect serum, whole blood, and nasosorption 
only. Healthy volunteers are included in this study since we need to compare the levels of 
biomarkers in blood and nasal mucosal lining fluids in patients with probable idiopathic 
pulmonary fibrosis (IPF) and sarcoidosis with healthy volunteers  
 
We will measure a range of molecules and mediators in the samples collected.  We can 
assess molecules reflecting pulmonary fibrosis in the lungs (BAL), and using novel sampling 
methods of bronchial mucosal lining fluid (bronchosorption), and also from the upper airway 
(nasosorption). A critical issue is whether disease in the alveoli and the very small bronchioles 
will permit molecules to be transmitted by the mucociliary escalator (MCE) up to the larger 
airways. 
 
Biomarkers in the airways will reflect distal pulmonary fibrosis immunopathology. IPF and 
sarcoidosis are diseases of fibrosis and granuloma formation and will have different 
associated biomarkers.  
 
Airway absorption sampling methods and biomarkers can be used to understand molecular 
mechanisms, diagnose and monitor pulmonary fibrosis. The biomarkers can contribute to 
personalised medicine through the selection and stratification of patients for specific therapy, 
to monitor that therapy, and to provide targets for new therapy. 
 
The total study involves a total of 30 subjects with probable IPF, 15 patients with sarcoidosis 
and 15 healthy volunteers. Recruitment for this study is likely to take between 12 and 24 
months. An interim analysis at 12 months will be able to identify any emerging differences in 
biomarkers between the groups, and allow the nature of biomarkers of inflammation to be 
adjusted prior to the final analyses. In an exploratory study of novel methods of mucosal 
sampling in probable IPF and sarcoidosis, we do not know the rate of recruitment, and would 
prefer not to specify an exact number of patients for when interim analysis is performed. 
 
 
Biomarkers to be measured: 
1. Blood (serum) and MLF 
 
There will be a particular focus on 4 biomarkers: 
Periostin, surfactant protein D (SPD), CCL18 and CXCL13 
 
A range of other biomarkers will be measured including the following: 
 
 IL-1β, IL-2, IL-8 (CXCL8), IL-12, IL-13, IL-17, IL-23, IL-33 
 TGF-β, FGF basic, TNF-β, CTGF 
 sICAM-1, sVCAM-1, CRP, SAA 
 D-dimer and C3a, C5 

 
 
 
 
 
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Other biomarkers of inflammation may also be measured. 
 
2. Whole blood for gene expression (mRNA) and DNA sequencing: 
 
 To examine in peripheral blood expression of genes and or gene signatures related 
to IPF and disease progression 
 To examine genetic loci that contribute to IPF risk and disease progression such 
as muc5b and TERT 
  
3. Urine 
 
 Collagen fragments and bioactive lipids involved in inflammation, which may include, 
but are not limited to C3M, pro-C3, CRPM, and EL-M7, may be measured. 
 
 
 
3 STUDY OBJECTIVE 
 
3.1 Research Question and Hypotheses 
1. Are levels of periostin, surfactant protein D (SPD), CCL18, CXCL13 and other 
biomarkers in bronchial mucosal lining fluid (MLF) useful as a biomarker for IPF 
patients? 
2. Do levels of mediators in less invasive upper airway samples (nasosorption) correlate 
with levels in lower airway samples (bronchosorption)? 
3. Do airway levels of these mediators add value when used in conjunction with blood 
biomarkers of IPF? 
3.2 Primary Outcome 
Comparison of bronchial lining fluid levels of biomarkers/mediators (periostin, surfactant 
protein D (SPD), CCL18, CXCL13) in patients with IPF and sarcoidosis.  
 Determination of level of significance in the levels of the bronchial mediators 
between IPF and sarcoidosis patients. 
3.3 Secondary Outcomes 
1. Comparing 
mediator 
levels 
between 
airway 
samples 
(nasosorption 
and, 
bronchosorption) within and across the 3 groups (probable IPF, sarcoidosis and 
healthy controls). Establish significance between groups and correlations across 
patient groups for sampling types. 
2. Comparing mediator levels and mRNA (gene expression) in blood with airway 
mediator levels across the 3 patient groups, and assessing the degree of correlation. 

