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

Sponsor

Nerre Therapeutics Ltd. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05185089

Collaborator

Pharm-Olam International (Industry)

Enrollment

Locations

Arms

Anticipated Duration (Months)

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Cough Idiopathic Pulmonary Fibrosis	Drug: Orvepitant Maleate Drug: Placebo	Phase 2

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

Study Type:

Interventional

Anticipated Enrollment :

88 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

Double-blind

Primary Purpose:

Treatment

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

Actual Study Start Date :

Aug 1, 2022

Anticipated Primary Completion Date :

Dec 1, 2023

Anticipated Study Completion Date :

Dec 1, 2023

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

40 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Key Inclusion Criteria:

Diagnosis of IPF established according to the 2018 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 ≥5.0 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 ≥5.0 and rest of the day cough scale score <5 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Southern California	Los Angeles	California	United States	90033
2	University of California	San Francisco	California	United States	94143
3	National Jewish Health	Denver	Colorado	United States	80206
4	Loyola University Chicago	Maywood	Illinois	United States	60153
5	University of Michigan	Ann Arbor	Michigan	United States	48109
6	Mayo Clinic	Rochester	Minnesota	United States	55905
7	American Health Research	Charlotte	North Carolina	United States	28277
8	PulmonIx, LLC	Greensboro	North Carolina	United States	27403
9	Temple University	Philadelphia	Pennsylvania	United States	19140
10	Medical University of South Carolina	Charleston	South Carolina	United States	29424
11	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37204
12	Baylor University	Dallas	Texas	United States	75246
13	Clear Lake Health	Webster	Texas	United States	77598
14	University of Utah	Salt Lake City	Utah	United States	84108
15	University of Virginia Health System	Charlottesville	Virginia	United States	22908
16	Zuyderland Medical Centre	Heerlen		Netherlands	6419 PC
17	Sint Antonius Hospital	Nieuwegein		Netherlands	3435 CM
18	Erasmus University Medical Centre	Rotterdam		Netherlands	3015 GD
19	Isala Ziekenhuis	Zwolle		Netherlands	8025 AB
20	Castle Hill Hospital	Cottingham	Hull	United Kingdom	HU16 5JQ
21	MAC Clinical Research	Prescot	Merseyside	United Kingdom	L34 1BH
22	Churchill Hospital	Headington	Oxford	United Kingdom	OX3 7LE
23	MAC Clinical Research	Barnsley	South Yorkshire	United Kingdom	S75 3DL
24	MAC Clinical Research	Leeds	West Yorkshire	United Kingdom	LS10 1DU
25	Royal Devon and Exeter Hospital	Exeter		United Kingdom	EX2 5DW
26	Guy's Hospital	London		United Kingdom	SE1 9RT
27	MAC Clinical Research	Manchester		United Kingdom	M13 9NQ
28	North Tyneside General Hospital	North Shields		United Kingdom	NE29 8NH
29	Southampton General Hospital	Southampton		United Kingdom	SO16 6YD

Sponsors and Collaborators

Nerre Therapeutics Ltd.
Pharm-Olam International

Investigators

Principal Investigator: Prof. S. Birring, MB ChB, MD, Department of Respiratory Medicine, King's College Hospital, London UK

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Nerre Therapeutics Ltd.

ClinicalTrials.gov Identifier:

NCT05185089

Other Study ID Numbers:

ORV-PF-01

First Posted:

Jan 11, 2022

Last Update Posted:

Aug 17, 2022

Last Verified:

Aug 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Pulmonary Fibrosis

Cough

Idiopathic Pulmonary Fibrosis

Fibrosis

Maleic acid

Study Results

No Results Posted as of Aug 17, 2022