A study to investigate the safety, tolerability, and potential effect of RXC007 in patients with idiopathic pulmonary fibrosis
| ISRCTN | ISRCTN60385283 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN60385283 |
| EudraCT/CTIS number | 2022-000498-15 |
| IRAS number | 1005138 |
| Secondary identifying numbers | RXC007/0002, IRAS 1005138, CPMS 51888 |
- Submission date
- 23/04/2022
- Registration date
- 04/05/2022
- Last edited
- 10/05/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Respiratory
Plain English Summary
Background and study aims
The aim of this study is to investigate the study drug RXC007. The main objectives of this study are as follows:
1. To determine the safety and tolerability (the degree to which side effects of a drug can be tolerated) of RXC007 when it is administered as twice-daily doses over a period of up to 12 weeks (84 days).
2. To investigate the levels of RXC007 in the blood, how this changes over a period of time and to evaluate whether there are differences in the levels between different dose strengths of RXC007.
3. To investigate the effect of RXC007 on the body (known as pharmacodynamics) by analysing the levels of certain biomarkers in the body and to assess the effect of RXC007 on markers associated with idiopathic pulmonary fibrosis (IPF).
Who can participate?
A total of up to 64 patients aged between 40 and 80 years of age with idiopathic pulmonary fibrosis (IPF).
What does the study involve?
This study will comprise three main study groups and two additional sub-study groups. The main study will consist of three planned groups of 16 patients with IPF: each group investigating a different dose strength of RXC007 starting at the lowest planned dose in Group 1 to the highest planned dose in Group 3. The sub-study will consist of two groups of up to 8 patients with IPF (each group respectively evaluating the same dose of RXC007 as evaluated in Group 1 and 3 of the main study). The sub-study groups will include evaluations of the levels of RXC007 found in fluid collected from the lungs.
What are the possible benefits and risks of participating?
It is not known for certain that patients will have any clinical benefit by taking part in the trial although, it is intended that the treatment may provide some benefit. However, this cannot be guaranteed. The information from this study may help to treat future patients with IPF.
Possible risks include the following:
The purpose of the data generated in this study is to provide further information and guidance to support the study sponsor in the development of the study drug RXC007 and to provide early data as to the potential effectiveness of RXC007 as a treatment for IPF.
Blood Sampling:
The procedure for blood collection either by direct venepuncture or indwelling cannula may cause mild pain and bruising at the collection site. The placement of an indwelling catheter is proposed in order to minimise these effects for rapid PK sampling. Very rarely, a blockage of a vein or a small nerve injury can occur, resulting in numbness and pain. If this occurs, it will resolve with time.
Blood Pressure & Heart Rate:
The patients' blood pressure and pulse will be measured using an inflatable cuff which will be placed on the arm. They may experience mild discomfort in the arm whilst the cuff is inflated. Small sticky pads will be placed on the patients’ upper body before the ECG. Before the pads are applied, the skin needs to be cleaned. Like Elastoplast®, these sticky pads may be uncomfortable to remove.
COVID-19 Risks:
Patients should also be aware of the risks of exposure to COVID-19. Patients will be required to follow any COVID restrictions and requirements that may be in effect nationally, regionally or in the respective hospital sites. This may include the wearing of masks and COVID-19 testing. Patients will be required to follow all current applicable self-isolation guidelines in the event of a positive COVID-19 test, which may impact their eligibility to continue in the study.
Contraception:
For women of childbearing potential, any patient who is pregnant, breastfeeding or intending to become pregnant will not be eligible for participation. For women of childbearing potential, patients must agree to use two highly effective forms of contraception with their partner using a condom (if applicable) during the study and for at least 3 months following the last dose of study medication.
For males with partners of childbearing potential, patients must not father a child during this study or for a safety period of 3 months following the last dose of study medication. Patients must agree to use two highly effective forms of contraception with their partner using a condom (if applicable) during the study and for at least 3 months following the last dose of study medication. Males who have been sterilised or engage in non-vaginal intercourse should use a condom to prevent exposure of semen to any partner (male or female) until 3 months following the last dose of study medication. Patients must not donate sperm until 3 months following the last dose of study medication.
Spirometry & DLCO:
Performing the lung function and breathing tests may cause some coughing, shortness of breath and lightheadedness. As part of the lung function testing, patients will be required to undergo a lung diffusion test which will measure how well their lungs allow oxygen and carbon dioxide to pass in and out of the blood. For this test, patients may be required to sit in a small chamber known as a body box.
This is a small, confined space (roughly the same size as a standard toilet cubicle) and therefore, patients may feel claustrophobic during the conduct of this test. The test may take up to 30-45 minutes to complete and patients should notify the staff at any time if they start to feel claustrophobic and the test may be stopped.
CT Scan:
Patients will have a CT scan of the chest on a minimum of 4 occasions (2 scans per timepoint). These procedures use ionising radiation to form images of your body and provide your doctor with other clinical information. The level of radiation exposure per scan is approximately 9.7 milli-Sieverts (mSv) which is a measure of radiation dose). In comparison, a skull X-ray is 0.07 mSv, a chest X-ray is 0.014 mSv and a transatlantic flight is equivalent to 0.08 mSv. The UK average annual dose of ionising radiation exposure from all sources (i.e., natural and man-made) is 2.7 mSv (which goes up to 7.4 mSv for people living in Cornwall). Therefore, the exposure in this study is equivalent to around 2.5 years of background radiation per scan. The risks associated with this have been thoroughly assessed by medical radiation experts and it has been determined that the radiation exposure in this study poses minimal risk.
Bronchoscopy:
As part of the sub-study, participants will be required to undergo a bronchoscopy on two occasions. The procedure itself may cause some discomfort as the bronchoscope is passed through into the lungs but this should resolve once the scope is fully in place. The procedure may take up to 45 minutes to complete. Following the procedure, patients may experience a cough, sore throat, voice loss, and/or fever. The bronchoalveolar lavage procedure will be carried out under full medical supervision and every effort will be made to minimise any imposed risk to patients.
Where is the study run from?
The study will be conducted at several hospital sites across the United Kingdom and Europe.
When is the study starting and how long is it expected to run for?
December 2021 to November 2024
Who is funding the study?
This study is funded and sponsored by a pharmaceutical company called Redx Pharma Plc, based and headquartered in the United Kingdom (UK)
Who is the main contact?
Dr Helen Timmis, Senior Medical Director, Redx Pharma Plc
Contact information
Scientific
Redx Pharma Plc
Block 33
Mereside
Alderley Park
Cheshire
SK10 4TG
United Kingdom
 ORCID ID |
0000-0001-6793-3698 |
|---|---|
| Phone | +44 (0) 7854 608 784 |
| h.timmis@redxpharma.com |
Public
Redx Pharma Plc
Block 33
Mereside
Alderley Park
Cheshire
SK10 4TG
United Kingdom
| ORCID ID |
0000-0001-6793-3698 |
|---|---|
| Phone | +44 (0)7854 608 784 |
| h.timmis@redxpharma.com |
Principal Investigator
Royal Brompton Hospital
Sydney St
London
SW3 6NP
United Kingdom
| Phone | +44 (0)20 7352 8121 |
|---|---|
| p.molyneaux@imperial.ac.uk |
Study information
| Study design | Open randomized placebo-controlled double-blind trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use contact details to request a participant information sheet. |
| Scientific title | A multi-cohort, randomised, placebo-controlled Phase IIa study to assess the safety, pharmacokinetics, pharmacodynamics and clinical activity of ascending doses of RXC007 in patients with idiopathic pulmonary fibrosis |
| Study acronym | RXC007/0002 |
| Study hypothesis | The primary objective of the study is: 1. To assess the safety and tolerability of RXC007 when given for 12 weeks (84 days), alone and in combination with nintedanib or pirfenidone The secondary objectives of the study are: 1. To assess the pharmacokinetic (PK) profile of: 1.1. RXC007, alone and in combination with nintedanib or pirfenidone. 1.2. Nintedanib and pirfenidone at baseline and at steady state in combination with RXC007. 2. To assess the potential of RXC007 to demonstrate clinical activity in patients with idiopathic pulmonary fibrosis (IPF) |
| Ethics approval(s) | Approved 14/06/2022, Wales Research Ethics Committee 2 (Health and Care Research Wales, Castlebridge 4, 15-19 Cowbridge Road East, Cardiff, CF11 9AB, UK; Wales.REC2@wales.nhs.uk), ref: 22/WA/0122 |
| Condition | Idiopathic pulmonary fibrosis (IPF) |
| Intervention | 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-study. The study cohorts will comprise the following: Main Study Cohorts Cohort 1 Dose Level 1: 20 mg twice daily Randomised, double-blind, placebo-controlled 12 weeks (84 days) dosing, comprised of 3 cycles of 28 days, with a safety review by the Dose Review Committee (DRC) when the first 8 patients in Cohort 1 have had 28 days of study treatment. 16 patients, comprising 12 patients randomised to receive RXC007 and 4 patients randomised to receive placebo, to include: 1. At least 4 patients who are not on any IPF treatment 2. At least 4 patients who are receiving nintedanib 3. At least 4 patients who are receiving pirfenidone Cohort 2 Dose Level 2: 50 mg twice daily Randomised, double-blind, placebo-controlled 12 weeks (84 days) dosing, comprised of 3 cycles of 28 days* Cohort 2 may open when 16 patients have been randomised and 8 evaluable patients have completed a minimum of 28 days’ dosing in Cohort 1, including a minimum of 4 patients on no background IPF therapy and following a safety review by the DRC. 16 patients, comprising 12 patients randomised to receive RXC007 and 4 patients randomised to receive placebo, to include: 1. At least 4 patients who are not