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Efficacy and Safety Study of Orvepitant for Chronic Cough in Patients With Idiopathic Pulmonary Fibrosis

Phase 2
Completed
Conditions
Cough
Idiopathic Pulmonary Fibrosis
Interventions
Registration Number
NCT05185089
Lead Sponsor
Nerre Therapeutics Ltd.
Brief 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.

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
80
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 & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
Orvepitant 30mgOrvepitant MaleateOrvepitant 30mg tablet once daily for 4 weeks
Orvepitant 10mgOrvepitant MaleateOrvepitant 10mg tablet once daily for 4 weeks
PlaceboPlaceboPlacebo tablet once daily for 4 weeks
Primary Outcome Measures
NameTimeMethod
Mean change from Baseline in weekly average of the daily Idiopathic Pulmonary Fibrosis Coughing Severity ScaleWeek 4

A numerical rating scale from 0 (no coughing) to 10 (coughing as bad as you can imagine)

Secondary Outcome Measures
NameTimeMethod
Mean change from Baseline in 24-hour cough frequencyWeek 4

Cough frequency assessed using an ambulatory cough monitoring device

Mean change from Baseline in night-time cough frequencyWeek 4

Cough frequency assessed using an ambulatory cough monitoring device

Mean change from Baseline in the number of coughing boutsWeek 4

Cough frequency assessed using an ambulatory cough monitoring device

Mean change from Baseline in weekly average of the early morning IPF Coughing Severity ScaleWeek 4

A numerical rating scale from 0 (no coughing) to 10 (coughing as bad as you can imagine)

Mean change from Baseline in weekly average of the daily cough frequency scaleWeek 4

A numerical rating scale from 0 (no coughing) to 10 (coughing as often as you can imagine)

Mean change from Baseline in weekly average of the daily urge to cough scaleWeek 4

A numerical rating scale from 0 (no urge to cough) to 10 (urge to cough as bad as you can imagine)

Mean change from Baseline in weekly average of the rest of the day IPF Coughing Severity ScaleWeek 4

A numerical rating scale from 0 (no coughing) to 10 (coughing as bad as you can imagine)

Mean change from Baseline in awake cough frequencyWeek 4

Cough frequency assessed using an ambulatory cough monitoring device

Mean change from Baseline in weekly average of the daily dyspnoea scaleWeek 4

A numerical rating scale from 0 (no shortness of breath) to 10 (shortness of breath as bad as you can imagine)

Trial Locations

Locations (34)

PulmonIx, LLC

🇺🇸

Greensboro, North Carolina, United States

Baylor University

🇺🇸

Dallas, Texas, United States

Jadestone Clinical Research, LLC

🇺🇸

Silver Spring, Maryland, United States

Vanderbilt University Medical Center

🇺🇸

Nashville, Tennessee, United States

Churchill Hospital

🇬🇧

Headington, Oxford, United Kingdom

University of Southern California

🇺🇸

Los Angeles, California, United States

Loyola University Chicago

🇺🇸

Maywood, Illinois, United States

National Jewish Health

🇺🇸

Denver, Colorado, United States

University of California

🇺🇸

San Francisco, California, United States

American Health Research

🇺🇸

Charlotte, North Carolina, United States

Clear Lake Health

🇺🇸

Webster, Texas, United States

Sint Antonius Hospital

🇳🇱

Nieuwegein, Netherlands

University of Utah

🇺🇸

Salt Lake City, Utah, United States

University of Virginia Health System

🇺🇸

Charlottesville, Virginia, United States

Isala Ziekenhuis

🇳🇱

Zwolle, Netherlands

MAC Clinical Research

🇬🇧

Manchester, United Kingdom

Royal Berkshire Hospital

🇬🇧

Reading, Berkshire, United Kingdom

Perth Royal Infirmary

🇬🇧

Perth, Perth And Kinross, United Kingdom

Heartlands Hospital

🇬🇧

Birmingham, United Kingdom

Nottingham City Hospital

🇬🇧

Nottingham, United Kingdom

Royal Papworth Hospital

🇬🇧

Cambridge, United Kingdom

Royal Devon and Exeter Hospital

🇬🇧

Exeter, United Kingdom

Southampton General Hospital

🇬🇧

Southampton, United Kingdom

Temple University

🇺🇸

Philadelphia, Pennsylvania, United States

Zuyderland Medical Centre

🇳🇱

Heerlen, Netherlands

Erasmus University Medical Centre

🇳🇱

Rotterdam, Netherlands

University of Michigan

🇺🇸

Ann Arbor, Michigan, United States

Mayo Clinic

🇺🇸

Rochester, Minnesota, United States

Altnagelvin Area Hospital

🇬🇧

Derry, Northern Ireland, United Kingdom

Antrim Area Hospital

🇬🇧

Antrim, Northern Ireland, United Kingdom

Medical University of South Carolina

🇺🇸

Charleston, South Carolina, United States

Royal Infirmary of Edinburgh

🇬🇧

Edinburgh, Scotland, United Kingdom

Guy's Hospital

🇬🇧

London, United Kingdom

Castle Hill Hospital

🇬🇧

Cottingham, Hull, United Kingdom

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