A Phase 2b Study of Inhaled RVT-1601 for the Treatment of Persistent Cough in IPF

Study Overview
=================
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.

Official Title
-----------------
Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging, Efficacy and Safety Study With Inhaled RVT-1601 for the Treatment of Persistent Cough in Patients With Idiopathic Pulmonary Fibrosis (IPF): SCENIC Trial

Conditions
-----------------
Persistent Cough in IPF, Chronic Cough, IPF

Intervention / Treatment
-----------------
* Drug: RVT-1601
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 40 Years
Maximum Age: 89 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomization stratified by background IPF therapy use and FVC % predicted at baseline
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RVT-1601 Low Dose<br> | Drug: RVT-1601<br>* Inhaled RVT-1601 administered TID via eFlow nebulizer<br>|
| Experimental: RVT-1601 Mid Dose<br> | Drug: RVT-1601<br>* Inhaled RVT-1601 administered TID via eFlow nebulizer<br>|
| Experimental: RVT-1601 High Dose<br> | Drug: RVT-1601<br>* Inhaled RVT-1601 administered TID via eFlow nebulizer<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Inhaled Placebo administered TID via eFlow nebulizer<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in 24-hour average cough count | Objective cough count monitoring performed using a digital recording device. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in cough severity | 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). | 12 weeks | 
| Change in cough-specific QoL | 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. | 12 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Cough, Chronic Cough, IPF, IPF Cough