on any IPF treatment 2. At least 4 patients who are receiving nintedanib 3. At least 4 patients who are receiving pirfenidone Cohort 3 Dose Level 3: 70 mg twice daily Randomised, double-blind, placebo-controlled 12 weeks (84 days) dosing, comprised of 3 cycles of 28 days Cohort 3 will open when 16 patients have been randomised and 8 evaluable patients have completed a minimum of 28 days dosing in Cohort 2 and following a safety review by the DRC. 16 patients, comprising 12 patients randomised to receive RXC007 and 4 patients randomised to receive placebo, to include: 1. At least 4 patients who are not on any IPF treatment 2. At least 4 patients who are receiving nintedanib 3. At least 4 patients who are receiving pirfenidone BAL-Fluid Translational Science Sub Study Cohorts Cohort 1B Dose Level 1: 20 mg twice daily 28 days dosing with an option to continue for 84 days Cohort 3B Dose Level 3: 70 mg twice daily 28 days dosing with an option to continue for 84 days* The dose will be the same as Cohort 3 in the main study and may open when the corresponding main study cohort opens. 4-8 patients, comprising 3-6 patients randomised to receive RXC007 and 1 2 patients randomised to receive placebo, all of whom are on no treatment for IPF. Cohort 1B data will be reviewed after 4 patients and if no biomarker changes are demonstrated, no additional patients will be enrolled at this dose level and the next 4 patients may be assigned to the Cohort 2 dose, once Cohort 2 is open. *At 12 weeks, at the investigator's discretion and following discussion with the sponsor, patients may be offered RXC0007 treatment beyond Day 84, up to a maximum of 12 weeks after Day 84. Before continuing dosing, patients should discuss any potential alternative treatments with the trial investigator and sign an informed consent form. The study will consist of the following study visits: Screening period: Day (D) -28 to D -1 Treatment period: Cycle (C)1D1 (no time window) C1D8 (±3 days) C1D15 (±3 days) C1D22 (±3 days) C2D1 (±3 days) C2D15 (±3 days) C3D1 (±3 days) C3D15 (±3 days) C3D28 - End of Treatment (EOT) (±3 days) Post-treatment period: Follow-up (FU)/End of Study (EOS): 30 days after the last dose (-3 days to +7 days) Overall study duration (for each patient): an approximate study duration of 142 days The study end is defined as last subject last visit. The study will take place across several sites within the UK, EU and USA. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | RXC007 |
| Primary outcome measure | 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 outcome measures | 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, λz, AUC0-∞, 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) |
| Overall study start date | 02/12/2021 |
| Overall study end date | 06/11/2024 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 40 Years |
| Upper age limit | 80 Years |
| Sex | Both |
| Target number of participants | 64 |
| Participant 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) <2x upper limit of normal (ULN). Total bilirubin <1.5 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, 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. |
| Participant 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. 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 |
| Recruitment start date | 29/06/2022 |
| Recruitment end date | 29/06/2024 |
Locations
Countries of recruitment
- Belgium
- Czech Republic
- England
- France
- Germany
- Italy
- United Kingdom
- United States of America
Study participating centres
London
SW3 6NP
United Kingdom
London
SE1 9RS
United Kingdom
Edgbaston
Birmingham
B15 2WB
United Kingdom
Barrack Road
Exeter
EX2 5DW
United Kingdom
Fazakerley
Liverpool
L9 7AL
United Kingdom
Edinburgh
EH16 4TJ
United Kingdom
Trumpington
Cambridge
CB2 0AY
United Kingdom
Southampton
SO16 6YD
United Kingdom
Old Road
Headington
Oxford
OX3 7LE
United Kingdom
Sponsor information
Industry
Block 33
Mereside
Alderley Park
Cheshire
SK10 4TG
England
United Kingdom
| Phone | +44 (0)7854 608 784 |
|---|---|
| h.timmis@redxpharma.com | |
| Website | https://www.redxpharma.com/ |
"ROR" |
https://ror.org/04wysdg63 |
Funders
Funder type
Industry
No information available
Results and Publications
| Intention to publish date | 06/05/2025 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | 1. Internal report 2. Submission to regulatory authorities |
| IPD sharing plan | The study data will be shared with relevant research groups and external stakeholders collaborating with the study sponsor to support the future development of the IMP within the boundaries of strict confidentiality agreements. The data-sharing plans for the current study are unknown and will be made available at a later date. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
10/05/2024: The following changes were made to the study record:
1. The recruitment end date was changed from 29/06/2022 to 29/06/2024.
2. The overall study end date was changed from 06/05/2024 to 06/11/2024.
3. Ethics approval details added.
07/06/2022: Internal review.
25/04/2022: Trial's existence confirmed by the HRA.
