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    Summary
    EudraCT Number:2011-003678-97
    Sponsor's Protocol Code Number:AGO/2011/005
    National Competent Authority:Belgium - FPS Health-DGM
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2011-09-07
    Trial results View 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 ConcernedBelgium - FPS Health-DGM
    A.2EudraCT number2011-003678-97
    A.3Full title of the trial
    Exploration of TNF-alpha Blockade with golimumab in the Induction of Clinical Remission in Patients with Early peripheral SpondyloArthritis (SpA) according to ASAS-criteria (‘CRESPA’).
    Exploratie van TNF alfa blokkade met golimumab met als doel het induceren van klinische remissie bij patiënten met perifere spondyloarthropathie met vroegtijdige aantasting die voldoen aan de huidige ASAS criteria (CRESPA).
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Exploration of TNF-alpha Blockade with golimumab in the Induction of Clinical Remission in Patients with Early Peripheral Spondyloarthritis (SpA) according to ASAS-criteria
    Exploratie van TNF alfa blokkade met golimumab met als doel het induceren van klinische remissie bij patiënten met perifere spondyloarthropathie met vroegtijdige aantasting die voldoen aan de huidige ASAS criteria (CRESPA).
    A.4.1Sponsor's protocol code numberAGO/2011/005
    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 SponsorGhent University Hospital
    B.1.3.4CountryBelgium
    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 supportGheny University Hospital
    B.4.2CountryBelgium
    B.4.1Name of organisation providing supportJanssen Biologics BV
    B.4.2CountryNetherlands
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationGhent University Hospital
    B.5.2Functional name of contact pointBimetra Clinics
    B.5.3 Address:
    B.5.3.1Street AddressDe Pintelaan 185
    B.5.3.2Town/ cityGhent
    B.5.3.3Post code9000
    B.5.3.4CountryBelgium
    B.5.4Telephone number3293320500
    B.5.5Fax number3293320520
    B.5.6E-mailBimetra.Clinics@uzgent.be
    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 Simponi
    D.2.1.1.2Name of the Marketing Authorisation holderJanssen Biologics B.V.
    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 namegolimumab
    D.3.4Pharmaceutical form Solution for injection in pre-filled syringe
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSubcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNGOLIMUMAB
    D.3.9.1CAS number 476181-74-5
    D.3.9.4EV Substance CodeSUB25638
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number50
    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.IMP: 2
    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 LEDERTREXATE
    D.2.1.1.2Name of the Marketing Authorisation holderPfizer NV
    D.2.1.2Country which granted the Marketing AuthorisationBelgium
    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 nameLEDERTREXATE
    D.3.4Pharmaceutical form Tablet
    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 INNMETHOTREXATE DISODIUM
    D.3.9.3Other descriptive nameMETHOTREXATE DISODIUM
    D.3.9.4EV Substance CodeSUB16442MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number2.74
    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 placeboSolution for injection in pre-filled syringe
    D.8.4Route of administration of the placeboSubcutaneous use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Early stage peripheral Spondyloarthritis (SpA)
    Vroegtijdige Perifere sponyloarthropathie
    E.1.1.1Medical condition in easily understood language
    Early stage Peripheral Spondyloarthritis
    Perifere spondyloarthropathie met vroegtijdige aantasting
    E.1.1.2Therapeutic area Diseases [C] - Musculoskeletal Diseases [C05]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 18.1
    E.1.2Level LLT
    E.1.2Classification code 10056449
    E.1.2Term Spondyloarthrosis
    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 explore the potential of an induction therapy with the TNF-blocking agent golimumab (Simponi® in a very early disease stage (less than 3 months of symptom duration) of patients with predominant peripheral Spondyloarthritis (SpA), classified according to the new ASAS-criteria.

    In the open-label ‘CRESPA-extension’ part of the study, we want to investigate the long-term safety and efficacy of golimumab administered every 4 weeks at a dose of 50 mg subcutaneously (SC) for a total period of 116 weeks (104 weeks golimumab monotherapy + 12 weeks combination therapy with methotrexate 10-15 mg weekly).
    E.2.2Secondary objectives of the trial
    Exploration for:
    - The improvement in the tender and swollen joint count.
    - The improvement in dactylitis with obtaining a circumference measurement and clinical picture.
    - The improvement in enthesitis, using the different scoring systems with inclusion of all relevant entheses.
    - The improvement in global measurements of disease activity: patient global assessment of disease activity, patient pain assessment (peripheral and axial pain), physician global assessment of disease activity, ...)
