Clinical trial NCT05570058: Assess the Safety, Pharmacokinetics, Pharmacodynamics and Clinical Activity of RXC007 in Idiopathic Pulmonary Fibrosis
Official title: A Multi-Cohort, Randomised, Placebo-Controlled Phase 2a Study to Assess the Safety, Pharmacokinetics, Pharmacodynamics and Clinical Activity of Ascending Doses of RXC007 in Patients With Idiopathic Pulmonary Fibrosis
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: IPF
Fibrosis
Keywords: Lung
Respiratory
Fibrosis
IPF
Lead sponsor: Redx Pharma Ltd
Sponsor class: INDUSTRY
Collaborators: name: Simbec-Orion Group
First posted: 2022-10-06
Enrollment: 48
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief 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.

Detailed description: The purpose of this study is to investigate the study drug RXC007.

The main objectives of this study are as follows:

* To determine the safety and tolerability (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).
* To investigate the concentration of RXC007 (how much drug is in your blood), how this changes over a period of time and to evaluate whether there are differences in the concentration between different dose strengths of RXC007.
* 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). Biomarkers are markers within the body such as a molecule or compound made by cells in the body, which can be measured and used to identify a particular disease.

Eligibility criteria: 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 outcomes:
measure: Incidence and severity of AEs and SAEs Changes in safety laboratory parameters, vital signs, and ECGs
timeFrame: From Day 1 to post-study follow up visit (12 weeks)
measure: 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.
timeFrame: From Day 1 to post-study follow up visit (12 weeks)
measure: 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
timeFrame: From Day 1 to post-study follow up visit (12 weeks)
measure: 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.
timeFrame: From Day 1 to post-study follow up visit (12 weeks)
Secondary outcomes:
measure: Pharmacokinetic Parameters - Maximum plasma concentration (Cmax)
timeFrame: For Cycle1 Day1 pre-dose, 1, 2, 3, 4, 8 h post-dose. For Cycle1 Day8 pre-dose, 1, 2, 3, 4, 8 h post-dose for all BID schedules. If the schedule is changed to QD, for Cycle1 Day8 will include a 24 h post-dose sample (Cycle1 Day9). On Cycle2 Day1 pre-dose.
measure: Minimum observed plasma concentration (Cmin)
timeFrame: For Cycle1 Day1 pre-dose, 1, 2, 3, 4, 8 h post-dose. For Cycle1 Day8 pre-dose, 1, 2, 3, 4, 8 h post-dose for all BID schedules. If the schedule is changed to QD, for Cycle1 Day8 will include a 24 h post-dose sample (Cycle1 Day9). On Cycle2 Day1 pre-dose.
measure: Pharmacokinetic Parameters - Time to maximum observed concentration (Tmax)
timeFrame: For Cycle1 Day1 pre-dose, 1, 2, 3, 4, 8 h post-dose. For Cycle1 Day8 pre-dose, 1, 2, 3, 4, 8 h post-dose for all BID schedules. If the schedule is changed to QD, for Cycle1 Day8 will include a 24 h post-dose sample (Cycle1 Day9). On Cycle2 Day1 pre-dose.
measure: Pharmacokinetic Parameters - Terminal elimination half-life (t1/2)
timeFrame: For Cycle1 Day1 pre-dose, 1, 2, 3, 4, 8 h post-dose. For Cycle1 Day8 pre-dose, 1, 2, 3, 4, 8 h post-dose for all BID schedules. If the schedule is changed to QD, for Cycle1 Day8 will include a 24 h post-dose sample (Cycle1 Day9). On Cycle2 Day1 pre-dose.
measure: Pharmacokinetic Parameters - Elimination rate constant (λz)
timeFrame: For Cycle1 Day1 pre-dose, 1, 2, 3, 4, 8 h post-dose. For Cycle1 Day8 pre-dose, 1, 2, 3, 4, 8 h post-dose for all BID schedules. If the schedule is changed to QD, for Cycle1 Day8 will include a 24 h post-dose sample (Cycle1 Day9). On Cycle2 Day1 pre-dose.
measure: Pharmacokinetic Parameters - Area under the concentration-time curve (AUC) extrapolated to infinity (AUC0-inf)
timeFrame: For Cycle1 Day1 pre-dose, 1, 2, 3, 4, 8 h post-dose. For Cycle1 Day8 pre-dose, 1, 2, 3, 4, 8 h post-dose for all BID schedules. If the schedule is changed to QD, for Cycle1 Day8 will include a 24 h post-dose sample (Cycle1 Day9). On Cycle2 Day1 pre-dose.
measure: Pharmacokinetic Parameters - Total apparent clearance following extravascular administration (CL/F)
