Clinical trial NCT05185089: Efficacy and Safety Study of Orvepitant for Chronic Cough in Patients With Idiopathic Pulmonary Fibrosis
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cough
Idiopathic Pulmonary Fibrosis
Lead sponsor: Nerre Therapeutics Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Pharm-Olam International
First posted: 2022-01-11
Enrollment: 80
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Mean change from Baseline in weekly average of the daily Idiopathic Pulmonary Fibrosis Coughing Severity Scale
timeFrame: Week 4
Secondary outcomes:
measure: Mean change from Baseline in weekly average of the early morning IPF Coughing Severity Scale
timeFrame: Week 4
measure: Mean change from Baseline in weekly average of the rest of the day IPF Coughing Severity Scale
timeFrame: Week 4
measure: Mean change from Baseline in weekly average of the daily urge to cough scale
timeFrame: Week 4
measure: Mean change from Baseline in weekly average of the daily cough frequency scale
timeFrame: Week 4
measure: Mean change from Baseline in weekly average of the daily dyspnoea scale
timeFrame: Week 4
measure: Mean change from Baseline in 24-hour cough frequency
timeFrame: Week 4
measure: Mean change from Baseline in awake cough frequency
timeFrame: Week 4
measure: Mean change from Baseline in night-time cough frequency
timeFrame: Week 4
measure: Mean change from Baseline in the number of coughing bouts
timeFrame: Week 4
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: San Francisco
country: United States
facility: University of California
state: California
city: Denver
country: United States
facility: National Jewish Health
state: Colorado
city: Maywood
country: United States
facility: Loyola University Chicago
state: Illinois
city: Silver Spring
country: United States
facility: Jadestone Clinical Research, LLC
state: Maryland
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Charlotte
country: United States
facility: American Health Research
state: North Carolina
city: Greensboro
country: United States
facility: PulmonIx, LLC
state: North Carolina
city: Philadelphia
country: United States
facility: Temple University
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: Baylor University
state: Texas
city: Webster
country: United States
facility: Clear Lake Health
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia Health System
state: Virginia
city: Heerlen
country: Netherlands
facility: Zuyderland Medical Centre
city: Nieuwegein
country: Netherlands
facility: Sint Antonius Hospital
city: Rotterdam
country: Netherlands
facility: Erasmus University Medical Centre
city: Zwolle
country: Netherlands
facility: Isala Ziekenhuis
city: Reading
country: United Kingdom
facility: Royal Berkshire Hospital
state: Berkshire
city: Cottingham
country: United Kingdom
facility: Castle Hill Hospital
state: Hull
city: Prescot
country: United Kingdom
facility: MAC Clinical Research
state: Merseyside
city: Antrim
country: United Kingdom
facility: Antrim Area Hospital
state: Northern Ireland
city: Derry
country: United Kingdom
facility: Altnagelvin Area Hospital
state: Northern Ireland
city: Headington
country: United Kingdom
facility: Churchill Hospital
state: Oxford
city: Perth
country: United Kingdom
facility: Perth Royal Infirmary
state: Perth And Kinross
city: Edinburgh
country: United Kingdom
facility: Royal Infirmary of Edinburgh
state: Scotland
city: Barnsley
country: United Kingdom
facility: MAC Clinical Research
state: South Yorkshire
city: Leeds
country: United Kingdom
facility: MAC Clinical Research
state: West Yorkshire
city: Birmingham
country: United Kingdom
facility: Heartlands Hospital
city: Cambridge
country: United Kingdom
facility: Royal Papworth Hospital
city: Exeter
country: United Kingdom
facility: Royal Devon and Exeter Hospital
city: London
country: United Kingdom
facility: Guy's Hospital
city: Manchester
country: United Kingdom
facility: MAC Clinical Research
city: Nottingham
country: United Kingdom
facility: Nottingham City Hospital
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
Study officials:
affiliation: Department of Respiratory Medicine, King's College Hospital, London UK
name: Prof. S. Birring, MB ChB, MD
role: PRINCIPAL_INVESTIGATOR
References: