| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Idiopathic Pulmonary Fibrosis (IPF) |
|
| E.1.1.1 | Medical condition in easily understood language |
| Lung condition associated with fibrosis and inflammation |
|
| E.1.1.2 | Therapeutic area | Body processes [G] - Physiological processes [G07] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10067761 |
| E.1.2 | Term | Exacerbation of idiopathic pulmonary fibrosis |
| E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| - To assess the safety and tolerability of RXC007 when given for 12 weeks (84 days), alone and in combination with nintedanib or pirfenidone. |
|
| E.2.2 | Secondary objectives of the trial |
The secondary objectives of the study are:
- To assess the PK profile of RXC007, alone and in combination with nintedanib or pirfenidone.
- To assess the PK profile of nintedanib and pirfenidone at baseline and at steady state in combination with RXC007.
- To assess the potential of RXC007 to demonstrate clinical activity in patients with IPF.
|
|
| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Translation Science Sub-Study Cohorts - Cohorts 1b and 3b
Up to 2 cohorts of 8 patients each. Dose level will be selected from emerging data from the main study and will not exceed 70mg BID 28 days dosing with an option to continue for 84 days*
Patients in these cohorts will undergo bronchoscopy at baseline and on Cycle 2 Day 1 to align with PK sampling
Objectives are as follows:
- To explore potential biomarker changes in paired samples of bronchial absorption (at selected sites), BAL-derived fluid and cells, and epithelial brushings, obtained at Pre-dose C1D1 and 28 days post-dosing, that may be indicative of target engagement or disease modification.
- To explore feasibility of determination of RXC007 concentration in BAL fluid. |
|
| E.3 | Principal 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:
o Haemoglobin >10 g/dL (>100 g/L)
o WBC count >3.00 × 10^3/μL (>3.00 x 10^9/L)
o Neutrophils >1.50 × 10^3/μL (>1.50 x 10^9/L)
o Platelets >80 × 10^3/μL (>80 x 10^9/L)
11. Alanine transaminase (ALT) and aspartate transaminase (AST) <2x upper limit of normal (ULN). Total bilirubin <1.5x ULN.
12. Negative human immunodeficiency virus (HIV), hepatitis B surface antigen (HbsAg) and hepatitis C virus antibody (HCV Ab) test results at Screening.
13. No clinically significant abnormalities in 12-lead ECG determined within 28 days before first dose of IMP including a QTcF interval >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, (hysterectomy, bilateral salpingectomy or bilateral oophorectomy), post-menopausal (minimum 1 year without menses), or agree to use highly effective contraception with all male sexual partners from the time of signing the Patient Informed Consent Document (PICD) until 6 months after the last dose of study medication: combined (oestrogen and progestogen containing) hormonal contraception associated with the inhibition of ovulation (oral, intravaginal or transdermal); progestogen-only contraception associated with the inhibition of ovulation (oral, 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.*
*Defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the subject.
Note: hormonal contraception should be supplemented by use of a condom/ other barrier method.
17. Men must agree to use a condom (with spermicide) during the study, and for 6 months after the last dose of study drug, with all sexual partners. Male subjects with female partner of child-bearing potential should use an additional form of contraception during the study and for 6 months after last dose of study drug. Men must agree not to donate sperm for 6 months after the last dose of study drug. |
|
| E.4 | Principal exclusion criteria |
1. Currently receiving or planning to initiate treatment for IPF with agents not approved for that indication.
2. FEV1/FVC ratio <0.7 at Screening, pre-bronchodilator use.
3. 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.
5. Need for continuous oxygen supplementation, defined as >15 hours/day.
6. Acute IPF exacerbation within 6 months of Screening or during Screening.
7. Patients who have any history of an active (requiring treatment) malignancy within 2 years of screening (except any in-situ carcinoma, non-melanoma skin carcinoma, and early prostate cancer with a normal prostate-specific antigen [PSA]).
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 which, in the opinion of the investigator, would make the patient unsuitable for inclusion or unable to complete the study.
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 anticoagulants (anti-platelet 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. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
• The incidence and severity of AEs and serious adverse events (SAEs),
• Changes in safety laboratory parameters, vital signs and ECGs.
|
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
AEs & SAEs will be recorded from the time of signature of informed consent until 30 days after the last of RXC007/placebo.
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
Vital Signs
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
ECG (in triplicate)
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). |
|
| E.5.2 | Secondary end point(s) |
The secondary endpoints for this study are:
- Derived PK parameters calculated from measurement of plasma concentrations of RXC007.
- Efficacy parameters derived from measured outcomes of lung function testing (spirometry and carbon monoxide diffusion capacity (DLCO).
Parameters for PK are as follows:
• 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, λz, AUC0-∞, CL/F, Vz/F, Css, AUCss).
Parameters for Lung Function Testing are as follows:
• % predicted and absolute volume change from baseline in FVC at 12 weeks (central review).
• % predicted and absolute change from baseline in DLCO at 12 weeks. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
PK
Main Study Dosing Cycle 1: Days 1 & 8 (pre-dose, 1, 2, 3, 4, 8 hr post dose), Dosing Cycle 2: Day 1
Extended: Cycles 1-3: Day 1
Spirometry
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)
DLCO
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) |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 5 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 27 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| United Kingdom |
| United States |
| Austria |
| Belgium |
| Czechia |
| France |
| Germany |
| Italy |
| Poland |
| Spain |
|
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | |
| E.8.9.1 | In the Member State concerned months | 7 |
| E.8.9.1 | In the Member State concerned days | 15 |
| E.8.9.2 | In all countries concerned by the trial months | 7 |
| E.8.9.2 | In all countries concerned by the trial days | 15 |
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