Efficacy and Safety Study of Orvepitant for Chronic Cough in Patients With Idiopathic Pulmonary Fibrosis (IPF-COMFORT)

A Double-Blind, Randomised, Placebo Controlled, Two Period Cross-Over Study to Evaluate the Efficacy and Safety of Orvepitant in Chronic Cough in Patients With Idiopathic Pulmonary Fibrosis

ORV-PF-01 is a two way, placebo controlled, cross-over study, to evaluate the effect of two doses of orvepitant on cough in patients with IPF.

Study Overview

• Status: Active, not recruiting
• Conditions: Cough; Idiopathic Pulmonary Fibrosis
• Intervention / Treatment: Drug: Orvepitant Maleate; Drug: Placebo

Detailed Description

The study will be a multi-center, double-blind, randomised, placebo-controlled 2-period cross-over study in subjects with chronic cough due to idiopathic pulmonary fibrosis (IPF).

Subjects will participate in one of two cohorts (Cohort 1 and Cohort 2). Cohort 1 will evaluate a 30 mg orvepitant dose and Cohort 2 the 10 mg dose. Within each cohort, subjects will be randomised to receive either orvepitant or placebo in the first treatment period (Treatment Period A) followed by the alternate treatment in Treatment Period B. There will be a wash-out period of 3 weeks between the two treatment periods. Subjects will be randomised 1:1 to each of the two treatment orders and 1:1 to each cohort.

Subjects will enter a screening period of between 14 and 28 days to determine eligibility. Eligible subjects will be randomised at the Baseline visit and will participate in two identical 28 day treatment periods with the wash-out period between them. There will be a total of 8 visits including the Screening, Baseline and final Follow-up visits.

• Study Type: Interventional
• Enrollment (Estimated): 88
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: NeRRe Therapeutics Chief Medical Officer; Phone Number: +44 (0) 1438 906960; Email: info@nerretherapeutics.com

Study Locations

• Netherlands
  • Heerlen, Netherlands, 6419 PC
    • Zuyderland Medical Centre
  • Nieuwegein, Netherlands, 3435 CM
    • Sint Antonius Hospital
  • Rotterdam, Netherlands, 3015 GD
    • Erasmus University Medical Centre
  • Zwolle, Netherlands, 8025 AB
    • Isala Ziekenhuis
• United Kingdom
  • Birmingham, United Kingdom, B9 5SS
    • Heartlands Hospital
  • Cambridge, United Kingdom, CB2 0AY
    • Royal Papworth Hospital
  • Exeter, United Kingdom, EX2 5DW
    • Royal Devon and Exeter Hospital
  • London, United Kingdom, SE1 9RT
    • Guy's Hospital
  • Manchester, United Kingdom, M13 9NQ
    • MAC Clinical Research
  • Nottingham, United Kingdom, NG5 1PB
    • Nottingham City Hospital
  • Southampton, United Kingdom, SO16 6YD
    • Southampton General Hospital
  • Berkshire
    • Reading, Berkshire, United Kingdom, RG1 5AN
      • Royal Berkshire Hospital
  • Hull
    • Cottingham, Hull, United Kingdom, HU16 5JQ
      • Castle Hill Hospital
  • Merseyside
    • Prescot, Merseyside, United Kingdom, L34 1BH
      • MAC Clinical Research
  • Northern Ireland
    • Antrim, Northern Ireland, United Kingdom, BT41 2RL
      • Antrim Area Hospital
    • Derry, Northern Ireland, United Kingdom, BT47 6SB
      • Altnagelvin Area Hospital
  • Oxford
    • Headington, Oxford, United Kingdom, OX3 7LE
      • Churchill Hospital
  • Perth And Kinross
    • Perth, Perth And Kinross, United Kingdom, PH1 1NX
      • Perth Royal Infirmary
  • Scotland
    • Edinburgh, Scotland, United Kingdom, EH16 4SA
      • Royal Infirmary of Edinburgh
  • South Yorkshire
    • Barnsley, South Yorkshire, United Kingdom, S75 3DL
      • MAC Clinical Research
  • West Yorkshire
    • Leeds, West Yorkshire, United Kingdom, LS10 1DU
      • MAC Clinical Research
• United States
  • California
    • Los Angeles, California, United States, 90033
      • University of Southern California
    • San Francisco, California, United States, 94143
      • University of California
  • Colorado
    • Denver, Colorado, United States, 80206
      • National Jewish Health
  • Illinois
    • Maywood, Illinois, United States, 60153
      • Loyola University Chicago
  • Maryland
    • Silver Spring, Maryland, United States, 20904
      • Jadestone Clinical Research, LLC
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • North Carolina
    • Charlotte, North Carolina, United States, 28277
      • American Health Research
    • Greensboro, North Carolina, United States, 27403
      • Pulmonix, LLC
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University
  • South Carolina
    • Charleston, South Carolina, United States, 29424
      • Medical University of South Carolina
  • Tennessee
    • Nashville, Tennessee, United States, 37204
      • Vanderbilt University Medical Center
  • Texas
    • Dallas, Texas, United States, 75246
      • Baylor University
    • Webster, Texas, United States, 77598
      • Clear Lake Health
  • Utah
    • Salt Lake City, Utah, United States, 84108
      • University of Utah
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia Health System

