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    Summary
    EudraCT Number:2021-000679-35
    Sponsor's Protocol Code Number:APHP2000231
    National Competent Authority:France - ANSM
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2021-06-25
    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 ConcernedFrance - ANSM
    A.2EudraCT number2021-000679-35
    A.3Full title of the trial
    SATELITE “Salvage Therapy for Patients with Inadequate Response to Standard of Care Therapy in Granulomatosis with Polyangiitis”
    SATELITE "Traitement de sauvetage pour les patients ayant une réponse inadéquate au traitement de référence dans la granulomatose avec polyangéite"
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    SATELITE “Salvage Therapy for Patients with Inadequate Response to Standard of Care Therapy in Granulomatosis with Polyangiitis”
    SATELITE "Traitement de sauvetage pour les patients ayant une réponse inadéquate au traitement de référence dans la granulomatose avec polyangéite"
    A.3.2Name or abbreviated title of the trial where available
    SATELITE
    SATELITE
    A.4.1Sponsor's protocol code numberAPHP2000231
    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 SponsorASSISTANCE PUBLIQUE - HOPITAUX DE PARIS (AP-HP)
    B.1.3.4CountryFrance
    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 supportASSISTANCE PUBLIQUE - HOPITAUX DE PARIS
    B.4.2CountryFrance
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationASSISTANCE PUBLIQUE - HOPITAUX DE PARIS
    B.5.2Functional name of contact pointDRCI Hôpital St Louis
    B.5.3 Address:
    B.5.3.1Street Address1 av. Claude Vellefaux
    B.5.3.2Town/ cityPARIS
    B.5.3.3Post code75010
    B.5.3.4CountryFrance
    B.5.4Telephone number0144841722
    B.5.5Fax number0144841701
    B.5.6E-mailkarine.goude@aphp.fr
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleComparator
    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 Rituximab
    D.2.1.1.2Name of the Marketing Authorisation holderRoche Registration GmbH
    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.3.4Pharmaceutical form 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 INNRITUXIMAB
    D.3.9.1CAS number 174722-31-7
    D.3.9.4EV Substance CodeSUB12570MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    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) Yes
    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 ROACTEMRA
    D.2.1.1.2Name of the Marketing Authorisation holderRoche Registration Limited
    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.3.4Pharmaceutical form Solution for injection
    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 INNTOCILIZUMAB
    D.3.9.1CAS number 375823-41-9
    D.3.9.4EV Substance CodeSUB20313
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number180
    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) Yes
    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: 3
    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 Pharma EEIG
    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.3.4Pharmaceutical form Solution for injection
    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 INNABATACEPT
    D.3.9.1CAS number 332348-12-6
    D.3.9.4EV Substance CodeSUB20635
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number125
    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: 4
    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 Methotrexate
    D.2.1.1.2Name of the Marketing Authorisation holderNordic Group 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.3.4Pharmaceutical form Solution for injection
    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.3.9.3Other descriptive nameMETHOTREXATE
    D.3.9.4EV Substance CodeSUB08856MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number25
    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) Yes
    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.IMP: 5
    D.1.2 and D.1.3IMP RoleComparator
    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 Mycophénolate mofétil
    D.2.1.1.2Name of the Marketing Authorisation holderRoche Registration GmbH
    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.3.4Pharmaceutical 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.3.9.3Other descriptive nameMYCOPHENOLATE MOFETIL
    D.3.9.4EV Substance CodeSUB03360MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typerange
    D.3.10.3Concentration number250 to 500
    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.IMP: 6
    D.1.2 and D.1.3IMP RoleComparator
    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 Azathioprine
    D.2.1.1.2Name of the Marketing Authorisation holderASPEN PHARMA TRADING LIMITED
    D.2.1.2Country which granted the Marketing AuthorisationFrance
    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.3.4Pharmaceutical 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.3.9.1CAS number 446-86-6
    D.3.9.3Other descriptive nameAZATHIOPRINE
    D.3.9.4EV Substance CodeSUB05647MIG
    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 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
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Granulomatosis with Polyangiitis
    Granulomatose avec polyangéite
    E.1.1.1Medical condition in easily understood language
    Granulomatosis with Polyangiitis
    Granulomatose avec polyangéite
    E.1.1.2Therapeutic area Diseases [C] - Blood and lymphatic diseases [C15]
    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
    The primary objective of this study is to identify the most promising therapeutic strategy for patients with inadequate response to standard of care therapy in granulomatosis with polyangiitis. It will evaluate the efficacy to induce remission of three different salvage strategies including: a combination of rituximab with addition of a conventional disease-modifying antirheumatic drugs (cDMARD) (either methotrexate, azathioprine or mycophenolate mofetil, but preferentially methotrexate); tocilizumab; or abatacept.