 
 
 
 
 
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Page 13 of 30      
 
3. Comparing mediator levels in airway samples and blood with clinical parameters 
4. Comparing urine metabolites across the 3 patient groups. 
4 STUDY DESIGN AND SAMPLE COLLECTION 
Any patients with probable IPF and sarcoidosis, who will be having bronchoscopy as part of 
their clinical diagnostic work up will be invited to have extra samples taken, including by the 
method of bronchosorption. However, the bronchosorption analysis results are not likely to 
benefit the individual subject. 
 
Patients and healthy volunteers 
 
Potential participants with probable IPF and Sarcoidosis having bronchoscopy as part of their 
clinical diagnostic work up will be identified by the study doctors and the Multi-Disciplinary 
Team (MDT) on the basis of inclusion/exclusion criteria. Patients who meet the inclusion and 
exclusion criteria will then be invited to participate in the study. Health controls will be 
recruited by approaching carers and partners of recruited patients as well as advertising in 
clinics, public places as well as local media.  
4.1 Consent 
Consent to enter the study will be sought after the patient has read and understood and had 
time to discuss the information contained within the Participant Information Sheet with friends 
and family. Signed participant consent will be obtained. The right of the participant to refuse 
to participate without giving reasons will be respected.  
 
After the participant has entered the study the clinician remains free to give alternative 
treatment to that specified in the protocol at any stage if he/she feels it is in the participant’s 
best interests, and the reasons for doing so should be fully documented. In such cases the 
participants remain in the study for the purposes of follow-up. All participants are free to 
withdraw at any time from the study without giving reasons and without prejudicing further 
treatment and care. 
 
4.2 Patient Population 
Patients diagnosed with probable IPF and Sarcoidosis will be included. Patients with probable 
IPF and Sarcoidosis will be selected from clinic lists for patients undergoing bronchoscopy 
as part of their clinical assessment, and they will be invited to participate in this study that 
involves additional sampling for clinical research purposes. 
Probable IPF patients must have Usual Interstitial Pneumonitis (UIP) on CT scan and will be 
sub classified by gas transfer (DLco corrected for haemoglobin as detailed below; 
o Mild (DLco>60) 

 
 
 
 
 
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o Moderate (DLco 40-60) 
o Severe (DLco<40) 
 
Healthy volunteers (age/sex matched, non-smoking, without a clinical history of atopy). 
 
The patient populations will include: 
 Probable Idiopathic Pulmonary Fibrosis (IPF), n=30   
 Sarcoidosis patients, n=15 
 Healthy Volunteers n=15  
 
4.3 Sampling 
For patients diagnosed with probable IPF and Sarcoidosis, BAL will be collected on the day 
of their scheduled bronchoscopy. Blood, nasosorption (NS), and bronchosorption (BS) 
samples will also be collected.  Furthermore, on the day of their optional 3 and 6 months 
follow up visits, we shall collect blood and nasosorption (NS) samples. It is important to 
stress that bronchosorption samples must be taken before BAL or bronchial biopsy 
samples. All patients will have had HRCT of the lung and lung function testing (spirometry 
and DLco) up to 3 months before bronchoscopy sampling. Healthy volunteers will have a 
single visit with blood and NS sampling - but no bronchial samples. 
With regard to possible coronavirus (COVID-19) infection, this clinical research project will 
meet Policies and Procedures in conjunction with the NHS, Imperial College London and 
Public Health England (PHE) guidelines. This will include use of Personal Protective 
Equipment (PPE) with appropriate clinical facilities and procedures. Appropriate precautions 
will be taken with sample collection, handling and processing. 
 
5 ENTRY CRITERIA 
 
5.1 Inclusion Criteria for Probable Idiopathic Pulmonary Fibrosis (IPF) 
 
- 
Adult male or female patients aged 40 to 85 years  
- 
Women of childbearing age should not be pregnant, planning to get pregnant or 
breast-feeding.  
- 
Command of the English language to be able to give informed consent. 
- 
Probable IPF requiring bronchoscopy to confirm the diagnosis, agreed within the 
local multi-disciplinary team (MDT).,according to the American Thoracic 
Society/European Respiratory Society/Japanese Respiratory Society/ American 
Latin Thoracic Association (ATS/ERS/JRS/ALAT) guidelines (2018) (3)  
- 
IPF disease diagnosis within the past 5 years 
- 
Usual Interstitial Pneumonia (UIP) on HRCT scan. 
- 
Recent lung function criteria: 
 Forced vital capacity (FVC) >40% of predicted value. 
 Carbon monoxide diffusing lung capacity (DLco) corrected for haemoglobin 
>30% of predicted value 
 

 
 
 
 
 
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5.2 Inclusion criteria for Sarcoidosis 
- 
Adult male or female patients aged 18 years and over 
- 
Women of childbearing age should not be pregnant, planning to get pregnant or breast-
feeding.  
 
