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    The EU Clinical Trials Register currently displays   38596   clinical trials with a EudraCT protocol, of which   6341   are clinical trials conducted with subjects less than 18 years old.
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    Summary
    EudraCT Number:2016-002569-68
    Sponsor's Protocol Code Number:APRIL
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:Prematurely Ended
    Date on which this record was first entered in the EudraCT database:2018-05-18
    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 number2016-002569-68
    A.3Full title of the trial
    Safety of abatacept in Rheumatoid Arthritis associated Interstitial Lung Disease: A feasibility study
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Safety of abatacept in Rheumatoid Arthritis associated Interstitial Lung Disease
    A.3.2Name or abbreviated title of the trial where available
    APRIL
    A.4.1Sponsor's protocol code numberAPRIL
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT03084419
    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 SponsorCambridge University Hospitals NHS Foundation 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 supportBristol-Myers Squibb
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationCambridge Clinical Trials Unit
    B.5.2Functional name of contact pointCarrie Bayliss
    B.5.3 Address:
    B.5.3.1Street AddressCambridge University Hospitals NHS Foundation Trust, Addenbrookes Hospital, Coton House, Level 6
    B.5.3.2Town/ cityHills Road, Cambridge
    B.5.3.3Post codeCB2 0QQ
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number01223348158
    B.5.5Fax number01223256763
    B.5.6E-mailcctu@addenbrookes.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 Orencia
    D.2.1.1.2Name of the Marketing Authorisation holderBristol-Myers Squibb Pharmaceuticals Ltd.
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    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 nameOrencia
    D.3.4Pharmaceutical form Powder for concentrate for solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNABATACEPT
    D.3.9.1CAS number 3 332348-12
    D.3.9.4EV Substance CodeAS1
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeup to
    D.3.10.3Concentration number10
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    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 Yes
    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
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Rheumatoid-associated Interstitial Lung Disease (RA-ILD)
    E.1.1.1Medical condition in easily understood language
    We are studying a lung condition called Interstitial Lung Disease that can occur in patients with rheumatoid arthritis. It is characterized by inflammation and scarring of lung tissue.
    E.1.1.2Therapeutic area Diseases [C] - Immune System Diseases [C20]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level PT
    E.1.2Classification code 10022611
    E.1.2Term Interstitial lung disease
    E.1.2System Organ Class 10038738 - Respiratory, thoracic and mediastinal disorders
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10003268
    E.1.2Term Arthritis rheumatoid
    E.1.2System Organ Class 100000004859
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To investigate the safety of abatacept in Rheumatoid arthritis (RA) patients with co-morbid interstitial lung disease (ILD) by estimating the change over time in Forced Vital Capacity (FVC) associated with abatacept therapy in RA-ILD.
    E.2.2Secondary objectives of the trial
    The secondary objectives of this trial study are to assess changes in the following outcome measures (within the first 20 weeks of treatment);
    1. Diffusing capacity of the lung for carbon monoxide (DLCO).
    2. Patient-reported disability associated with dyspnoea (using the MRC dyspnoea grade)
    3. Patient-reported health status related to ILD (using the King’s Brief Interstitial Lung Disease (K-BILD) Questionnaire)
    4. The Disease Activity Score (28 joints) (DAS28) score
    5. The radiological appearances of the ILD, based on semi-quantitative scoring of CT Chest appearances
    6. Average resting oxygen saturation levels
    7. Cough score (using the Leicester Cough Questionnaire)
    8. Overall health status, taking into account the EQ-5D
    9. Number of Respiratory tract infections

    Exploratory objectives
    The exploratory objectives of this trial are to assess the changes in the following outcome measures (within the first 20 weeks of treatment);
    1. Possible biomarkers of RA-ILD assessed using BAL fluid an
    E.2.3Trial contains a sub-study No
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    1. Mechanisms of action study.
    Hypothesis: “As a consequence of reduced T-lymphocyte signalling in the lung, abatacept will modulate the lung immune response”

    Objectives:
    a) To identify the cell subsets contributing to the aetio-pathogenesis of RA-ILD by performing immunophenotyping in both peripheral blood and BAL.
    b) To determine the effect of abatacept on T cell immunophenotype profile.


