A multi-center, longitudinal 12-week pilot study to evaluate cough severity and its impact, utilizing a next generation cough monitor, in participants with idiopathic pulmonary fibrosis (IPF) or Non IPF Pulmonary Fibrosis

Interstitial lung diseases (ILDs) encompass a large group of over 200 pulmonary
disorders, characterized by abnormalities in the distal lung parenchyma.
Irrespective of the underlying pathophysiology, the resulting alteration of the
interstitial space leads to clinical symptoms such as dyspnoea and cough and
physiologic abnormalities such as restrictive ventilatory deficit on pulmonary
function testing.

Idiopathic pulmonary fibrosis (IPF) is the most common and the most severe of
the chronic fibrosing ILDs, and the epidemiology of this disease and its course
are relatively well documented. Epidemiological data and understanding of other
forms of fibrosing ILD other than IPF is limited to date, in part due to the
complex nature of these diseases and their rarity. In patients with IPF,
refractory cough is one of the most important and burdensome symptoms.

In patients with non-IPF forms of pulmonary fibrosis, persistent cough is also
a commonly reported symptom. The mechanisms of increased cough in this
population are also not well understood. The incidence of persistent and
disruptive cough in this patient population, the cough pattern and frequency,
as well as the impact of cough on quality of life, are not well-described.
Notably, cough has been shown to be an independent predictor of disease
progression in patients with IPF. In persons with fibrosing forms of ILD,
including IPF, worse cough specific QoL (as measured by the Leicester Cough
Questionnaire [LCQ]), was associated with higher risk of death, lung
transplantation and respiratory hospitalization.

It has been hypothesized that cough may enhance fibrotic remodeling via cough
induced mechanical stretch and stress. Further physiologic consequences of
cough, have not been well investigated. In sum, a better understanding of cough
frequency and intensity across patients with pulmonary fibrosis and its
relation to functional and physiologic parameters is important to elucidate its
potential
association with disease progression.

As highlighted, significant gaps in knowledge remain regarding etiology of
cough, consequences of cough and appropriate treatment of cough in patients
with pulmonary fibrosis. A further understanding of the similarities and
differences in cough among persons with Non IPF Pulmonary Fibrosis and IPF,
together with insight into the pattern and impact of cough in these patients is
required. The current pilot aims to assess cough frequency, indirect measures
of cough intensity and the association between objective cough measures and
lung physiology, a host of patient-reported outcomes and blood-based biomarkers
in a patient cohort with Non IPF Pulmonary Fibrosis or IPF. This study aims to
expand the understanding of the disease and its symptoms, thereby narrowing the
existing gap in knowledge, and to help support the development of future
compounds targeting cough.

We will utilize a hybrid study design in which 4 visits will be conducted
remotely and all cough data will be captured via a wearable, digitally enabled
cough monitor with bluetooth capabilities that allow secure remote upload.
Furthermore, patients will perform videoassisted home spirometry. The intention
of incorporating 4 remote visits into the study design is to assess the
potential to ease the burden of study procedures on patients and physicians,
thereby broadening the subject pool to those who might otherwise not have
access to enroll in this pilot. If successful, this type of study design could
also be employed in Phase 2 and 3 interventional trials and allow a broader and
more racially, geographically, and socioeconomically diverse patient population
access to clinical trials.

The risks of utilizing a wearable cough monitor are minimal. Skin irritation
caused by the adhesive used to apply the device to the chest wall is possible,
though not anticipated, and if present would not be expected to be severe.
Continuous audio recordings may raise concern for privacy breaches and/or
inadvertent recording of conversations. The Strados RESP biosensor data is
fully encrypted on device and in transit to prevent unauthorized access to
health information. Strados RESP does not contain an open-air microphone and is
not designed to acquire speech or other sounds from a patient's mouth. It is
intended to acquire sounds of the lungs and airways including cough sounds,
wheeze sounds and normal breath
sounds. The file is reversed to avoid discernible speech (if incidentally
acquired) being interpretable during a QA/QC session in addition to a speech
filter being applied to the raw transmission data to remove speech signatures
from review. Files are broken up into short <60 second segments to reduce the
risk further of any post-processed file containing discernible speech over a
long enough period of time to capture private conversations and
information.

This pilot study offers patients a unique opportunity to utilize emerging,
wearable, digital technology for remote monitoring of what is typically a quite
vexing symptom (cough). Additionally, patients will have the opportunity to
utilize video assisted home spirometry to minimize on site visits. Other data
derived from the cough monitor may also inform disease assessment in future
clinical care, though may not be of imminent benefit to patients in the
study.