- 
Clinical symptoms, CT scan and biopsy diagnosis of sarcoidosis 
- 
Patients with lung parenchymal disease and pulmonary stage II or more 
- 
Recent lung function criteria 
 
FVC>50% predicted 
 
DLCO >40% predicted 
5.3 Inclusion criteria for Healthy Volunteers 
- 
Age between 40 to 85 years, age and sex to match the group with IPF 
- 
Healthy subjects without any diseases that may cause inflammation 
- 
Women of childbearing age should not be pregnant, planning to get pregnant or 
breast-feeding.  
- 
Currently non-smokers: see exclusion criteria 
 
5.4 Exclusion Criteria 
5.4.1 Exclusion Criteria for probable IPF and Sarcoidosis Patients 
 
Respiratory Conditions other than IPF or sarcoidosis: 
- 
Confirmed diagnosis of occupational lung disease 
- 
Drug-induced lung disease or hypersensitivity pneumonitis 
- 
Lung and systemic autoimmune disease including connective tissue disease. 
Patients with an auto-immune profile considered diagnostic for a specific connective 
tissue disease will be excluded, even in the absence of    systemic symptoms. Non-
specific rises in auto antibodies e.g. rheumatoid factor; anti-nuclear antibody etc. will 
not be used to exclude individuals from the study. 
- 
Asbestosis or other asbestos related disease (pleural plaques, mesothelioma, 
asbestos pleural effusions) 
- 
Granulomatous lung disease. 
- 
Pulmonary artery hypertension (PAH) requiring a specific treatment.  
- 
Predominant chronic obstructive pulmonary disease (COPD) with forced expiratory 
volume in 1 second /forced vital capacity (FEV1/FVC) <0.70. 
- 
Patients with active tuberculosis or incompletely treated latent tuberculosis infection 
- 
Lung cancer 
- 
Upper respiratory tract infections in the past 6 weeks. 
 
Systemic Conditions 
 

 
 
 
 
 
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- 
History of vasculitis, autoimmune or connective tissue disease 
- 
Known human immunodeficiency virus (HIV) or chronic viral hepatitis  
- 
Clinically significant diseases (other than IPF or sarcoidosis) that may alter 
respiratory biomarkers: including other respiratory, gastrointestinal, endocrine, 
haematological, cardiovascular, genitourinary, skin or neurological diseases. 
- 
Recent or ongoing malignant diseases. 
- 
Significant nasal anatomical defects preventing nasal sampling: including 
hypertrophy of turbinates, major septum deviation, nasal polyposis or recurrent 
sinusitis and nasal mucosal defects 
 
Bronchoscopy Contraindications 
 
Any contra-indication to bronchoscopy as set out in British Thoracic Society guidelines (34) 
 
Smoking  
 
A detailed smoking history will be taken from all participants: to include total pack years, 
smoking in the past year, and smoking in the past 2 weeks. 
The history will include cigarettes, pipe smoking, cigars, vaping, and shisha. 
Any form of smoking is not permitted within 2 weeks of bronchoscopy. 
 
5.4.2  
Exclusion Criteria for Healthy Volunteers  
 
 
Current inflammatory/ immunological conditions. Any clinically significant diseases that 
may alter respiratory biomarkers: including respiratory, gastrointestinal, endocrine, 
haematological, cardiovascular, genitourinary, skin or neurological diseases. 
 
Recent or ongoing malignant diseases. 
 
Significant nasal anatomical defects preventing nasal sampling: including hypertrophy 
of turbinates, major septum deviation, nasal polyposis or recurrent sinusitis and nasal 
mucosal defects 
 
Upper respiratory tract infections in the past 6 weeks. 
 
Cigarette smoking:   
 
 
 
no cigarettes in the last 2 weeks 
 
 
 
not more than 10 cigarettes in the past year 
 
 
 
<10 year lifetime pack history of smoking 
 
5.4.3         Drug Therapy and Concomitant Medication 
 
The following therapy is not allowed for all study population groups:  
 
Any drugs that may in the opinion of the investigators influence biomarkers of 
inflammation and fibrosis.  
 