    - Of the utility of conventional ankylosing spondylitis measurements such as BASDAI, BASFI, BASMI
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    - Subject is ≥ 18 years of age
    - Subjects must meet the new ASAS classification criteria for peripheral spondyloarthritis
    - Subjects must have had onset of peripheral SpA symptoms ≤ 3 months prior to the screening visit
    - Subjects must have active disease at screening and baseline, defined by Patient Global Assessment of Disease Activity VAS ≥ 40mm and Patient Global Assessment of Pain VAS ≥ 40mm at screening and baseline visits.
    - In subjects with concurrent axial SpA symptoms, the peripheral SpA symptoms must be the predominant symptoms at study entry based on the Investigator’s clinical judgment.
    - Subject has a negative PPD test (or equivalent) and Chest radiography (PA and lateral view) at screening. If the subject has a positive PPD test (or equivalent), has had a past ulcerative reaction following PPD placement and/or a Chest radiography consistent with prior TB exposure, the subject must initiate, or have documented completions of a course of anti-TB therapy.
    - Patients must undergo screening for HBV (this includes testing for HBsAg (surface antigen), anti-HBs (surface antibody) and anti-HBc total (core antibody total).
    - Women of childbearing potential or men capable of fathering children must be using adequate birth control measures during the study and for 6 months after receiving the last administration of study agent. Female patients of childbearing potential must test negative for pregnancy.
    - If female, subject is either not of childbearing potential, defined as postmenopausal for at least 1 year or surgically sterile (bilateral tubal ligation, bilateral oophorectomy or hysterectomy) or is of childbearing potential and is practicing an approved method of birth control throughout the study and for 6 months after last dose of study drug.
    - Female subjects must agree to not donate eggs (ova, oocytes) during the study and for 6 months after last dose of study agent. Male subjects must agree to not donate sperm while in the study and for 6 months after last dose of study agent
    - Subject is judged to be in good health as determined by the principal investigator based upon the results of medical history, laboratory profile, physical examination, chest x-ray (CXR), and a 12-lead electrocardiogram (ECG) performed during screening.
    - Subjects must be able and willing to provide written informed consent and comply with the requirements of this study protocol.
    - Subjects must be able and willing to self-administer sc injections or have a qualified person available to administer sc injections.

    CRESPA-Extension’
    Subjects will be allowed to participate in the ‘CRESPA-Extension’ part of the study if they are considered good candidates for chronic anti-TNF treatment and fulfill one of the following 2 scenarios:
    - Patients participating in ‘CRESPA’ that experienced “sustained clinical remission of arthritis/enthesitis/dactylitis on 2 consecutive major study visits, and in whom withdrawal of golimumab treatment provoked a flare of peripheral SpA during the follow-up.
    - Patients participating in ‘CRESPA’ that experienced a major improvement at the week 48 ‘end-of-study’ visit, without however reaching clinical remission. Major improvement is defined as “Peripheral SpA Response Criteria at 40%” (PSpARC 40):
    - ≥40% improvement (minimum 20 mm absolute improvement) from baseline in Patient Global Assessment of Disease Activity on a 100 mm Visual Analogue Scale (VAS) and
    - ≥40% improvement (minimum 20 mm absolute improvement) from baseline in Patient Global Assessment of Pain on a 100 mm Visual Analogue Scale (VAS) and
    - ≥40% improvement from baseline in at least 1 of the following 3 criteria:
    - Swollen 76-Joint Count (SJC) and Tender 78-Joint Count (TJC)
    - Enthesitis Count
    - Dactylitis Count
    E.4Principal exclusion criteria
    - Medical history of inflammatory arthritis of a different etiology other than peripheral spondyloarthritis (e.g. rheumatoid arthritis, systemic lupus erythematosus, gout, or any arthritis with onset prior to age 16 years such as JIA).
    - Prior exposure to any biologic therapy with a potential therapeutic impact on SpA, including anti-TNF therapy.
    - Treatment with any investigational drug of chemical or biological nature within a minimum of 30 days or 5 half lives (whichever is longer) of the drug prior to the Baseline Visit.
    - Infection(s) requiring treatment with intravenous (iv) anti-infectives within 30 days prior to the Baseline visit or oral anti-infectives within 14 days prior to the Baseline Visit.
    - Have a known hypersensitivity to human immunoglobulin proteins or other components of golimumab.