timeFrame: For Cycle1 Day1 pre-dose, 1, 2, 3, 4, 8 h post-dose. For Cycle1 Day8 pre-dose, 1, 2, 3, 4, 8 h post-dose for all BID schedules. If the schedule is changed to QD, for Cycle1 Day8 will include a 24 h post-dose sample (Cycle1 Day9). On Cycle2 Day1 pre-dose.
measure: Pharmacokinetic Parameters - Apparent volume of distribution following extravascular administration (Vz/F)
timeFrame: For Cycle1 Day1 pre-dose, 1, 2, 3, 4, 8 h post-dose. For Cycle1 Day8 pre-dose, 1, 2, 3, 4, 8 h post-dose for all BID schedules. If the schedule is changed to QD, for Cycle1 Day8 will include a 24 h post-dose sample (Cycle1 Day9). On Cycle2 Day1 pre-dose.
measure: Pharmacokinetic Parameters - Area under the plasma concentration-time curve during a dosing interval at steady state (AUCss)
timeFrame: For Cycle1 Day1 pre-dose, 1, 2, 3, 4, 8 h post-dose. For Cycle1 Day8 pre-dose, 1, 2, 3, 4, 8 h post-dose for all BID schedules. If the schedule is changed to QD, for Cycle1 Day8 will include a 24 h post-dose sample (Cycle1 Day9). On Cycle2 Day1 pre-dose.
measure: % predicted and absolute volume change from baseline in Forced Vital Capacity (FVC) at 12 weeks [central review]
timeFrame: At Screening (Day28 to Day-1), Cycle1 Day1 pre-dose and post-dose, Cycle1 Day8, Cycle1 Day15, Cycle1 Day22, Cycle2 Day1(The day after Cycle1 Day28), Cycle2 Day15, Cycle3 Day1, Cycle3 Day28, End Of Treatment: last day of the dosing Day 21
measure: % predicted and absolute change from baseline in carbon monoxide diffusion capacity (DLCO)
timeFrame: At Screening (day28 to Day-1), Cycle1 Day1 pre-dose, Cycle1 Day15, Cycle2 Day1 (The day after Cycle1 Day28)
Other outcomes:
Locations:
city: Wien
country: Austria
facility: Medical University of Vienna
city: Leuven
country: Belgium
facility: E PNE UZ Leuven
city: Liège
country: Belgium
facility: CHU De Liège
city: Praha
country: Czechia
facility: Pneumologicka klinika 1.LF UK a
city: Ancona
country: Italy
facility: Azienda Ospedaliero-Universitaria "Ospedali-Riuniti" di Ancona
city: Catania
country: Italy
facility: Azienda Ospedaliero Universitaria Policlinico ''G.Rodolico-San Marco''
city: Foggia
country: Italy
facility: Colonello D'avanzo Hospital
city: Lecce
country: Italy
facility: PO Vito Fazzi
city: Milan
country: Italy
facility: Ospedale S. Giuseppe Milano
city: Modena
country: Italy
facility: Azienda Ospedaliera Universitaria of Modena
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario A. Gemelli
city: Verona
country: Italy
facility: Azienda Ospedaliera Universitaria Integrata Verona
city: Gdansk
country: Poland
facility: University Clinical Centre in Gdansk
city: Lodz
country: Poland
facility: Barlicki University Hospital
city: Warsaw
country: Poland
facility: Institute of Tuberculosis and Lung Diseases in Warsaw
city: Barcelona
country: Spain
facility: Policlinica Barcelona
city: Barcelona
country: Spain
facility: Hospital Universitario Clínic de Barcelona
city: Barcelona
country: Spain
facility: L'Hospital Universitari de Bellvitge
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Oviedo
country: Spain
facility: Hospital Universitario Central de Asturias
city: Santander
country: Spain
facility: Hospital Universitario Marqués de Valdecilla
city: Santiago De Compostela
country: Spain
facility: Hospital Clínico Universitario de Santiago de Compostela
city: Geneva
country: Switzerland
facility: University Hospital of Geneve
city: Belfast
country: United Kingdom
facility: Belfast City Hospital
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital
city: Cambridge
country: United Kingdom
facility: Royal Papworth Hospital NHSFT
city: Edinburgh
country: United Kingdom
facility: Royal Infirmary of Edinburgh
city: Londonderry
country: United Kingdom
facility: Altnagelvin Area Hospital
city: London
country: United Kingdom
facility: Guy's Hospital
city: London
country: United Kingdom
facility: Royal Brompton Hospital
city: Oxford
country: United Kingdom
facility: Churchill Hospital, Oxford University Hospitals NHS Trust
Study officials:
affiliation: Royal Brompton & Harefield NHS Foundation Trust
name: Philip Molyneaux, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Southern California, USA
name: Toby Maher, MD
role: PRINCIPAL_INVESTIGATOR
References: