Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register allows you to search for protocol and results information on:
  • interventional clinical trials that are conducted in the European Union (EU) and the European Economic Area (EEA);
  • clinical trials conducted outside the EU / EEA that are linked to European paediatric-medicine development.
  • Learn   more about the EU Clinical Trials Register   including the source of the information and the legal basis.


    The EU Clinical Trials Register currently displays   42336   clinical trials with a EudraCT protocol, of which   6971   are clinical trials conducted with subjects less than 18 years old.
    The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).


    Phase 1 trials conducted solely in adults and that are not part of an agreed PIP are not public in the EU CTR (refer to European Guidance 2008/C 168/02   Art. 3 par. 2 and   Commission Guideline 2012/C 302/03,   Art. 5) .

    Clinical Trials marked as "Trial now transitioned" were transitioned to the Clinical Trial Regulation 536/2014 and can be further followed in the Clinical Trial Information System  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Print Download

    Summary
    EudraCT Number:2017-000149-30
    Sponsor's Protocol Code Number:Edge92882
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:GB - no longer in EU/EEA
    Date on which this record was first entered in the EudraCT database:2017-09-05
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedUK - MHRA
    A.2EudraCT number2017-000149-30
    A.3Full title of the trial
    A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study of Safety, Tolerability and Efficacy of Pirfenidone in Patients with Rheumatoid Arthritis Interstitial Lung Disease
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study of Safety, Tolerability and Efficacy of Pirfenidone in Patients with Rheumatoid Arthritis Interstitial Lung Disease
    A.3.2Name or abbreviated title of the trial where available
    TRAIL1
    A.4.1Sponsor's protocol code numberEdge92882
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT02808871
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorUniversity Hospitals of Leicester NHS Trust
    B.1.3.4CountryUnited Kingdom
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportGenentech Inc
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationUniversity Hospitals of Leicester NHS Trust
    B.5.2Functional name of contact pointFelix Woodhead
    B.5.3 Address:
    B.5.3.1Street AddressGlenfield Hospital
    B.5.3.2Town/ cityGroby Road
    B.5.3.3Post codeLE3 9QP
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number0116 258 3507
    B.5.6E-mailfelix.woodhead@uhl-tr.nhs.uk
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Esbriet
    D.2.1.1.2Name of the Marketing Authorisation holderRoche Registration Limited
    D.2.1.2Country which granted the Marketing AuthorisationUnited Kingdom
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameEsbriet
    D.3.4Pharmaceutical form Capsule
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNPirfenidone
    D.3.9.1CAS number 53179-13-8
    D.3.9.4EV Substance CodeAS1
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number267
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboCapsule
    D.8.4Route of administration of the placeboOral use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Rheumatoid arthritis associated interstitial lung disease (RA-ILD)
    E.1.1.1Medical condition in easily understood language
    ILD is inflammation and scarring of the lung tissue. In the case of RA-ILD, the scarring is caused when the over-active immune system attacks the lungs causing scarring to build up over time.
    E.1.1.2Therapeutic area Diseases [C] - Respiratory Tract Diseases [C08]
    MedDRA Classification
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    1.To assess the efficacy and safety of pirfenidone 2403 mg/day as compared to placebo in patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD).

    E.2.2Secondary objectives of the trial
    1. To explore the role of peripheral blood biomarkers in predicting disease progression and survival in patients with RA-associated interstitial lung disease.

    2. To explore a spectrum of validated questionnaires to assess disease specific patient reported outcomes including overall health, and perspectives on symptoms, performance and quality of life.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Age 18 through 85 years, inclusive, at Screening
    2. Probable or definite diagnosis of RA according to revised 2010 ACR/EULAR criteria, without evidence or suspicion of an alternative diagnosis that may contribute to their interstitial lung disease.
    3. Diagnosis of ILD
    a. supported by clinically indicated HRCT, and when available surgical lung biopsy (SLB), prior to Screening, and
    b. presence of fibrotic abnormality affecting more than 10% of the lung parenchyma, with or without traction bronchiectasis or honeycombing, on Screening and confirmed by adjudicated HRCT prior to Baseline
    4. Clinical symptoms consistent with ILD (i.e., cough, dyspnea)
    5. No features supporting an alternative diagnosis on transbronchial biopsy, or SLB, if performed prior to Screening
    6. Attainment of the following centralized spirometry criteria (based on local spirometry on standardized equipment and centralized quality controlled):
    a. percent predicted FVC ≥ 40% at Screening
    b. change in pre-bronchodilator FVC (measured in liters) between Screening (Visit 1) and Baseline (Visit 2) must be a <10% relative difference, calculated as:
    100% * [absolute value (Screening FVC – Baseline FVC) / Screening FVC]
    c. percent predicted DLCO ≥30% or TLCO at Screening
    d. Screening (Visit 1) Pre-bronchodilator (BD) and Post-BD spirometry meets ATS quality criteria as determined by a central reviewer.
    d. Screening (Visit 1) Pre-bronchodilator (BD) and Post-BD spirometry meets ATS quality criteria as determined by a central reviewer.
    e. Baseline (Visit 2) Pre-BD spirometry meets ATS quality criteria as determined by either a site Investigator or the central reviewer.