    - History of CNS demyelinating disease or neurologic symptoms suggestive of CNS demyelinating disease.
    - History of listeriosis, histoplasmosis, chronic of active Hepatitis B infection, Hepatitis C infection, human immunodeficiency virus (HIV) infection, immunodeficiency syndrome, chronic recurring infections or active TB.
    - Have a history of, or concurrent, CHF, including medically controlled, asymptomatic CHF.
    - Evidence of dysplasia or history of malignancy (including lymphoma and leukemia) other than a successfully treated non-metastatic cutaneous squamous cell or basal cell carcinoma or localized carcinoma in situ of the cervix.
    - Have received, or are expected to receive, any live virus or bacterial vaccination within 3 months prior to the first administration of study agent, during the trial, or within 6 months after the last administration of study agent.
    - Positive pregnancy test at screening or baseline.
    - Female subjects who are breast-feeding or considering becoming pregnant during the study.
    - History of clinically significant drug or alcohol abuse in the last 12 months.
    - Clinically significant abnormal screening laboratory results as evaluated by the Investigator.
    - Positive rheumatoid factor (RF) or anti-cyclic citrullinated peptide (anti-CCP) antibody at screening if the titers are crossing 3 times the upper limit of the normal
    - Subject is considered by the investigator, for any reason, to be an unsuitable candidate for the study.
    - Subject with diagnosis and current symptoms of fibromyalgia.
    E.5 End points
    E.5.1Primary end point(s)
    the induction of clinical remission (complete resolution of synovitis/dactylitis/enthesitis which was present at baseline) and prevention of newly developing peripheral and/or axial spondylarthritis signs).
    The primary analysis will be a comparison at 24 weeks of the percentage of patients with a PSpARC 40 response in the group treated with the TNF-blocking agent versus placebo (for patients who were treated via the open-label Golimumab escape arm, an approach based upon last observation carried forward (LOCF) and non-responder imputation (NRI) will be used).
    E.5.1.1Timepoint(s) of evaluation of this end point
    At 24 weeks.
    E.5.2Secondary end point(s)
    I. In this study we will also evaluate the safety of TNF-α blockade in patients with early peripheral spondyloarthritis.
    II. Comparison between the group treated with the anti-TNF blocking agent versus placebo at week 12 (and if applicable at week 24) for:
     The percentage of patients achieving Peripheral Spondyloarthritis Response Criteria at different levels of response (e.g. PSpARC 40).
     The percentage of patients for whom early escape was necessary.
     The improvement in the tender and swollen joint count.
     The improvement in dactylitis count and semiquantitative score of severity (mild, moderate, severe).with obtaining a circumference measurement and clinical picture.
     The improvement in enthesitis count, using the different scoring systems with inclusion of all relevant entheses.
     The improvement in global measurements of disease activity: patient global assessment of disease activity, patient pain assessment (peripheral and axial pain), physician global assessment of disease activity, ...).
     The exploration of the utility of conventional ankylosing spondylitis measurements such as BASDAI, BASFI, BASMI.

    III. Longitudinal comparison versus baseline of efficacy parameters described below over the first 24 weeks. Potentially 3 groups will be compared: the group treated with placebo until week 24, the group treated with placebo until week 12 followed by the anti-TNF blocking agent, and the group treated with the anti-TNF blocking agent from baseline.
     The percentage of patient in clinical remission (absence of arthritis, enthesitis and dactylitis).
     The improvement in the tender and swollen joint count.
     The improvement in dactylitis count and semiquantitative score of severity (mild, moderate, severe).
     The improvement in enthesitis count, using the different scoring systems with inclusion of all relevant entheses.
     The improvement in global measurements of disease activity: patient global assessment of disease activity, patient pain assessment (peripheral and axial pain), physician global assessment of disease activity, ...).
     The exploration of the utility of conventional ankylosing spondylitis measurements such as BASDAI, BASFI, BASMI.
    E.5.2.1Timepoint(s) of evaluation of this end point
    - at 3 months (week 12) in comparison with baseline
    - at 6 months (week 24) in comparison with baseline
    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 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 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) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    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 Yes
    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.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    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 No
    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
    Last visit last subject
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years3
    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 years0
    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.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 40
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 20
    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 Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    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 state60
    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)
    Possible follow up in a prospective patient register for inflammatory arthritis in the Ghent University Hospital, or or participation in the CRESPA extension study.
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2011-09-14
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2011-11-09
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2019-04-30
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