    L’objectif principal de cette étude est d'identifier la stratégie thérapeutique la plus prometteuse pour les patients qui ont une GPA avec une réponse inadéquate au traitement de référence. Elle évaluera l'efficacité pour l’induction de la rémission de trois stratégies thérapeutiques de sauvetage différentes : une combinaison de rituximab en association avec un cDMARD (soit le méthotrexate, soit l'azathioprine, soit le mycophénolate mofétil, avec de préférence le méthotrexate) ; un relai par du tocilizumab ; ou un relai par de l'abatacept.
    E.2.2Secondary objectives of the trial
    To evaluate the safety profile (adverse events), the corticosteroids dose, the sequelae, the functional disability and quality of life, the patient-reported outcomes (PRO) and the evolution of ANCA titers in each salvage therapy group.
    Évaluer le profil de sécurité (événements indésirables), la dose de corticostéroïdes, les séquelles, le handicap fonctionnel et la qualité de vie, les patient reported outcomes (PRO) ou « résultats rapportés par les patients » et l'évolution des titres ANCA dans chaque groupe.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    (1) Newly diagnosed or relapsing granulomatosis with polyangiitis according to American College of Rheumatology criteria, EMA classification algorithm and/or the 2012 revised Chapel Hill Consensus Conference definition
    (2) Aged 18 years or older
    (3) Active clinical manifestations attributable to GPA
    (4) An inadequate response to previous standard of care therapy including:
    a. Both a combination of glucocorticoids plus cyclophosphamide and a combination of glucocorticoids plus rituximab
    b. Or an inadequate response to a combination of glucocorticoids plus rituximab and a contraindication to cyclophosphamide
    (5) An inadequate response to treatment defined as follows:
    a. A progressive disease unresponsive to previous standard of care therapy after 12 weeks of treatment
    b. Or a lack of response, defined as 50% reduction in the disease activity, after 12 weeks of treatment
    c. Or a persistent active disease attributable to either a vasculitic or a granulomatous manifestation of GPA that requires the maintenance of corticosteroids 7.5 mg/day of equivalent prednisone after 12 weeks of treatment
    (6) A stable dose of oral glucocorticoids of ≥ 7.5 mg/day of equivalent prednisone within the 4 weeks before enrollment. Pulses of methylprednisolone (1 to 3 pulses of 7.5 to 15 mg/kg each; ≤ 1000 mg) are allowed if necessary, according to severity before starting the experimental treatment
    (7) A stable dose of conventional disease-modifying anti-rheumatic drugs (cDMARD) within 4 weeks before enrollment if the patient is currently treated with a cDMARD
    (8) Patients must have the ability to understand the requirements of the study, provide written informed consent prior to participation in the study (including consent for the use and disclosure of research-related health information) and comply with the study protocol procedures (including required study visits)
    (9) Patients must have an affiliation with a mode of social security (profit or being entitled)
    (1) GPA nouvellement diagnostiquée ou récidivante selon les critères de l'American College of Rheumatology, l'algorithme de classification de l'EMA et/ou la définition révisée de la conférence de consensus de Chapel Hill de 2012.
    (2) Âgés de 18 ans ou plus.
    (3) Manifestations cliniques actives attribuables à la GPA.