    7. Stable dose (at least three months at the time of Screening) of corticosteroids or any cytotoxic, immunosuppressive or cytokine-modulating, or receptor- antagonist agent prescribed for rheumatoid arthritis, including but not limited to azathioprine, cyclophosphamide, cyclosporine, etanercept, iloprost, infliximab, leukotriene antagonists, methotrexate, mycophenolate mofetil, tacrolimus, montelukast, tetrathiomolybdate, TNF-α inhibitors, rituximab, abatacept, tofacitintib, tociluzimab.
    8. Able to understand and sign a written informed consent form
    9. For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use two adequate methods of contraception, including at least one method with a failure rate of <1% per year, during the 52 weeks of treatment.
    a. A woman is considered to be of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (≥ 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus).
    b. Examples of contraceptive methods with a failure rate of <1% per year include bilateral tubal ligation, male sterilization, established and proper use of hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices.
    c. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception.
    10. For men who are not surgically sterile: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm, as defined below:
    a. With female partners of childbearing potential, men must remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of < 1% per year during the treatment period and for at least 118 days after the last dose of pirfenidone.
    b. Men must refrain from donating sperm during this same period.
    E.4Principal exclusion criteria
    1.Not a suitable candidate for enrollment or unlikely to comply with the requirements of this study, in the opinion of the investigator
    2. Cigarette smoking or vaping within 3 months of Screening or unwilling to avoid tobacco products throughout the study (this excludes vaping. Vaping is not an exclusion to the study).
    3. History of clinically significant environmental exposure known to cause pulmonary fibrosis (PF), including but not limited to drugs (such as amiodarone), asbestos, beryllium, radiation, and domestic birds
    4. Concurrent presence of other interstitial lung disease, including but not limited to radiation, drug toxicity, sarcoidosis, hypersensitivity pneumonitis, bronchiolitis obliterans organizing pneumonia, human immunodeficiency virus (HIV), viral hepatitis (positive Hep A antibody in the absence of elevated liver enzymes is not an exclusion), and cancer
    5. Concurrent presence of other pleuropulmonary manifestations of RA, including but not limited to rheumatoid nodular disease of the lung, pleuritis/pleural thickening, and obliterative bronchiolitis
    6. Post-bronchodilator FEV1/FVC < 0.7 at Screening
    7. Presence of pleural effusion occupying more than 20% of the hemithorax on Screening HRCT
    8. Clinical diagnosis of a second connective tissue disease or overlap syndrome (including but not limited to scleroderma, Sjogren’s, polymyositis/dermatomyositis, systemic lupus erythematosus)
    9. Coexistent clinically significant COPD/emphysema or asthma in the opinion of the site principle investigator
    10. Clinical evidence of active infection, including but not limited to bronchitis, pneumonia, sinusitis, urinary tract infection, or cellulitis
    11. Any history of malignancy diagnosed within 5 years of screening, other than basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or low grade cervical carcinoma in situ.
    12. History of severe hepatic impairment or end-stage liver disease
    13. History of end-stage renal disease requiring dialysis
    14. History of unstable or deteriorating cardiac or disease, or unstable cardiac arrhythmia or arrhythmia requiring modification of drug therapy, myocardial infarction within the previous year, heart failure requiring hospitalisation
    15. Any condition that, in the opinion of the investigator, might be significantly exacerbated by the known side effects associated with the administration of pirfenidone
    16. Investigational therapy, defined as any drug that has not been approved for marketing for any indication in the country of the participating site, at the time of Screening
    17. History of alcohol or substance abuse in the past 2 years, at the time of Screening
    18. Family or personal history of long QT syndrome
    19. Any of the following liver function test criteria above specified limits:
    a. Total bilirubin above the upper limit of normal (ULN), excluding patients with Gilbert’s syndrome; aspartate or alanine aminotransferase (AST/SGOT or ALT/SGPT) >3 × ULN; alkaline phosphatase >2.5 × ULN
    b. Creatinine clearance (CrCl <30) mL/min, calculated using the Cockcroft-Gault formula
    c. Electrocardiogram (ECG) with a QTcB interval >500 msec at Screening
    20. Prior use of pirfenidone or known hypersensitivity to any of the components of study treatment
    21. Use of any of the following therapies within 28 days before Screening:
    a. Investigational therapy, defined as any drug that has not been approved for marketing for any indication in the country of the participating site
    b. Fluboxamine
    c. Sildenafil (daily use). Note: intermittent use for erectile dysfunction is allowed
    d. Potent CYP1A2 inducers
    21. Any use of an approved anti-fibrotic medication within 28 days of screening.
    E.5 End points
    E.5.1Primary end point(s)
    Incidence of the composite endpoint of decline from baseline in percent predicted FVC of 10% or greater or death during the 52-week treatment period.
    E.5.1.1Timepoint(s) of evaluation of this end point
    52 weeks
    E.5.2Secondary end point(s)
    1. Incidence of the composite endpoint of decline from baseline in percent predicted FVC of 10% or greater during the 52-week treatment period
    2. Frequency of progressive disease as defined by OMERACT: Relative decline from baseline in percent predicted FVC of ≥10%, or relative change from baseline in percent predicted FVC ≥ 5% and < 10%, and ≥15% relative DLCO (Khanna, Mittoo et al. 2015)
    3. Change from baseline to week 52 in absolute value of FVC
    4. Change from baseline to week 52 of percent predicted FVC
    5. Slope of percent predicted FVC over 52-week treatment period
    6. Slope of absolute FVC over 52-week treatment period
    7. Time to decline of 10% or greater in percent predicted FVC at death or over 52-week treatment period
    8. Proportion of participants with all-cause mortality
    9. Proportion of participants with all-cause hospitalization
    10. Proportion of participants with hospitalization for respiratory cause
    11. Number of respiratory exacerbations requiring hospitalizations
    12. Proportion of participants with and number of treatment-emergent AEs
    13. Proportion of participants with and number of treatment-emergent serious adverse events (SAEs)
    14. Proportion of participants with and number of treatment-emergent/treatment-related AEs
    15. Proportion of participants with and number of treatment-emergent/treatment-related SAEs
    16. Proportion of participants with and number of AEs leading to early discontinuation of study treatment
    17. Proportion of participants with and number of treatment-emergent death or transplant
    18. Proportion of participants with and number of treatment-emergent RA-ILD-related mortality
    19. Change from Baseline to Week 52 in dyspnea, as measured by the Dyspnea 12 questionnaire

