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

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.

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.

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