Pirfenidone, 
azathioprine, 
cyclophosphamide, 
cyclosporine 
A, 
oral 
steroids, 
Methotrexate, chemotherapy for 3 months 
 
Treatment with anticoagulant and anti-platelet therapy  
 
Inhaled steroids for 7 days 
 
Prescribed anti-inflammatories, salicylates, indomethacin within 7 days 

 
 
 
 
 
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Page 17 of 30      
 
Over-the-counter (OTC) medications taken within 7 days 
5.5 Withdrawal Criteria 
Any clinically significant side effects during procedures or withdrawal of consent by the patient 
/volunteer will necessitate study withdrawal. Patients /Participants will be informed that 
withdrawal from the study will not affect the care they receive now or in the future and that 
they are permitted to ask for all previously retained identifiable samples to be destroyed. 
However, we will inform participants that any samples collected prior to withdrawal will still be 
used unless they specifically ask for destruction of these samples 
All clinical activities will discontinue if there are adverse events related to the sampling 
procedures performed as part of the study as judged by the, Study Physician and/or the 
Principal Investigator. In this case participants will be followed up to optimum resolution of 
the adverse event. If a participant lost capacity to consent during the study, they would be 
withdrawn from the study. Identifiable data or tissue already collected with consent would be 
retained and used in the study. No further data or tissue would be collected or any other 
research procedures carried out on or in relation to the participant. 
6 ADVERSE EVENTS 
6.1 Definitions 
   
Adverse Event (AE): any untoward medical occurrence in a patient or clinical study subject.   
 
Serious Adverse Event (SAE): any untoward and unexpected medical occurrence or effect 
that: 
 
Results in death 
 
Is life-threatening - refers to an event in which the subject was at risk of death at 
the time of the event; it does not refer to an event which hypothetically might have 
caused death if it were more severe 
 
Requires hospitalisation, or prolongation of existing inpatients’ hospitalisation 
 
Results in persistent or significant disability or incapacity 
 
Is a congenital anomaly or birth defect 
 
Medical judgement should be exercised in deciding whether an AE is serious in all situations.  
Important AEs that are not immediately life-threatening or do not result in death or 
hospitalisation but may jeopardise the subject or may require intervention to prevent one of 
outcomes listed in the definition above, should also be considered serious. 
6.2 Reporting Procedures 
All adverse events should be reported. Depending on the nature of the event the reporting 
procedures below should be followed. Any questions concerning adverse event reporting 
should be directed to the Chief Investigator in the first instance.   
6.2.1 Non Serious AES 
All such events, whether expected or not, should be recorded.   

 
 
 
 
 
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6.2.2 Serious AES 
An SAE form should be completed and faxed to the Chief Investigator within 24 hours. 
However, relapse and death due to a pre-existing condition, and hospitalisations for elective 
treatment of a pre-existing condition do not need reporting as SAEs but should be recorded 
as AEs. 
 
All SAEs should be reported to the Wales RECs 7 Research Ethics Committee where the 
Chief Investigator considers the event to be: 
 ‘related’, i.e. resulted from the administration of any of the research procedures; and 
 ‘unexpected’, i.e. an event that is not listed in the protocol as an expected occurrence 
 
Reports of related and unexpected SAEs should be submitted within 15 days of the Chief 
Investigator becoming aware of the event, using the Report of Serious Adverse Event (non-
CTIMP) Form. The Chief Investigator must also notify the Sponsor of all SAEs. 
 
 
7 ASSESSMENT AND FOLLOW-UP  
7.1 Visits and study procedures for probable IPF and Sarcoidosis patients 
Visit 1  
The first visit will be on the day of the scheduled bronchoscopy and the following procedures 
will be carried out:  
 Medical history:  
Personal details date of birth, next of kin, and gender, ethnicity and contact details will 
be collected. 
 History relating to general health, allergies and drugs (prescription, over the counter 
and/or herbal medication/ vitamins) will also be collected  
 
 Smoking History 
A detailed smoking history will be recorded in terms of pack years, start date, current 
smoking (past 3 months) 
 
Contact details for reporting SAEs Fax: 020 331 25751, attention  
Please send SAE forms to: Imperial Clinical Respiratory Research Unit 
(ICRRU) 
St, Mary’s Hospital 
Mint Wing, First Floor, Entrance C 
Paddington 
London 
W2 1NY 
Tel: 020 331 25744 (Mon to Fri 09.00 – 17.00) 

 
 
 
 
 
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 Physical and nasal examination:  
The study doctor will perform a general physical examination including examination of 
heart and lungs. In addition, the physician will check the nose to make sure that nasal 
structure is normal and nasal passages are not blocked. 
 