    2. Microbiome.

    Objective:
    To perform a qualitative assessment of the effect of abatacept on the lung microbiome.
    E.3Principal inclusion criteria
    • Aged 18 years or over (for patients aged 65 and over, additional caution should be taken to assess their health status prior to inclusion)
    • Agree to use 2 acceptable forms of effective contraception for the duration of the study trial and a further 14 weeks after completion
    • Meet a diagnosis of RA by 2010 EULAR/ACR criteria
    • Have interstitial lung disease associated with RA, with supportive findings on their PFTs and CT Chest scans. Participants will be included if their ILD has not responded to conventional immunosuppressive therapy, or has progressed over 24 weeks, regardless of the severity of the ILD at the time of inclusion to the trial. Progression will be defined as EITHER a decrease in either FVC or DLCOc by at least 5% over 6 months or 10% over 12 months (or by (0.83 x m)%, where m =number of months’ interval between a pair of lung function tests done within the last 18 months) OR progression of lung fibrosis on a high-resolution CT chest, as reported by a chest radiologist.
    E.4Principal exclusion criteria
    The presence of any of the following will preclude patient participant inclusion:
    • Unable to provide written informed consent
    • Participants who are taking other immunosuppressants, e.g. mycophenolate mofetil (MMF), unless this has been discontinued with an adequate washout period. The exceptions to this exclusion criterion are methotrexate (MTX) and hydroxychloroquine, which are allowed provided the dose has been stable for 6 weeks prior to baseline (visit 2).
    • Participants who have been taking > 10mg Prednisolone daily within the last 6 weeks prior to baseline (visit 2)
    • Participants who have had rituximab, within the 24 weeks prior to baseline (Visit 2)
    • Any participant with active signs or symptoms of infection at the time of recruitment baseline (visit 2) or requiring antibiotic treatment within the preceding 4 weeks
    • Any participant with significant co-existing lung disease, such as asthma, bronchiectasis, emphysema, Chronic Obstructive Pulmonary Disease (COPD) or if their pre-bronchodilator FEV1/FVC ratio is < 70%.
    • Significant other co-morbidity (e.g. active malignancy/liver disease/renal disease) within the last 5 years
    • Prior use of abatacept at any time
    • Participation in any other clinical trial within 8 weeks or 5 half-lives of IMP, whichever is longer, prior to baseline (visit 2) (participation in ‘observational’ studies is allowed)
    • Hypersensitivity to any excipients of abatacept
    • Any participant who has had live vaccines within 6 weeks prior to baseline (Visit 2)
    • Participant is pregnant or breastfeeding
    E.5 End points
    E.5.1Primary end point(s)
    The primary outcome for this study is the change in forced vital capacity (FVC) after 20 weeks of treatment with abatacept.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Evaluation at week 24 (following 20 weeks of treatment with abatacept)
    E.5.2Secondary end point(s)
    Secondary end points include:
    • Diffusing capacity of the lung for carbon monoxide (DLCO)
    • MRC dyspnoea score
    • Kings Brief Interstitial Lung Disease score (K-BILD)
    • Semi-quantitative radiological scoring of the ILD based on CT Chest appearances before and after abatacept
    • Resting oxygen saturation
    • DAS28
    • Leicester Ccough Questionnaire score
    • EQ-5D (a standardised measure of health status by the EuroQol group)
    • Respiratory tract infection

    Exploratory end points
    • Biomarker analysis

    E.5.2.1Timepoint(s) of evaluation of this end point
    Evaluation at week 24 (following 20 weeks of treatment with abatacept)
    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 Yes
    E.6.4Safety Yes
    E.6.5Efficacy No
    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 No
    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 No
    E.8.1.1Randomised No
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    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 No
    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 concerned2
    E.8.5The trial involves multiple Member States No
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA No
    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 years2
    E.8.9.1In the Member State concerned months0
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months0
    E.8.9.2In all countries concerned by the trial days0
    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: 25
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 5
    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 state30
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 30
    F.4.2.2In the whole clinical trial 30
    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)
    Abatacept (Orencia) is licensed for use in the UK.

    It’s use is also approved in the NICE technology appraisal guidance [TA375]
    G. Investigator Networks to be involved in the Trial
    G.4 Investigator Network to be involved in the Trial: 1
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2018-03-09
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2018-05-04
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
    P.Date of the global end of the trial2020-09-09
    As of 1.2.2020, the UK is no longer an EU Member State. However, EU law still applies to the UK during the transition period
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
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