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

October 24, 2025 updated by: Nerre Therapeutics Ltd.

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

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
80

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

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
      • Londonderry, 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

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Mean Change From Baseline in Weekly Average of the Daily Idiopathic Pulmonary Fibrosis Coughing Severity Scale (IPF CSS)
Time Frame: Week 4
A numerical rating scale from 0 (no coughing) to 10 (coughing as bad as you can imagine) for coughing severity in the last 24 hours
Week 4

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Mean Change From Baseline in Weekly Average of the Early Morning IPF Coughing Severity Scale
Time Frame: Week 4
A numerical rating scale from 0 (no coughing) to 10 (coughing as bad as you can imagine) for coughing severity first thing in the morning
Week 4
Mean Change From Baseline in Weekly Average of the Rest of the Day IPF Coughing Severity Scale
Time Frame: Week 4
A numerical rating scale from 0 (no coughing) to 10 (coughing as bad as you can imagine) for severity of any other coughing during the last 24 hours, excluding coughing first thing in the morning
Week 4
Mean Change From Baseline in Weekly Average of the Daily Urge to Cough Scale
Time Frame: Week 4
A numerical rating scale from 0 (no urge to cough) to 10 (urge to cough as bad as you can imagine) for severity of urge to cough in the last 24 hours
Week 4
Mean Change From Baseline in Weekly Average of the Daily Cough Frequency Scale
Time Frame: Week 4
A 5-point verbal rating scale for cough frequency over the last 24 hours with response options from 'never' to 'all the time'. The verbal responses were converted to a number (0 = never, 4 = all the time).
Week 4
Mean Change From Baseline in Weekly Average of the Daily Dyspnoea Scale
Time Frame: Week 4
A numerical rating scale from 0 (no shortness of breath) to 10 (shortness of breath as bad as you can imagine) for severity of shortness of breath in the last 24 hours
Week 4
Mean Change From Baseline in Leicester Cough Questionnaire (LCQ) Total Score
Time Frame: Week 4
The LCQ is a 19-item questionnaire that assesses cough-related Quality-of-Life. It has three domains (physical, psychological and social). The total score range is 3-21 and domain scores each range from 1-7; a higher score indicates a better Quality-of-Life. This outcome measure is the mean change from Baseline to Week 4 in the total score.
Week 4
Mean Change From Baseline in Leicester Cough Questionnaire (LCQ) Physical Domain Score
Time Frame: Week 4
The LCQ is a 19-item questionnaire that assesses cough-related Quality-of-Life. It has three domains (physical, psychological and social). The total score range is 3-21 and domain scores each range from 1-7; a higher score indicates a better Quality-of-Life. This outcome measure is the mean change from Baseline to Week 4 in the physical domain score.
Week 4
Mean Change From Baseline in Leicester Cough Questionnaire (LCQ) Psychological Domain Score
Time Frame: Week 4
The LCQ is a 19-item questionnaire that assesses cough-related Quality-of-Life. It has three domains (physical, psychological and social). The total score range is 3-21 and domain scores each range from 1-7; a higher score indicates a better Quality-of-Life. This outcome measure is the mean change from Baseline to Week 4 in the psychological domain score.
Week 4
Mean Change From Baseline in Leicester Cough Questionnaire (LCQ) Social Domain Score
Time Frame: Week 4
The LCQ is a 19-item questionnaire that assesses cough-related Quality-of-Life. It has three domains (physical, psychological and social). The total score range is 3-21 and domain scores each range from 1-7; a higher score indicates a better Quality-of-Life. This outcome measure is the mean change from Baseline to Week 4 in the social domain score.
Week 4
Mean Change From Baseline in 24-hour Cough Frequency
Time Frame: Week 4
Cough frequency assessed using an ambulatory cough monitoring device (Leicester Cough Monitor)
Week 4
Mean Change From Baseline in Awake Cough Frequency
Time Frame: Week 4
Cough frequency assessed using an ambulatory cough monitoring device (Leicester Cough Monitor)
Week 4
Mean Change From Baseline in Night-time Cough Frequency
Time Frame: Week 4
Cough frequency assessed using an ambulatory cough monitoring device (Leicester Cough Monitor)
Week 4
Mean Change From Baseline in the Number of Coughing Bouts
Time Frame: Week 4
Cough frequency assessed using an ambulatory cough monitoring device (Leicester Cough Monitor)
Week 4
Mean Change From Baseline in the Number of Coughs Per Bout
Time Frame: Week 4
Cough frequency assessed using an ambulatory cough monitoring device (Leicester Cough Monitor)
Week 4

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Nerre Therapeutics Ltd.

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Pharm-Olam International

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Prof. S. Birring, MB ChB, MD, Department of Respiratory Medicine, King's College Hospital, London UK

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 1, 2022

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 5, 2024

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 19, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 23, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 23, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 11, 2022

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 10, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 24, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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