 Vital signs:  
Blood pressure, heart rate, respiratory rate and temperature will be checked 
Participant’s height and weight will be checked 
 
 Blood: 
As part of the bronchoscopy patients will have a cannula (small tube) inserted into a 
vein in the arm to administer medications such as sedatives. When this has been 
inserted a sample of blood sample (approximately 25 ml) will be withdrawn from the 
tube. 
 
 Urine Sample:  
Patients will be asked to provide a sample of urine for safety checks and pregnancy 
testing in women of child bearing age.  
 
 Nasosorption or nasal mucosal lining fluid absorption:  
We will use a small strip of absorbent material on a handle to soak up fluid from the 
inside surface of the nostril (see photograph in Figure 1). This will be placed inside the 
nostril and left for 60 seconds, keeping light pressure with a finger to absorb fluid 
before being removed. This technique is very gentle and minimises rubbing and 
brushing inside the nostril. 
 
 
Figure 1: Nasosorption 
 
 Lung function test: Spirometry 
This is one of the most common lung function tests. It measures how much air the 
patient can inhale and exhale. It also measures how fast they can empty the air out of 
their lungs. Spirometry is used to help diagnose breathing problems such as asthma 
and chronic obstructive pulmonary disease (COPD). This test will only be performed 
if the doctor feels that it is required 
 
 Bronchosorption or bronchial lining fluid absorption: 
As the bronchoscope is passed into the airway, a small strip of absorptive paper is 
placed on the surface of the airway for up to 1 minute in a similar way to the nasal 
lining fluid absorption (see photograph in Figure 2). This is a new technique and will 
be performed by an experienced respiratory physician. The sampling device is a 

 
 
 
 
 
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Page 20 of 30      
specially designed medical device that has been produced by an authorised medical 
device company according to Medical Device Manufacturing Standards.  
 
 
Figure 2: Bronchosorption 
 
 Bronchoalveolar Lavage (BAL):  
  During the clinical bronchoscopy, if the doctor intends to collect a bronchial wash                   
sample (BAL), then a small proportion of this fluid will be collected for the study. 
 
Visits 2 and 3  
 
These are follow-up visits, which will take place 3 and 6 months after the bronchoscopy. 
Both visits will take place at the Imperial College Respiratory Research Unit at St Mary’s 
Hospital, Paddington, London or in the Out -Patient Clinic. Blood, Urine and nasosorption 
samples will be collected as per visit 1 schedule. 
Please see below a summary of study activities 
7.1.1 Schedule of assessments for probable IPF and Sarcoidosis patients 
 
Visit 1 
Baseline 
Bronchoscopy 
Visit 2 
3 months 
12-13 weeks 
post bronchoscopy 
Visit 3 
6 months 
24-26 weeks, 
post bronchoscopy 
at 
Bronchoscopy 
suite at St 
Mary’s Hospital 
at Out Patients Clinic at St Mary’s Hospital 
or ICRRU 
Lung function tests (including 
spirometry and DLco) 
X 
(X) 
where clinically 
indicated 
(X) 
where clinically 
indicated 
Urine  
X 
X 
X 
Serum (10 ml) 
for Biomarkers 
X 
X 
X 
Whole blood for RNA  
 
1st visit (10 ml) 
 
2nd and 3rd visits  
 
miRNA (plasma) and mRNA (gene expression) 
X 
X 
X 
Whole blood for DNA (5 ml) 
X 
 
 

 
 
 
 
 
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Upper 
Respiratory Tract 
sampling 
Nasosorption  
(2 samples) 
X 
X 
X 
Bronchoscopy 
X 
 
 
Lower 
Respiratory Tract 
sampling 
Bronchosorption 
(up to 6samples) 
X 
 
Bronchoalveolar 
lavage (BAL) 
X 
7.2 Visits and study procedures for healthy volunteers 
Participants will be required to attend ICRRU on a single day for up to 3 hours. The visit will 
involve the following; 
 
 Medical history:  
 Personal details date of birth, next of kin, and gender, ethnicity and contact details will 
be collected. 
 History relating to  general health, allergies and  drugs (prescription, over the counter 
and/or herbal medication/ vitamins) will also be collected  
 
 Smoking History 
A detailed smoking history will be recorded in terms of pack years, start date, current 
smoking (past 3 months) 
 
 Physical and nasal examination: 
The study doctor will perform a general physical examination including examination of 
heart and lungs. In addition, the physician will check the nose to make sure that nasal 
structure is normal and nasal passages are not blocked. 
 
