Assess the Safety, Pharmacokinetics, Pharmacodynamics and Clinical Activity of RXC007 in Idiopathic Pulmonary Fibrosis

NCT05570058 | Active Not Recruiting Phase 2 FDA Drug

• 1 other identifier: RXC007/0002
• Study Type: interventional
• Target: 48
• Locations: 8 countries
• Sites: 31

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.

Conditions

IPF; Fibrosis

Keywords

Lung; Respiratory; Fibrosis; IPF

Outcome Measures

Primary Outcomes (4)

• Incidence and severity of AEs and SAEs Changes in safety laboratory parameters, vital signs, and ECGs

  The primary endpoints of the study include the incidence and severity of AEs and SAEs

  From Day 1 to post-study follow up visit (12 weeks)

• 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.

  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

  From Day 1 to post-study follow up visit (12 weeks)

• 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

  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

  From Day 1 to post-study follow up visit (12 weeks)

• 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.

  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

  From Day 1 to post-study follow up visit (12 weeks)

Secondary Outcomes (11)

• Pharmacokinetic Parameters - Maximum plasma concentration (Cmax)

  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.

• Minimum observed plasma concentration (Cmin)

  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.

• Pharmacokinetic Parameters - Time to maximum observed concentration (Tmax)

  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.

• Pharmacokinetic Parameters - Terminal elimination half-life (t1/2)

  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.

• Pharmacokinetic Parameters - Elimination rate constant (λz)

  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.

Study Arms (3)

Cohort 1

EXPERIMENTAL

12:4 (RXC007 : Placebo) Dose level 1: 12 weeks (84 days) dosing

Drug: RXC007; Drug: Placebo

Cohort 2

EXPERIMENTAL

12:4 (RXC007 : Placebo) Dose level 2: 12 weeks (84 days) dosing

Drug: RXC007; Drug: Placebo

Expansion Cohort

EXPERIMENTAL

12:4 (RXC007 : Placebo) Dose level 3: 12 weeks (84 days) dosing

Drug: RXC007; Drug: Placebo

Interventions

RXC007 DRUG

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.

Cohort 1; Cohort 2; Expansion Cohort

Placebo DRUG

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

Cohort 1; Cohort 2; Expansion Cohort

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• \. 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.
• 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)

Sponsors & Collaborators

• Redx Pharma Ltd: lead
• Simbec-Orion Group: collaborator

Study Sites (31)

Medical University of Vienna

Vienna, 1090, Austria

Location

E PNE UZ Leuven

Leuven, 3000, Belgium

Location

CHU De Liège

Liège, 4000, Belgium

Location

Pneumologicka klinika 1.LF UK a

Prague, 140 59, Czechia

Location

Azienda Ospedaliero-Universitaria "Ospedali-Riuniti" di Ancona

Ancona, 60126, Italy

Location

Azienda Ospedaliero Universitaria Policlinico ''G.Rodolico-San Marco''

Catania, 95123, Italy

Location

Colonello D'avanzo Hospital

Foggia, 71122, Italy

Location

PO Vito Fazzi

Lecce, 73100, Italy

Location

Ospedale S. Giuseppe Milano

Milan, 20123, Italy

Location

Azienda Ospedaliera Universitaria of Modena

Modena, 41124, Italy

Location

Fondazione Policlinico Universitario A. Gemelli

Roma, 00168, Italy

Location

Azienda Ospedaliera Universitaria Integrata Verona

Verona, 37126, Italy

Location

University Clinical Centre in Gdansk

Gdansk, 01-138, Poland

Location

Barlicki University Hospital

Lodz, Poland

Location

Institute of Tuberculosis and Lung Diseases in Warsaw

Warsaw, 01-138, Poland

Location

Policlinica Barcelona

Barcelona, 08006, Spain

Location

Hospital Universitario Clínic de Barcelona

Barcelona, 08036, Spain

Location

L'Hospital Universitari de Bellvitge

Barcelona, 08907, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital Universitario Central de Asturias

Oviedo, 33011, Spain

Location

Hospital Universitario Marqués de Valdecilla

Santander, 39008, Spain

Location

Hospital Clínico Universitario de Santiago de Compostela

Santiago de Compostela, 15706, Spain

Location

University Hospital of Geneve

Geneva, Switzerland

Location

Belfast City Hospital

Belfast, BT97AB, United Kingdom

Location

Queen Elizabeth Hospital

Birmingham, B15 2GW, United Kingdom

Location

Royal Papworth Hospital NHSFT

Cambridge, CB2 0AY, United Kingdom

Location

Royal Infirmary of Edinburgh

Edinburgh, EH16 4SA, United Kingdom

Location

Guy's Hospital

London, SE1 9RT, United Kingdom

Location

Royal Brompton Hospital

London, SW3 6HP, United Kingdom

Location

Altnagelvin Area Hospital

Londonderry, BT476SB, United Kingdom

Location

Churchill Hospital, Oxford University Hospitals NHS Trust

Oxford, OX7 3LE, United Kingdom

Location

MeSH Terms

Conditions

Fibrosis

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Philip Molyneaux, MD

  Royal Brompton & Harefield NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

• Toby Maher, MD

  University of Southern California, USA

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 28, 2022
• First Posted: October 6, 2022
• Study Start: September 8, 2022
• Primary Completion: June 25, 2024
• Study Completion: January 9, 2025
• Last Updated: August 23, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

PL (3); CZ (1); ES (7); IT (8); CH (1); GB (8); AU (1); BE (2)