chronic cough idiopathic pulmonary fibrosis
Conditions
Interventions
Subjects will participate in one of two cohorts (Cohort 1 [30 mg] and Cohort 2
[10 mg]). Within each cohort, subjects will be randomised to receive either
orvepitant or placebo once daily in the fir
Sponsors
NeRRe Therapeutics Ltd
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Male and female subjects >=40 years of age. 2. Able to understand and comply with the requirements of the study and give informed consent. 3. Diagnosis of IPF established according to the 2018 joint ATS/ERS/JRS/ALAT Clinical Practice Guideline. 4. FEV1/FVC ratio >=0.65 at the screening visit. 5. Haemoglobin-corrected diffusion capacity of carbon monoxide (Hb-corrected DLCO) >=25% within 12 months of the screening visit1. 6. Arterial oxygen saturation on room air or oxygen >=90% at Screening. 7. Life expectancy of at least 12 months. 8. 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. 9. Mean daily IPF Coughing Severity Scale score >=5.0 during the second week of the baseline assessment period (assessed at Visit 2). 10. If taking pirfenidone or nintedanib2, the dose must have been stable dose for at least 3 months prior to Screening. 11. Female subjects must not be of child-bearing potential (i.e., they must be surgically sterilised or post-menopausal3). 12. Male subjects who have partners of child-bearing potential must agree to use a condom from the Baseline visit until 30 days after the last dose of study medication.
Exclusion criteria
Exclusion criteria: 1. Recent respiratory tract infection (=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. 5. 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). 6. Cough that is predominantly productive in nature and attributable to lung pathology such as chronic bronchitis or bronchiectasis. 7. Known clinically significant pulmonary hypertension (World Health Organisation functional class III or IV [and where functional limitation is due to PAH rather than IPF]). 8. A history of clinically relevant drug or alcohol abuse [according to Diagnostic and Statistical Manual of Mental Disorders 5 criteria (or later edition if applicable)] within 6 months before Screening. 9. Any other clinically significant or unstable medical or psychiatric condition that would, in the opinion of the investigator, interfere with the subject*s ability to participate safely in the study. 10. Any malignancy in the past 5 years unless non-invasive and in remission. Any malignancy diagnosed more than 5 years prior to screening must have been in complete remission for at least 5 years. Written approval must be obtained from the Sponsor for a subject with any history of malignancy. 11. Any clinically significant abnormal laboratory test result(s), measured at Screening. 12. Inability to comply with the use of prohibited and allowed medications as described below: a. Strong or moderate inhibitors of CYP3A4 are not allowed from Screening until 1 week after the last dose of study medication; b. Strong or moderate inducers of CYP3A4 are not allowed from Screening until 1 week after the last dose of study medication; c. Strong or moderate P-glycoprotein inhibitors are not allowed from Screening until 1 week after the last dose of study medication; d. Angiotensin converting enzyme (ACE) inhibitors are not allowed within 3 months of Screening and throughout the study; e. Other treatments for cough management (including opioids, dextromethorphan, gabapentin, pregabalin, baclofen, antihistamines, thalidomide or tricyclic antidepressants (e.g. amitriptyline)) are not allowed from 4 weeks before the Baseline visit until Visit 8. Medications in these classes may be continued provided they have been prescribed solely for the management of another comorbidity and the dose has been stable for at least 4 weeks before the screening visit. f. The use of other NK1 antagonists (eg aprepitant, fosaprepitant, rolapitant) is not permitted for any reason from 4 weeks before the Baseline visit until completion of Visit 8; g. Immune-suppressant drugs and systemic corticosteroids taken for co-morbidities are permitted provided the dose has been stable for at least 2 weeks before the screening visit and they are expected to be used at this dose throughout the study. Any other use is prohibited; h. Supplemental oxygen is permitted provided it has been used for at least 2 weeks before the screening visit and is e
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary endpoint is the mean change from Baseline (the last 7 days prior to randomisation) to Week 4 (the last 7 days of treatment) in weekly average of the daily IPF Coughing Severity Scale score. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary efficacy endpoints: • Mean change from Baseline to Week 2 in weekly average of the daily IPF Coughing Severity Scale • Mean change from Baseline to Weeks 2 and 4 in weekly average of the early morning cough scale • Mean change from Baseline to Weeks 2 and 4 in weekly average of the rest of the day cough scale • Mean change from Baseline to Weeks 2 and 4 in weekly average of the daily urge to cough scale • Mean change from Baseline to Weeks 2 and 4 in weekly average of the daily cough frequency scale • Mean change from Baseline to Weeks 2 and 4 in weekly average of the daily dyspnoea scale • Proportion of subjects in each category at Weeks 2 and 4 for each global rating of cough • Proportion of subjects in each category at Weeks 2 and 4 for each global rating of cough • Mean change from Baseline to Week 4 in 24-hour cough frequency • Mean change from Baseline to Week 4 in awake cough frequency • Mean change from Baseline to Week 4 in night-time cough frequency • Mean change from Baseline to Week 4 in the number of coughing bouts • Mean change from Baseline to Week 4 in LCQ total and domain (Physical, Social, Psychological) scores • Mean change from Baseline to Week 4 in K-BILD total and domain (Psychological, Breathlessness, Chest Symptoms) scores • Proportion of patients with a clinically relevant improvement in total K-BILD score • Mean change from Baseline to Week 4 in the PROMIS SF SD 8b score • Mean change from Baseline to Week 4 in the HADS score • Mean change from Baseline to Week 4 in the HARQ score Safety endpoints: • Change from Baseline in forced vital capacity (FVC), forced expired volume in one second (FEV1), peak expiratory flow rate and vital capacity (VC) • Number of treatment emergent adverse events • Number of treatment emergent serious adverse events • Number of treatment emergent adverse events resulting in treatment discontinuation • Severity of treatment emergent adverse events • Number of treatmen | — |
Countries
Netherlands
Outcome results
None listed