Active, not recruiting
Phase 2
Assess the Safety, Pharmacokinetics, Pharmacodynamics and Clinical Activity of RXC007 in Idiopathic Pulmonary Fibrosis
Condition(s) studied
IPFFibrosis
Investigational drug(s) / intervention(s)
RXC007Placebo
RXC007: RXC007 will be administered in the form of oral capsules at 3 potential dose levels: 20 mg, 50mg and 70 mg in 5 cohorts. 12 patients of cohorts 1, 2 and the Expansion cohort will receive RXC007. The Dosage regimen is BID or QD.
Placebo: The placebo will be administered in the form of oral capsules at each dose level to 4 of the 16 participants within cohorts 1, 2 and the Expansion cohort. The Dosage regimen is BID or QD
Study summary
The purpose of the study is to assess the safety and tolerability of RXC007 when given for 12 weeks (84 days), alone and in combination with nintedanib or pirfenidone.
Eligibility
Inclusion Criteria:
* Aged ≥40 to 80 years at the time of signing the informed consent.
* Diagnosis of IPF within 5 years of Screening based on the modified ATS/ERS/JRS/ALAT IPF guidelines for diagnosis and management of IPF (Raghu et al, 2018) and confirmed on independent central imaging review.
* Combination of HRCT pattern, as assessed by central reviewers, consistent with diagnosis of IPF (see the modified ATS/ERS/JRS/ALAT IPF guidelines \[Raghu et al, 2018\]).
* FVC % predicted ≥50% predicted of normal at Screening, with no clinically significant deterioration between the Screening Visit and randomisation, as determined by the Investigator.
* DLco (Hb-adjusted) at screening ≥30%.
* In the main study, participants receiving treatment for IPF with nintedanib or pirfenidone are allowed if on treatment for at least 3 months and on a stable dose for at least 4 weeks prior to Screening and during Screening.
* In patients who are not on any treatment for IPF but have previously received nintedanib or pirfenidone, there needs to be a washout period ≥4 weeks prior to Screening.
* No clinically significant abnormalities, in the opinion of the investigator, in vital signs (e.g., blood pressure, pulse rate, respiration rate, oral temperature) within 28 days before first dose of IMP.
Exclusion Criteria:
* Currently receiving or planning to initiate treatment for IPF with agents not approved for that indication.
* FEV1/FVC ratio \<0.7 at Screening, pre-bronchodilator use.
* Lower respiratory tract infection requiring antibiotics within 4 weeks of Screening or during Screening.
4\. The extent of emphysema in the lungs exceeds fibrosis, based on central review of HRCT scans.
* Need for continuous oxygen supplementation, defined as \>15 hours/day.
* Acute IPF exacerbation within 6 months of Screening or during Screening.
* Clinical diagnosis of any connective-tissue disease (including, but not limited to, scleroderma, polymyositis/dermatomyositis, systemic lupus erythematosus, and rheumatoid arthritis) or a diagnosis of interstitial pneumonia with autoimmune features as determined by the Investigator applying the recent ERS/ATS research statement \[Fischer et al 2015\]. Note: Serological testing is not needed if not clinically indicated.
* Disease other than IPF with a life expectancy of less than 12 weeks.
Additional exclusion criteria for the Translational Science Sub Study
* Participants with any contra-indication to bronchoscopy and alveolar lavage including tracheal stenosis, pulmonary hypertension, severe hypoxia, or hypercapnia.
