Idiopathic pulmonary fibrosis (IPF) Respiratory Other interstitial pulmonary diseases with fibrosis
Conditions
Interventions
Approximately 48 patients will be enrolled in three sequential cohorts in the main study and 16 evaluable patients will be enrolled in two sequential cohorts in a parallel translational science sub-st
Sponsors
Redx Pharma (United Kingdom)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Ability to provide signed and dated informed consent 2. Aged =40 to 80 years at the time of signing the informed consent 3. Diagnosis of IPF within 5 years of Screening based on the modified IPF guidelines for diagnosis and management of IPF and confirmed on independent central imaging review 4. Combination of HRCT pattern, as assessed by central reviewers, consistent with diagnosis of IPF 5. FVC % predicted =50% predicted of normal at Screening, with no clinically significant deterioration between the Screening Visit and randomisation, as determined by the Investigator 6. DLco (Hb-adjusted) at screening =30% 7. 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 8. 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 9. No clinically significant history of previous allergy/ sensitivity to RXC007 or any of the excipients contained within the Investigational Medicinal Product (IMP) 10. Blood cell parameters within the following limits: 10.1. Haemoglobin >10 g/dL 10.2. WBC count >3.00 × 10³/µL 10.3. Neutrophils >1.50 × 10³/µL 10.4. Platelets >80 × 10³/µL 11. Alanine transaminase (ALT) and aspartate transaminase (AST) 470 ms. 14. 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. 15. Patients must be willing to comply with institutional COVID-19 testing policy. 16. Female patients must be surgically sterile, post-menopausal (minimum 1 year without menses), or agree to use two or more of the following forms of highly effective contraception with all male sexual partners from the time of signing the Patient Informed Consent Document (PICD) until 3 months after the last dose of study medication: hormonal (i.e., oral, transdermal, implant, or injection); intrauterine device (IUD), Intrauterine system (IUS) (e.g., Mirena), or bilateral tubal occlusion; vasectomised partner (with appropriate post-vasectomy documentation of the absence of sperm in the ejaculate); or abstinence. 17. Men must use a condom (with spermicide) during the study, and for 3 months after the last dose of study drug, with all sexual partners. Men must not donate sperm for 3 months after the last dose of study drug. Additional Inclusion Criteria for the Translational Science Sub Study only: 18. Patients must be considered fit to undergo two bronchoscopies, in the opinion of the Investigator.
Exclusion criteria
Exclusion criteria: 1. Currently receiving or planning to initiate treatment for IPF with agents not approved for that indication 2. FEV1/FVC ratio 15 hours/day 6. Acute IPF exacerbation within 6 months of Screening or during Screening 7. History of ongoing malignant disease, including solid tumours and hematologic malignancies, with the exception of basal cell carcinoma, squamous-cell carcinoma, and carcinoma in situ of the cervix that have been completely excised and considered cured >2 years prior to Screening 8. Significant cardiac disease (e.g., New York Heart Association Class 3 or 4; myocardial infarction within the past 6 months; unstable angina; coronary angioplasty or coronary artery bypass graft within the past 6 months; uncontrolled atrial or ventricular cardiac arrhythmias; or pulmonary hypertension requiring pharmacologic treatment) 9. 