 Vital signs:  
Blood pressure, heart rate, respiratory rate and temperature will be checked 
Participants’ height and weight will be checked 
The following samples will be collected in the same way as described in section 7 above 
 Blood tests 
 Urine Sample 
 Nasosorption  
Please note there will NOT be any bronchoscopy performed on healthy volunteers.  
 
7.2.1 Incidental findings for healthy volunteers 
The study physician will discuss any incidental findings with the participant at point of 
discovery. With the participant’s permission these will be communicated to the participant’s 
General Practitioner where necessary. The study Physician will also institute urgent 
treatment measures as appropriate. 

 
 
 
 
 
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Page 22 of 30      
 
7.2.2 Schedule of assessments for healthy volunteers 
 
Sample Management 
7.3 Sample Storage and Destruction 
Samples collected will be stored up to 10 years, or unless the participants specifically 
requests that the samples be destroyed, or local laws require destruction of the samples. 
Samples may also be used in future ethically approved studies where the participants have 
given written consent. However, if samples have been analysed prior to withdrawal, results 
from the analysis will remain part of the overall research data. 
 
 
 
Data arising from sample analysis, including data on germline mutations, will be subject to 
confidentiality standards.  
7.4 Serum 
Fill a 10 ml serum separator tube (SST) completely. It is important to thoroughly mix the blood 
with the clotting activation agent by inverting the tube not less than five times. Allow blood to 
clot for 30-60 minutes (tube standing upright). Centrifuge at 1500 x g (± 200 x g) for 15 
minutes until clot and serum are separated by a well-formed polymer barrier. 
 
Within 20 minutes of the end of centrifugation, use a pipette provided to transfer all serum 
(upper layer) into an appropriately - labelled 10 ml intermediate tube. Close the cap and invert 
the tube 10 times to mix the serum. 
 
Use pipette to transfer 1 ml of the serum into each of the four polypropylene tubes labelled 
"Split 1" through "Split 5".  
Freeze all samples immediately at -80°C until the time of shipment on dry ice.  
Study procedures 
Visit 1 
at  
 ICRRU, St Mary’s Hospital, 
Paddington, London 
up to 3 hours 
Inclusion and exclusion criteria 
review 
Blood for serum (10ml) 
X 
Urine  
X 
Whole blood for RNA (10ml) 
X 
Whole blood for DNA (5ml) 
X 
Nasosorption (left and right nostrils) 
X 

 
 
 
 
 
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7.5 Whole Blood 
7.5.1 Whole blood for DNA 
 
 
Draw 5 ml blood into 6 ml EDTA tube using standard venepuncture techniques. Mix the blood 
tube gently by gently inverting tube 5-10 times. Do not shake. Inadequate mixing may result 
in platelet clumping, clotting and/or incorrect test results. Freeze the sample at -20°C as soon 
as possible after the draw (must be within 24 hours of draw). Samples should be stored at -
80°C until the time of shipment; however, to reduce the risk of tubes cracking, freeze at -20°C 
first.  
 
7.5.2 Whole blood for RNA  
NOTE: You must NOT draw blood directly from the needle into the PAXgeneTM Blood RNA 
tube. You must NOT use a syringe to draw blood and then add it to the tube. 
1. After prepping the venepuncture site with an antiseptic and applying a tourniquet, 
insert the butterfly needle into the patient’s vein. 
2. It is important that the PAXgeneTM Blood RNA tubes are at room temperature (18-
25° C) prior to use. 
3. Fill all required collection tubes, leaving the 2.5 ml PAXgeneTM Blood RNA tubes as 
the FINAL TUBES to be collected. 
4. Hold the PAXgeneTM Blood RNA tube vertically, below the patient’s arm to avoid air 
being transferred into the PAXgeneTM tube or possible backflow from the tube. 
5. Ensure that blood has stopped flowing into the PAXgeneTM Blood RNA tube before 
removing the tube from the holder (at least 10 seconds). 
6. Gently invert both PAXgeneTM Blood RNA tubes 8-10 times. 
7. Store the PAXgeneTM Blood RNA tubes upright at room temperature (18-25° C) for 
2-3 hours before freezing. 
8. Freeze at -20°C until shipment.  
9. Place a layer of paper towel between the samples and the dry ice. 
WARNING: The contents of the PAXgeneTM tube are irritating to the eyes, respiratory 
system and skin. Refer to the PAXgeneTM Blood RNA Product Circular Section IV 
(Warnings) in the event of an exposure. 
7.6 Airway SAM samples 
1. Insert each bronchial SAM into a 2 mL micro-centrifuge tube, along with 300μl of 
Millipore buffer. 
2. Vortex mix the sample for 30 s to wash the SAM of loosely attached fluids and 
biomolecules. 
3. To ensure full sample recovery, perform centrifugal elution by adding the moist SAM 
to a spin filter mini-column that inserts into the same 2 mL micro-centrifuge tube 
used for washing. 
4. Use sterilized forceps to transfer the moist SAM to the spin filter. Change forceps 
between samples to prevent contamination. 
5. Centrifuge samples for 20 min at 16,000 x g in a mini-centrifuge cooled to 4 °C. 
6. Aliquot sample eluate as required and freeze at -80 °C 
Further details can be found in the manuscript Thwaites et al., 2018 J. Vis. Exp. (131) (35). 

