Chronic Cough, IPF, Persistent Cough in IPF
Conditions
Keywords
Cough, Chronic Cough, IPF, IPF Cough
Brief summary
Idiopathic pulmonary fibrosis (IPF) is a rare, progressive life-threatening disease that is characterized by exertional dyspnea and persistent dry cough. Cough in IPF is both a presenting and a complicating clinical feature, which affects approximately three quarters of IPF cases. It is often a debilitating symptom that adversely affects quality of life (QoL) and is usually refractory to medical therapy. Inhaled RVT-1601 (formerly, PA101B), a new inhalation formulation of cromolyn sodium delivered via the eFlow® Closed System (CS) nebulizer, is being evaluated in this Phase 2b study for the treatment of persistent cough in patients with IPF.
Interventions
DRUGRVT-1601
Inhaled RVT-1601 administered TID via eFlow nebulizer
DRUGPlacebo
Inhaled Placebo administered TID via eFlow nebulizer
Sponsors
Respivant Sciences Inc.
Respivant Sciences GmbH
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Randomization stratified by background IPF therapy use and FVC % predicted at baseline
Eligibility
Sex/Gender
ALL
Age
40 Years to 89 Years
Healthy volunteers
No
Inclusion criteria
* Male or female subjects age 40 through 89 years * Confirmed diagnosis of IPF with clinical features consistent with the current clinical practice guidelines * Persistent cough for at least 8 weeks that is primarily due to IPF and not responsive to anti-tussive therapy * Daytime cough severity score of ≥ 40 mm on a 100-mm VAS * 24-hour average cough count of at least 10 coughs per hour * Forced Vital Capacity (FVC) \> 45% predicted value within 4 weeks * Diffusion capacity for carbon monoxide corrected for hemoglobin (DLCOc) \> 30% predicted value within 4 weeks * Life expectancy of at least 12 months
Exclusion criteria
* Current or recent history of clinically significant medical condition, laboratory abnormality, or illness that could place the subject at risk or compromise the quality of the study data * Significant coronary artery disease (i.e., myocardial infarction within 6 months or unstable angina within 1 month) * Upper or lower respiratory tract infection within 4 weeks * Acute exacerbation of IPF within 6 months * Lung transplantation expected within 12 months * Requiring supplemental O2 \> 4 litres/min to maintain peripheral arterial O2 saturation (SpO2) \> 88% at rest * History of malignancy likely to result in significant disability or likely to require significant medical or surgical intervention within the next 2 years * Current smoker (i.e., use of tobacco products within the last 3 months) * Current or recent history of drug or alcohol abuse within 12 months * Participation in any other investigational drug study within 4 weeks * Use of certain drugs for cough management within 4 weeks: prednisone, opiates, baclofen, gabapentin, pregabalin, thalidomide, amitriptyline, inhaled corticosteroids, or inhaled bronchodilators * Use of ACE inhibitors or cromolyn sodium within 4 weeks * Females who are pregnant or breastfeeding, or if of child-bearing potential unwilling to practice acceptable means of birth control during the study * History of hypersensitivity or intolerance to cromolyn sodium
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in 24-hour average cough count | 12 weeks | Objective cough count monitoring performed using a digital recording device. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in cough severity | 12 weeks | Cough severity assessed using Visual Analog Scale (VAS), a single-item questionnaire using 100-point scale ranging from 0 (no cough) to 100 (extremely severe cough). |
| Change in cough-specific QoL | 12 weeks | Cough-specific QoL assessed using Leicester Cough Questionnaire (LCQ), a 19-item questionnaire designed to measure impact of cough in three domains (physical, psychological and social), each domain ranging from 1 to 7 and LCQ total score ranging from 3 to 21, with the higher scores corresponding with better QoL. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change in biomarkers | 12 weeks | Collagen degradation by-products measured in the blood. |
| Change in forced vital capacity (FVC) | 12 weeks | FVC measured as the total amount of air exhaled during pulmonary function test. |
| Change in dyspnea score | 12 weeks | Dyspnea score assessed using University of California San Diego (UCSD) Shortness of Breath Questionnaire (SOBQ),a 24-item questionnaire designed to measure breathlessness on a scale from 0 (not at all breathless) to 5 (maximally breathless or too breathless to do the activity). |
| Change in respiratory-related QoL | 12 weeks | Respiratory-related QoL assessed using St. George's Respiratory Questionnaire (SGRQ), a 50-item questionnaire designed to measure impact of respiratory symptoms on overall health, daily life, and perceived well-being, with total score ranging from 0 to 100 and lower score denoting a better health status. |
| Change in disease-specific QoL | 12 weeks | Disease-specific QoL assessed using King's Brief Interstitial Lung Disease Questionnaire (K-BILD), a 15-item questionnaire designed to measure impact of interstitial lung disease in three domains (breathlessness and activities, psychological and chest symptoms), each domain and total score ranging from 0 to 100 with the higher scores corresponding with better QoL. |
| Change in airway and lung volumes as measured by HRCT images | 12 weeks | HRCT-based functional respiratory imaging (FRI) parameters measured at end-inspiration and end-expiration. |
Countries
Australia, Belgium, Canada, Czechia, Germany, Italy, Netherlands, New Zealand, Turkey (Türkiye), United Kingdom, United States
Outcome results
None listed