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. Note: Serological testing is not needed if not clinically indicated 10. Creatinine clearance <60 mL/min according to Cockcroft Gault equation 11. A clinically significant history of GI disorder likely to influence IMP absorption 12. A clinically significant history of infection in the last 3 months 13. Evidence of renal, hepatic, central nervous system, respiratory, cardiovascular, or metabolic dysfunction 14. A clinically significant history of drug or alcohol abuse within the past 3 months prior to Screening 15. Disease other than IPF with a life expectancy of less than 12 weeks 16. Inability to communicate well with the Investigators (i.e., language problem, poor mental development, or impaired cerebral function) 17. Participation in a New chemical entity (NCE) clinical study within the previous 3 months or five half-lives, whichever is longer, or a marketed drug clinical study within the 30 days or five half-lives, whichever is longer 18. Female who is pregnant or breastfeeding 19. Patients who are currently receiving prohibited medications and are unable to stop 20. Patients who are currently receiving steroids or formal anticoagulants (antiplatelet agents are permitted) and are unable to stop 21. Participants who have received a COVID-19 vaccine injection within 72 hours prior to the first dose of IMP Additional exclusion criteria for the Translational Science Sub Study: 22. Participants with any contra-indication to bronchoscopy and alveolar lavage including tracheal stenosis, pulmonary hypertension, severe hypoxia, or hypercapnia 23. Patients in the sub study are not permitted to receive nintedanib or pirfenidone within 3 weeks of randomisation and throughout the Treatment period
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. The incidence and severity of AEs and serious adverse events (SAEs) recorded from the time of signature of informed consent until 30 days after the last of RXC007/placebo 2. Changes in safety laboratory parameters, vital signs, and ECGs: 2.1. Laboratory safety testing: Main Study: Screening, Cycle 1: Days 1, 8, 15, 22, Cycles 2 & 3: Days 1, 15 & 28 (Cycle 3 only) & Follow Up Extended: Cycles 1-3: Day 1 & 15 2.2. Vital signs (blood pressure, heart rate, respiration rate and oral temperature) will be measured at the following timepoints: Main Study: Screening, Cycle 1: Days 1, 8, 15, 22, Cycles 2 & 3: Days 1, 15 & 28 (Cycle 3 only) & Follow Up Extended: Cycles 1-3: Day 1 & 15 2.3. ECG (in triplicate): 12-lead ECGs will be measured in triplicate at the following timepoints: Main Study: Screening, Cycle 1: Days 1, 8, 15, 22, Cycles 2 & 3: Day 1, Day 28 (Cycle 3 only) & Follow Up Extended: Cycles 1-3: Day 1 All timepoints for assessments are pre-dose timepoints (relative to the morning dose of RXC007) | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Derived PK parameters calculated from measurement of plasma concentrations of RXC007, nintedanib and pirfenidone: maximum plasma concentration (Cmax) after Dose 1, Cmax at steady state, minimum observed plasma concentration (Cmin) at steady state as well as other relevant parameters (e.g., tmax, t½, ?z, AUC0-8, CL/F, Vz/F, Css, AUCss). Plasma samples for measurement of concentrations as described above will be obtained at the following timepoints: Main Study Dosing Cycle 1: Days 1 & 8 (pre-dose, 1, 2, 3, 4, 8 h post-dose), Dosing Cycle 2: Day 1 Extended Dosing: Cycles 1-3: Day 1 2. Efficacy parameters derived from measured outcomes of lung function testing (spirometry and carbon monoxide diffusion capacity (DLCO): 2.1. % predicted and absolute volume change from baseline in FVC at 12 weeks (central review) 2.2. % predicted and absolute change from baseline in DLCO at 12 weeks Assessment of lung function using spirometry will be conducted at the following timepoints: Main Study Dosing Cycle 1: Days 1, 8, 15, 22 (pre-dose relative to morning dose of RXC007) Main Study Dosing Cycle 2: Days 1 & 15 (pre-dose relative to morning dose of RXC007) Main Study Dosing Cycle 3: Days 1, 15 & 28 (pre-dose relative to morning dose of RXC007) Extended: Cycles 1-3: Days 1 & 15 (pre-dose relative to morning dose of RXC007) Assessment of lung function using DLCO will be conducted at the following timepoints:: Dosing Cycle 1: Days 1 & 15 (pre-dose relative to morning dose of RXC007) Dosing Cycle 2: Day 1 (pre-dose relative to morning dose of RXC007) Dosing Cycle 3: Day 28 (pre-dose relative to morning dose of RXC007) Extended: Cycles 1-3: Day 1 (pre-dose relative to morning dose of RXC007) | — |
Countries
Belgium, Czech Republic, England, France, Germany, Italy, United Kingdom, United States of America
Contacts
Public ContactHelen Timmis
Outcome results
None listed