 
 
 
 
 
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7.7 BAL samples 
BAL samples will be placed immediately on ice following collection. The total volume 
recovered will be recorded. In the laboratory, BAL samples will be centrifuged at 1200g for 
10 minutes. Supernatant will be aliquoted and stored at -80 ºC. Cell pellets from BAL will be 
resuspended in a total of 500µl RNA later and stored at -80 ºC. 
7.8 Urine Sample 
1. Collect a clean catch urine sample into collection cup & store at 4°C (2-4hrs max)  
2. Transfer urine into a sterile 50mL screw top plastic centrifuge tube  
3. Centrifuge the sample at 1,300xg, 20min, room temperature 
4. Decant the supernatant into a new conical tube (being careful not to disturb the pellet 
in the bottom of the tube) 
5. Prepare 5 aliquots of 1mL of the supernatant in low protein binding tubes (GNE 
usually provides these) 
6. Freeze aliquots at -80°C 
7.9 Laboratory Procedures, Storage and Shipment 
Samples will be barcoded and metadata (including patient number, collection date, sample 
type, 
SAM/aliquot 
#) 
will 
be 
captured 
by 
laboratory 
personnel 
in 
internal 
database/spreadsheet. 
 
Mucosal lining fluid samples will be collected and initially stored frozen at -80 °C without 
elution. Hence all nasosorption and bronchosorption samples will be stored as non-eluted 
“samples on SAM” at -80°C in SMH. Prior to shipment to the USA, samples may be eluted 
and aliquoted according to an agreed elution protocol with a specified buffer at SMH. The 
weight of nasosorption samples will be recorded. 
 
Serum and urine samples will be aliquoted into 1 ml before storing at -80C to avoid repeated 
freeze/thaw cycles. 
 
Shipment to Genentech/Roche will be on dry ice. Serum (at least 2ml), Nasosorption (2 
SAMs), Bronchosorption (4 SAMs) and BAL will be shipped in two batches; once when all 
baseline samples have been collected for all patients and once after all time-points (3 months 
and 6 months) have been collected. 
 
8 STATISTICS AND DATA ANALYSIS 
8.1 Sample Size 
As previously stated, this is an exploratory biomarker study involving measuring biomarkers 
of fibrosis in airway mucosal samples (nasosorption and bronchosorption) collected from 
patients with probable IPF and sarcoidosis compared to healthy volunteers. It is not 
possible to perform a sample size calculation at this stage, since we do not currently know 
the magnitude of biomarker differences in nasosorption and bronchosorption samples. 
Having performed this study, it is hoped that on the basis of particular biomarkers in defined 

 
 
 
 
 
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Page 25 of 30      
airway mucosal samples, we can provide sample size calculations for future studies of 
airway biomarkers in IPF.  
8.2 Interim Analysis 
The total study involves a total of 30 subjects with probable IPF, 15 patients with sarcoidosis 
and 15 healthy volunteers. Recruitment for this study is likely to take between 12 and 24 
months. An interim analysis at 12 months will be able to identify any emerging differences in 
biomarkers between the groups, and allow the nature of biomarkers of inflammation to be 
adjusted prior to the final analyses. In an exploratory study of novel methods of mucosal 
sampling in probable IPF and sarcoidosis, we do not know the rate of recruitment, and would 
prefer not to specify an exact number of patients for when interim analysis is performed. 
 
8.3 Statistical Analysis 
Data and all appropriate documentation will be stored for up to 10 years after the completion 
of the study, including the follow-up period.   
 