* Patients in the sub study are not permitted to receive nintedanib or pirfenidone within 3 weeks of randomisation and throughout the Treatment period. (Note: background IPF treatment should not be stopped for the purpose of eligibility)
Primary outcome measure(s)
- Incidence and severity of AEs and SAEs Changes in safety laboratory parameters, vital signs, and ECGs — From Day 1 to post-study follow up visit (12 weeks)
The primary endpoints of the study include the incidence and severity of AEs and SAEs
- Number of participants who report a change from normal range values for laboratory safety parameters (serum biochemistry, serum haematology or urinalysis) from first dose on Day 1 to post-study follow up visit. — From Day 1 to post-study follow up visit (12 weeks)
This primary endpoint will report the number of participants within all cohorts of study who record a value which is deemed as outside of the normal range (regardless of clinical significance) for any of the serum biochemistry, serum haematology or urinalysis parameters as defined in the study protocol following first dose administration on Day 1 up to completion of the post-study visit
- Number of participants who report a change from normal range values for vital signs parameters (blood pressure, pulse rate, respiration rate, oral body temperature) from first dose on Day 1 to 12 weeks of treatment — From Day 1 to post-study follow up visit (12 weeks)
This primary endpoint will report the number of participants within all cohorts of the study who record a value which is deemed as outside of the normal range (regardless of clinical significance) for any of the vital signs parameters (systolic/diastolic blood pressure, pulse rate, respiration rate, oral body temperature) as defined in the study protocol following first dose administration on Day 1 up to completion of the post-study visit
- Number of participants who report a change from normal range values for any of the associated 12-Lead ECG parameters (heart rate, QT interval and QTcF interval) from first dose on Day 1 up to completion of the post-study visit. — From Day 1 to post-study follow up visit (12 weeks)
This primary endpoint will report the number of participants within all cohorts of the study who record a value which is deemed as outside of the normal range (regardless of clinical significance) for any of the 12-Lead ECG parameters (heart rate, QT interval and QTcF interval) as defined in the study protocol following first dose administration on Day 1 up to 12 weeks of treatment
Trial sites (31)
| Facility | City | Region | Status |
|---|
| Medical University of Vienna |
Vienna |
Austria |
|
| E PNE UZ Leuven |
Leuven |
Belgium |
|
| CHU De Liège |
Liège |
Belgium |
|
| Pneumologicka klinika 1.LF UK a |
Prague |
Czechia |
|
| Azienda Ospedaliero-Universitaria "Ospedali-Riuniti" di Ancona |
Ancona |
Italy |
|
| Azienda Ospedaliero Universitaria Policlinico ''G.Rodolico-San Marco'' |
Catania |
Italy |
|
| Colonello D'avanzo Hospital |
Foggia |
Italy |
|
| PO Vito Fazzi |
Lecce |
Italy |
|
| Ospedale S. Giuseppe Milano |
Milan |
Italy |
|
| Azienda Ospedaliera Universitaria of Modena |
Modena |
Italy |
|
| Fondazione Policlinico Universitario A. Gemelli |
Roma |
Italy |
|
| Azienda Ospedaliera Universitaria Integrata Verona |
Verona |
Italy |
|
| University Clinical Centre in Gdansk |
Gdansk |
Poland |
|
| Barlicki University Hospital |
Lodz |
Poland |
|
| Institute of Tuberculosis and Lung Diseases in Warsaw |
Warsaw |
Poland |
|
| Policlinica Barcelona |
Barcelona |
Spain |
|
| Hospital Universitario Clínic de Barcelona |
Barcelona |
Spain |
|
| L'Hospital Universitari de Bellvitge |
Barcelona |
Spain |
|
| Hospital Universitario La Paz |
Madrid |
Spain |
|
| Hospital Universitario Central de Asturias |
Oviedo |
Spain |
|
| Hospital Universitario Marqués de Valdecilla |
Santander |
Spain |
|
| Hospital Clínico Universitario de Santiago de Compostela |
Santiago de Compostela |
Spain |
|
| University Hospital of Geneve |
Geneva |
Switzerland |
|
| Belfast City Hospital |
Belfast |
United Kingdom |
|
| Queen Elizabeth Hospital |
Birmingham |
United Kingdom |
|
| Royal Papworth Hospital NHSFT |
Cambridge |
United Kingdom |
|
| Royal Infirmary of Edinburgh |
Edinburgh |
United Kingdom |
|
| Guy's Hospital |
London |
United Kingdom |
|
| Royal Brompton Hospital |
London |
United Kingdom |
|
| Altnagelvin Area Hospital |
Londonderry |
United Kingdom |
|
| Churchill Hospital, Oxford University Hospitals NHS Trust |
Oxford |
United Kingdom |
|