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Diagnosis of IPF established according to the 2018 or 2022 joint ATS/ERS/JRS/ALAT Clinical Practice Guideline
• FEV1/FVC ratio ≥0.65 at the screening visit
• Haemoglobin-corrected diffusion capacity of carbon monoxide (Hb-corrected DLCO) ≥25% within 12 months of the screening visit
• Arterial oxygen saturation on room air or oxygen ≥90% at Screening
• Life expectancy of at least 12 months
• Cough that is attributed to IPF, which has not responded to anti-tussive treatment, and which has been present for at least 8 weeks prior to Screening
• Mean daily IPF Coughing Severity Scale score ≥5 (after rounding) during the second week of the baseline assessment period

Key Exclusion Criteria:

• Recent respiratory tract infection (<8 weeks prior to Screening)
• Recent acute exacerbation of IPF (<8 weeks prior to Screening)
• Current smokers or ex-smokers with <6 months' abstinence prior to Screening
• Emphysema ≥50% on high-resolution computed tomography, or the extent of emphysema is greater than the extent of fibrosis according to the reported results of the most recent scan
• Mean early morning cough scale score ≥5 and rest of the day cough scale score <5 (after rounding) during the second week of the baseline assessment period (assessed at Visit 2)
• Cough that is predominantly productive in nature and attributable to lung pathology such as chronic bronchitis or bronchiectasis

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Orvepitant 30mg; Orvepitant 30mg tablet once daily for 4 weeks	Drug: Orvepitant Maleate; Orvepitant tablets 30mg or 10mg
Experimental: Orvepitant 10mg; Orvepitant 10mg tablet once daily for 4 weeks	Drug: Orvepitant Maleate; Orvepitant tablets 30mg or 10mg
Placebo Comparator: Placebo; Placebo tablet once daily for 4 weeks	Drug: Placebo; Placebo tablets to match orvepitant 30mg and 10mg tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean change from Baseline in weekly average of the daily Idiopathic Pulmonary Fibrosis Coughing Severity Scale	A numerical rating scale from 0 (no coughing) to 10 (coughing as bad as you can imagine)	Week 4

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean change from Baseline in weekly average of the early morning IPF Coughing Severity Scale	A numerical rating scale from 0 (no coughing) to 10 (coughing as bad as you can imagine)	Week 4
Mean change from Baseline in weekly average of the rest of the day IPF Coughing Severity Scale	A numerical rating scale from 0 (no coughing) to 10 (coughing as bad as you can imagine)	Week 4
Mean change from Baseline in weekly average of the daily urge to cough scale	A numerical rating scale from 0 (no urge to cough) to 10 (urge to cough as bad as you can imagine)	Week 4
Mean change from Baseline in weekly average of the daily cough frequency scale	A numerical rating scale from 0 (no coughing) to 10 (coughing as often as you can imagine)	Week 4
Mean change from Baseline in weekly average of the daily dyspnoea scale	A numerical rating scale from 0 (no shortness of breath) to 10 (shortness of breath as bad as you can imagine)	Week 4
Mean change from Baseline in 24-hour cough frequency	Cough frequency assessed using an ambulatory cough monitoring device	Week 4
Mean change from Baseline in awake cough frequency	Cough frequency assessed using an ambulatory cough monitoring device	Week 4
Mean change from Baseline in night-time cough frequency	Cough frequency assessed using an ambulatory cough monitoring device	Week 4
Mean change from Baseline in the number of coughing bouts	Cough frequency assessed using an ambulatory cough monitoring device	Week 4

Collaborators and Investigators

• Sponsor: Nerre Therapeutics Ltd.
• Collaborators: Pharm-Olam International
• Investigators: Principal Investigator: Prof. S. Birring, MB ChB, MD, Department of Respiratory Medicine, King's College Hospital, London UK

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2022
• Primary Completion (Estimated): June 1, 2024
• Study Completion (Estimated): June 1, 2024

Study Registration Dates

• First Submitted: December 23, 2021
• First Submitted That Met QC Criteria: December 23, 2021
• First Posted (Actual): January 11, 2022

Study Record Updates

• Last Update Posted (Actual): February 26, 2024
• Last Update Submitted That Met QC Criteria: February 23, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Signs and Symptoms, Respiratory; Lung Diseases, Interstitial; Fibrosis; Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis; Cough; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Maleic acid
• Other Study ID Numbers: ORV-PF-01

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