The major data will be levels of mediators: periostin, surfactant protein (SPD), CCL18 and 
CXCL13 in blood and bronchial lining fluid. 
 
We shall perform a test of distribution of data (Shapiro-Wilks test) to check normality of data 
to ensure appropriate statistical tests are applied to the data. 
 
We shall make individual x-y plots for mediators displaying levels for each individual subject 
within the patient groups (Probable IPF and sarcoidosis) and healthy controls 
 
Summary Statistics 
 Normal data with graphs with means and standard error of means (SEM) 
 Non-normal data with graphs with medians, quartiles and ranges (box-whisker) 
 
Paired or unpaired t-tests/ANOVA (or equivalent non-parametric tests) will be used to 
compare mediator levels in blood and airway mucosal lining fluid within groups over time or 
between different groups at a single time point. 
 
Correlations will be performed to compare mediator levels in blood, and upper and lower 
airway mucosal lining fluid samples and clinical parameters in patient groups and healthy 
controls. 
 
Other graphical and analyses methods like heat maps, violin plots, clustering, multivariate 
analyses and ROC curves will be used as appropriate.   
 
A P value of <0.05 is considered significant. 

 
 
 
 
 
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Page 26 of 30      
9 REGULATORY ISSUES 
This study will adhere to the principles outlined in ICH-GCP Guideline originating from the 
Declaration of Helsinki, 1964 and all amendments as well and the UK Policy Framework for 
Health and Social Care Research. It will be conducted in compliance with the protocol, the 
General Data Protection Regulation GDPR (2018), Human Tissue Act (2004) and other 
regulatory requirements as appropriate. The Chief Investigator has obtained approval from 
the Health Research Authority and Research Ethics Committee. The Chief Investigator will 
also require NHS Capacity and Capability Confirmation letter before accepting participants 
into the study. Samples and clinical data will be shared with Genentech (South San 
Francisco, California, USA) 
9.1 Consent 
Consent to enter the study must be sought from each participant only after a full explanation 
has been given, a Participant Information Sheet offered and enough time allowed for the 
participant to consider. Signed participant consent should be obtained. The right of the 
participant to refuse to participate without giving reasons must be respected. After the 
participant has entered the study the clinician remains free to give alternative treatment to 
that specified in the protocol at any stage if he/she feels it is in the participant’s best interests, 
and the reasons for doing so should be fully documented. In such cases the participants 
remain in the study for the purposes of follow-up and data analysis.  All participants are free 
to withdraw at any time from the study without giving reasons and without prejudicing further 
treatment and care. If a participant lost capacity to consent during the study, they would be 
withdrawn from the study. Identifiable data or tissue already collected with consent would be 
retained and used in the study. No further data or tissue would be collected or any other 
research procedures carried out on or in relation to the participant. 
 
9.2 Confidentiality 
Participants’ identification data will be required for the registration process. The Study 
Coordination Centre will preserve the confidentiality of participants taking part in the study 
and is registered under the General Data Protection Regulation (GDPR) 2018. 
9.3 Indemnity 
Imperial College London holds negligent harm and non-negligent harm insurance policies 
which apply to this study. 
9.4 Sponsor 
Imperial College London will act as the main Sponsor for this study. Delegated responsibilities 
will be assigned to the NHS Trust taking part in this study.   
9.5 Funding 
Genentech, San Francisco, California, USA is funding this study. 

 
 
 
 
 
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Page 27 of 30      
9.6 Audits  
The study may be subject to inspection and audit by Imperial College London under their 
remit as sponsor and other regulatory bodies to ensure adherence to GCP and the UK Policy 
Framework for Health and Social Care Research 
10 STUDY MANAGEMENT 
The day-to-day management of the study will be co-ordinated by the ICRRU unit coordinator 
and the delegated Clinical Research Fellow with close support from Prof Trevor Hansel of 
ICRRU at St Mary’s Hospital.   
10.1 Sample Shipment 
Serum, nasosorption samples, bronchosorption samples, and BAL samples will be shipped 
to Genentech, San Francisco, California, USA at the end of the study. The samples will be 
shipped in 2 batches; once when all baseline samples have been collected for all patients 
and again after all time-points (3 months and 6 months) have been collected. 
 
11 PUBLICATION POLICY 
Our aim is to ensure the full dissemination of all study results in medical publications of the 
highest impact and citation factor. Individual subjects will be strictly anonymised. 
 
 

 
 
 
 
 
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