    Exploratory:
    1. Change from Baseline to Week 52 in Disease Activity Score (DAS) and RAPID3 score (RA disease activity score)
    2. Change from Baseline to Week 52 in Routine Assessment of Patient Index Data 3 (RAPID3) score (RA disease activity score)
    3. Change from Baseline to Week 52 in Erythrocyte Sedimentation Rate (ESR)
    4. Change from Baseline to Week 52 in C-Reactive Protein (CRP)
    5. Candidate biomarker expression in the peripheral blood of patients with RA-ILD over the 52 weeks of treatment and the study follow-up period
    6. Changes from Baseline to 52 weeks in HRCT parameters evaluated by quantitative functional imaging
    7. Changes from Baseline to Week 13, 26, 39 and 52 in the St. George’s Respiratory Questionnaire (SGRQ)
    8. Changes from Baseline to Week 13, 26 and 39 in Dyspnea 12 questionnaire
    9. Changes from Baseline to Week 13, 26, 39 and 52 in Leicester Cough Questionnaire (LCQ)
    10. Changes from Baseline to Week 13, 26, 39 and 52 in the Patient global assessment
    11. Changes from Baseline to Week 13, 26, 39 and 52 in the Health assessment questionnaire
    E.5.2.1Timepoint(s) of evaluation of this end point
    52 weeks
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others Yes
    E.6.13.1Other scope of the trial description
    Biomarkers (role of blood biomarkers in predicting disease progression and survival)
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    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.8.4.1Number of sites anticipated in Member State concerned20
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA4
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Australia
    Canada
    United Kingdom
    United States
    E.8.7Trial has a data monitoring committee Yes
    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
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years4
    E.8.9.1In the Member State concerned months0
    E.8.9.1In the Member State concerned days11
    E.8.9.2In all countries concerned by the trial years4
    E.8.9.2In all countries concerned by the trial months0
    E.8.9.2In all countries concerned by the trial days11
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1Number of subjects for this age range: 0
    F.1.1.1In Utero No
    F.1.1.1.1Number of subjects for this age range: 0
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.2.1Number of subjects for this age range: 0
    F.1.1.3Newborns (0-27 days) No
    F.1.1.3.1Number of subjects for this age range: 0
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.4.1Number of subjects for this age range: 0
    F.1.1.5Children (2-11years) No
    F.1.1.5.1Number of subjects for this age range: 0
    F.1.1.6Adolescents (12-17 years) No
    F.1.1.6.1Number of subjects for this age range: 0
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 60
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 40
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations No
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception No
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state120
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 100
    F.4.2.2In the whole clinical trial 270
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    Treatment of the study treatment (pirfenidone) or placebo will end once their participation in the study has completed. Participants will go back to their normal clinical care after the end of the study.
    G. Investigator Networks to be involved in the Trial
    G.4 Investigator Network to be involved in the Trial: 1
    G.4.1Name of Organisation SABER Statistical Analysis of Biomedical and Educational Research Unit
    G.4.3.4Network Country United States
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2017-10-25
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2017-09-15
    P. End of Trial
    P.End of Trial StatusGB - no longer in EU/EEA
    For support, visit the EMA Service Desk , log in using your EMA account and open a ticket specifying "EU CTR" in your request.
    If you do not have an account, please visit the EMA Account management page page click on "Create an EMA account" and follow the instructions.
    The status of studies in GB is no longer updated from 1.1.2021
    For the UK, as from 1.1.2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2022 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA