CoughPhase 2IPF-COMFORTNCT05185089
Efficacy and Safety Study of Orvepitant for Chronic Cough in Patients With Idiopathic Pulmonary Fibrosis
A Phase 2 study testing Orvepitant Maleate in people with Cough and Idiopathic Pulmonary Fibrosis, run by Nerre Therapeutics Ltd. at 37 sites in 3 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 40 years and older
- Conditions the study is for
- Cough, Idiopathic Pulmonary Fibrosis
- What is being tested?
- Orvepitant Maleate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 80 participants
- Where
- 37 sitesin 3 countries
- Study dates
- 1 Aug 2022to 19 Jun 2024
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
37 sites in 3 countries.
37 sites in 3 countries
United Kingdom17 sites
Antrim Area Hospital
Antrim, Northern Ireland, BT41 2RL
MAC Clinical Research
Barnsley, South Yorkshire, S75 3DL
Heartlands Hospital
Birmingham, B9 5SS
Royal Papworth Hospital
Cambridge, CB2 0AY
Castle Hill Hospital
Cottingham, Hull, HU16 5JQ
Royal Infirmary of Edinburgh
Edinburgh, Scotland, EH16 4SA
Royal Devon and Exeter Hospital
Exeter, EX2 5DW
Churchill Hospital
Headington, Oxford, OX3 7LE
MAC Clinical Research
Leeds, West Yorkshire, LS10 1DU
Guy's Hospital
London, SE1 9RT
Altnagelvin Area Hospital
Londonderry, Northern Ireland, BT47 6SB
MAC Clinical Research
Manchester, M13 9NQ
Nottingham City Hospital
Nottingham, NG5 1PB
Perth Royal Infirmary
Perth, Perth and Kinross, PH1 1NX
MAC Clinical Research
Prescot, Merseyside, L34 1BH
Royal Berkshire Hospital
Reading, Berkshire, RG1 5AN
Southampton General Hospital
Southampton, SO16 6YD
United States16 sites
University of Michigan
Ann Arbor, Michigan, 48109
Medical University of South Carolina
Charleston, South Carolina, 29424
American Health Research
Charlotte, North Carolina, 28277
University of Virginia Health System
Charlottesville, Virginia, 22908
Baylor University
Dallas, Texas, 75246
National Jewish Health
Denver, Colorado, 80206
PulmonIx, LLC
Greensboro, North Carolina, 27403
University of Southern California
Los Angeles, California, 90033
Loyola University Chicago
Maywood, Illinois, 60153
Vanderbilt University Medical Center
Nashville, Tennessee, 37204
Temple University
Philadelphia, Pennsylvania, 19140
Mayo Clinic
Rochester, Minnesota, 55905
University of Utah
Salt Lake City, Utah, 84108
University of California
San Francisco, California, 94143
Jadestone Clinical Research, LLC
Silver Spring, Maryland, 20904
Clear Lake Health
Webster, Texas, 77598
Netherlands4 sites
Zuyderland Medical Centre
Heerlen, 6419 PC
Sint Antonius Hospital
Nieuwegein, 3435 CM
Erasmus University Medical Centre
Rotterdam, 3015 GD
Isala Ziekenhuis
Zwolle, 8025 AB
About this study
Official title: 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.
Read the 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.
- Conditions
- Cough, Idiopathic Pulmonary Fibrosis
- Being tested
- Orvepitant Maleate, Placebo
- Medical subject headings
- Cough, Idiopathic Pulmonary Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Orvepitant MaleateDrug
Orvepitant tablets 30mg or 10mg
PlaceboDrug
Placebo tablets to match orvepitant 30mg and 10mg tablets
| Study group | Role | What they receive |
|---|---|---|
| Orvepitant 30mg | Experimental | Orvepitant 30mg tablet once daily for 4 weeks Receives: Drug: Orvepitant Maleate |
| Orvepitant 10mg | Experimental | Orvepitant 10mg tablet once daily for 4 weeks Receives: Drug: Orvepitant Maleate |
| Placebo | Placebo comparator | Placebo tablet once daily for 4 weeks Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean Change From Baseline in Weekly Average of the Daily Idiopathic Pulmonary Fibrosis Coughing Severity Scale (IPF CSS)
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
Measured: Week 4
Secondary outcomes (14)
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) for coughing severity first thing in the morning
Measured: 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) for severity of any other coughing during the last 24 hours, excluding coughing first thing in the morning
Measured: 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) for severity of urge to cough in the last 24 hours
Measured: Week 4
Mean Change From Baseline in Weekly Average of the Daily Cough Frequency Scale
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).
Measured: 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) for severity of shortness of breath in the last 24 hours
Measured: Week 4
Mean Change From Baseline in Leicester Cough Questionnaire (LCQ) Total Score
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.
Measured: Week 4
Mean Change From Baseline in Leicester Cough Questionnaire (LCQ) Physical Domain Score
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.
Measured: Week 4
Mean Change From Baseline in Leicester Cough Questionnaire (LCQ) Psychological Domain Score
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.
Measured: Week 4
Mean Change From Baseline in Leicester Cough Questionnaire (LCQ) Social Domain Score
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.
Measured: Week 4
Mean Change From Baseline in 24-hour Cough Frequency
Cough frequency assessed using an ambulatory cough monitoring device (Leicester Cough Monitor)
Measured: Week 4
Mean Change From Baseline in Awake Cough Frequency
Cough frequency assessed using an ambulatory cough monitoring device (Leicester Cough Monitor)
Measured: Week 4
Mean Change From Baseline in Night-time Cough Frequency
Cough frequency assessed using an ambulatory cough monitoring device (Leicester Cough Monitor)
Measured: Week 4
Mean Change From Baseline in the Number of Coughing Bouts
Cough frequency assessed using an ambulatory cough monitoring device (Leicester Cough Monitor)
Measured: Week 4
Mean Change From Baseline in the Number of Coughs Per Bout
Cough frequency assessed using an ambulatory cough monitoring device (Leicester Cough Monitor)
Measured: Week 4
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jan 2022
- Study start1 Aug 2022
- Primary completion5 Jun 2024
- Study completion19 Jun 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for CoughStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 80 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nerre Therapeutics Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Pharm-Olam International
- Responsible party
- Sponsor
- Investigators
- Prof. S. Birring, MB ChB, MD, Principal investigator, Department of Respiratory Medicine, King's College Hospital, London UK
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05185089
- Sponsor's protocol ID
- ORV-PF-01
- Acronym
- IPF-COMFORT
- Status last verified
- Oct 2025
- First submitted
- 23 Dec 2021
- Last updated
- 10 Nov 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT05185089
- Acronym / sponsor ID
- IPF-COMFORT / ORV-PF-01
- Conditions
- Cough, Idiopathic Pulmonary Fibrosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 80 participants (actual)
- Lead sponsor
- Nerre Therapeutics Ltd.Industry (pharma, biotech, devices)
- Collaborators
- Pharm-Olam International
- Study start
- 1 Aug 2022 (actual)
- Primary completion
- 5 Jun 2024 (actual)
- Study completion
- 19 Jun 2024 (actual)
- First posted
- 11 Jan 2022 (actual)
- Results
- Posted 10 Nov 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Orvepitant 30mg | Experimental | Drug: Orvepitant MaleateOrvepitant 30mg tablet once daily for 4 weeks |
| Orvepitant 10mg | Experimental | Drug: Orvepitant MaleateOrvepitant 10mg tablet once daily for 4 weeks |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo tablet once daily for 4 weeks |
Who may qualify
- Ages
- 40 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (6 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Orvepitant MaleateOrvepitant tablets 30mg or 10mg | Drug | Orvepitant 10mg, Orvepitant 30mg |
| PlaceboPlacebo tablets to match orvepitant 30mg and 10mg tablets | Drug | Placebo |
Primary outcome
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
14 secondary outcomes
Mean Change From Baseline in Weekly Average of the Early Morning IPF Coughing Severity Scale
Time frame: Week 4
Mean Change From Baseline in Weekly Average of the Rest of the Day IPF Coughing Severity Scale
Time frame: Week 4
Mean Change From Baseline in Weekly Average of the Daily Urge to Cough Scale
Time frame: Week 4
Mean Change From Baseline in Weekly Average of the Daily Cough Frequency Scale
Time frame: Week 4
Mean Change From Baseline in Weekly Average of the Daily Dyspnoea Scale
Time frame: Week 4
Mean Change From Baseline in Leicester Cough Questionnaire (LCQ) Total Score
Time frame: Week 4
Mean Change From Baseline in Leicester Cough Questionnaire (LCQ) Physical Domain Score
Time frame: Week 4
Mean Change From Baseline in Leicester Cough Questionnaire (LCQ) Psychological Domain Score
Time frame: Week 4
Mean Change From Baseline in Leicester Cough Questionnaire (LCQ) Social Domain Score
Time frame: Week 4
Mean Change From Baseline in 24-hour Cough Frequency
Time frame: Week 4
Mean Change From Baseline in Awake Cough Frequency
Time frame: Week 4
Mean Change From Baseline in Night-time Cough Frequency
Time frame: Week 4
Mean Change From Baseline in the Number of Coughing Bouts
Time frame: Week 4
Mean Change From Baseline in the Number of Coughs Per Bout
Time frame: Week 4
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Nov 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Prof. S. Birring, MB ChB, MD principal investigator
Department of Respiratory Medicine, King's College Hospital, London UK
37 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Orvepitant Maleate in people with Cough and Idiopathic Pulmonary Fibrosis, run by Nerre Therapeutics Ltd. at 37 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 37 sites in United Kingdom, United States, Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Nov 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mean Change From Baseline in Weekly Average of the Daily Idiopathic Pulmonary Fibrosis Coughing Severity Scale (IPF CSS) (time frame: Week 4). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Nov 2025.