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

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

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.

Study Overview

• Status: Terminated
• Conditions: Chronic Cough; IPF; Persistent Cough in IPF
• Intervention / Treatment: Drug: RVT-1601; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 108
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Royal Prince Alfred Hospital
    • Westmead, New South Wales, Australia, 2145
      • Westmead Hospital
  • Quensland
    • Chermside, Quensland, Australia, 4032
      • Lung Research Quensland
    • South Brisbane, Quensland, Australia, 4101
      • Mater Research
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital
  • Victoria
    • Frankston, Victoria, Australia, 3199
      • Frankston Hospital-Peninsula Health
    • Heidelberg, Victoria, Australia, 3084
      • Austin Hospital
    • Westmead, Victoria, Australia, 3004
      • Alfred Health
  • Western Australia
    • Murdoch, Western Australia, Australia, 6150
      • Fiona Stanley Hospital
    • Perth, Western Australia, Australia, 6150
      • TrialsWest
• Belgium
  • Brussel, Belgium
    • University Clinic Saint-Luc
  • Leuven, Belgium
    • Universitaire Ziekenhuizen Leuven
• Canada
  • Halifax, Canada
    • Dalhousie University
  • Hamilton, Canada
    • McMaster University
  • Montréal, Canada
    • Centre Hospitalier Universitaire de Montréal
  • Toronto, Canada
    • University Health Network, Toronto General Hospital
  • Vancouver, Canada
    • St. Paul's Hospital
• Czechia
  • Prague, Czechia
    • Thomayer Hospital
• Germany
  • Berlin, Germany
    • Evangelische Lungerklinik Berlin
  • Bonn, Germany
    • University Clinic Bonn
  • Essen, Germany
    • Ruhrlandklinik-Universitätsmedizin Essen
  • Greifenstein, Germany
    • Pneumologische Klinik Waldhof Elgerhausen
  • Hannover, Germany
    • Medizinische Hochshule Hannover
  • Heidelberg, Germany
    • University Heidelberg
  • Immenhausen, Germany
    • Lungenfachklinik Immenhausen
  • Solingen, Germany
    • Krankenhaus Bethanian
• Italy
  • Bologna, Italy
    • Bologna University Hospital
  • Catania, Italy
    • University of Catania
  • Modena, Italy
    • A.O.U. Policlinico di Modena
  • Padova, Italy
    • University of Padova
  • Roma, Italy
    • Fondazione Policlinico Universitario Agostino Gemelli
  • Siena, Italy
    • Siena University Hospital
  • Torino, Italy
    • University of Torino
• Netherlands
  • Amsterdam, Netherlands
    • VU Medical Center
  • Den Haag, Netherlands
    • Haaglanden Medical Center
  • Heerlen, Netherlands
    • Zuyderland Medical Center
  • Nieuwegein, Netherlands
    • St. Antonius Ziekenhuis
  • Rotterdam, Netherlands
    • Erasmus Medical Center
• New Zealand
  • Auckland, New Zealand
    • Greenlane Clinical Center
  • Christchurch, New Zealand
    • University of Otago
  • Hamilton, New Zealand
    • Waikato Hospital
• Turkey
  • Adana, Turkey
    • Cukurova University
  • Istanbul, Turkey
    • Istanbul University Istanbul Medical Faculty
  • İzmir, Turkey
    • Ege University Hospital
• United Kingdom
  • Cambridge, United Kingdom
    • Royal Papworth Hospital
  • Edinburgh, United Kingdom
    • University of Edinburgh
  • Leicester, United Kingdom
    • University of Leicester
  • Liverpool, United Kingdom
    • University Hospital Aintree
  • London, United Kingdom
    • Royal Brompton Hospital
  • Manchester, United Kingdom
    • University of Manchester
  • Nottingham, United Kingdom
    • Nottingham University Hospital
  • Southampton, United Kingdom
    • University Hospital Southampton
  • East Yorkshire
    • Cottingham, East Yorkshire, United Kingdom
      • Castle Hill Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama
  • California
    • Sacramento, California, United States, 95817
      • University of California Davis
    • San Francisco, California, United States, 94143
      • University California San Francisco
  • Colorado
    • Denver, Colorado, United States, 80206
      • National Jewish Health
  • Florida
    • Jacksonville, Florida, United States, 32204
      • Ascension Medical Group / St. Vincent's Lung Institute
    • Miami, Florida, United States, 33136
      • University of Miami
    • Ocala, Florida, United States, 34470
      • Renstar Medical Research
    • Tampa, Florida, United States, 33606
      • Tampa General Hospital / Uni of South Florida
  • Illinois
    • Maywood, Illinois, United States, 60153
      • Loyola University
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Tulane University
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • Johns Hopkins University School of Medicine
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Universty of Michigan
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic - Rochester
  • Missouri
    • Chesterfield, Missouri, United States, 63017
      • St. Luke's Hospital
  • New York
    • New York, New York, United States, 10065
      • Cornell University Weill Cornell Medical College
  • North Carolina
    • Charlotte, North Carolina, United States, 28207
      • American Health Research
    • Durham, North Carolina, United States, 27710
      • Duke University
    • Greensboro, North Carolina, United States, 27403
      • PulmonIx, LLC
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University School of Medicine
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
    • Spartanburg, South Carolina, United States, 29303
      • Spartanburg Medical Research
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Texas
    • Dallas, Texas, United States, 75390
      • UT Southwester Medical Center
  • Utah
    • Salt Lake City, Utah, United States, 84103
      • University of Utah Hospitals & Clinics
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • University of Virginia
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 89 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

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

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in forced vital capacity (FVC)	FVC measured as the total amount of air exhaled during pulmonary function test.	12 weeks
Change in disease-specific QoL	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.	12 weeks
Change in airway and lung volumes as measured by HRCT images	HRCT-based functional respiratory imaging (FRI) parameters measured at end-inspiration and end-expiration.	12 weeks
Change in biomarkers	Collagen degradation by-products measured in the blood.	12 weeks
Change in respiratory-related QoL	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.	12 weeks
Change in dyspnea score	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).	12 weeks

Collaborators and Investigators

• Sponsor: Respivant Sciences GmbH
• Collaborators: Respivant Sciences Inc.
• Investigators: Study Director: Ahmet Tutuncu, MD, PhD, Respivant Sciences Inc.

Study record dates

Study Major Dates

• Study Start (Actual): March 29, 2019
• Primary Completion (Actual): May 29, 2020
• Study Completion (Actual): June 5, 2020

Study Registration Dates

• First Submitted: March 2, 2019
• First Submitted That Met QC Criteria: March 4, 2019
• First Posted (Actual): March 6, 2019

Study Record Updates

• Last Update Posted (Actual): June 11, 2020
• Last Update Submitted That Met QC Criteria: June 8, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: Cough; IPF; Chronic Cough; IPF Cough
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Signs and Symptoms, Respiratory; Cough
• Other Study ID Numbers: RVT1601-CC-04

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No