    (4) Une réponse inadéquate à un traitement de référence comprenant :
    a. Une combinaison de glucocorticoïdes plus cyclophosphamide et une combinaison de glucocorticoïdes plus rituximab.
    b. OU une combinaison de glucocorticoïdes et de rituximab et une contre-indication au cyclophosphamide.
    (5) Une réponse inadéquate au traitement définie comme suit :
    a. Une maladie progressive ne répondant pas au traitement de référence après 12 semaines de traitement.
    b. OU l’absence de réponse, définie comme une réduction de 50 % du score d'activité de la maladie, après 12 semaines de traitement.
    c. OU une maladie active persistante attribuable à une manifestation vasculitique ou granulomateuse de la GPA qui nécessite le maintien des corticostéroïdes à une dose ≥ 7,5 mg/jour d’équivalent prednisone après ≥ 12 semaines de traitement.
    (6) Une dose stable de glucocorticoïdes oraux à une posologie ≥ 7,5 mg/jour d’équivalent prednisone dans les 4 semaines précédant l’inclusion. Des bolus de méthylprednisolone (1 à 3 bolus de 7,5 à 15 mg/kg chacun ; ≤ 1000 mg) sont autorisées si nécessaire, selon la gravité, avant de commencer le traitement expérimental.
    (7) Une dose stable de cDMARD dans les 4 semaines précédant l'inscription dans le cas où me patient est en cours de traitement par un cDMARD.
    (8) Les patients doivent être en mesure de comprendre les contraintes de l'étude, de fournir un consentement éclairé écrit avant de participer à l'étude (y compris le consentement à l'utilisation et à la communication de données concernant sa santé liées à la recherche) et de se conformer aux procédures du protocole de l'étude (y compris les visites d'étude requises).
    (9) Les patients doivent être affiliés à un régime de sécurité sociale (à but lucratif ou de droit).
    E.4Principal exclusion criteria
    (1) An allergy or hypersensitivity to monoclonal antibodies or either of the study drugs (rituximab, prednisone, abatacept or tocilizumab) or to their excipients
    (2) A previous treatment with a combination of rituximab plus a cDMARD, with abatacept, or with tocilizumab
    (3) A contraindication to a combination of rituximab plus a cDMARD, to abatacept, or to tocilizumab (including an ongoing infection; history of recent cancer <5 years before enrollment, except for cured non-melanoma skin cancer); pregnancy; and breastfeeding
    (4) Patients with severe vasculitis manifestations that requires plasma exchange therapy including severe renal failure with a creatinine level ≥350 µmol/L or severe alveolar haemorrhage
    (5) Patients with vasculitis in remission
    (6) Patients with symptoms attributable to chronic and non-active GPA
    (7) Patients with severe cardiac failure defined as class IV in New York Heart Association
    (8) Patients with acute infections or chronic active infections (including HIV, HBV or HCV)
    (9) Patients with active cancer or recent cancer (<5 years), except basocellular carcinoma and prostatic cancer of low activity controlled by hormonal treatment
    (10) Pregnant women and lactation. Patients with childbearing potential should have reliable contraception for the 12 months duration of the study
    (11) Patients with other uncontrolled diseases, including drug or alcohol abuse, severe psychiatric diseases that could interfere with participation in the trial according to the protocol
    (12) Patients included in other investigational therapeutic study within the previous 3 months
    (13) Patients suspected not to be observant to the proposed treatments
    (14) Laboratory parameter exclusions:
    a. aspartate or alanine aminotransferase (AST/SGOT or ALT/SGPT) > 5 times upper limit of normal
    b. Platelet count <100.000/mm3
    c. White blood cell count <2000/mm3
    (15) Hepatic Failure
    (1) Une allergie ou une hypersensibilité aux anticorps monoclonaux ou à l'un des médicaments de l'étude (rituximab, prednisone, abatacept ou tocilizumab) ou à leurs excipients.
    (2) Un antécédent de traitement par une combinaison de rituximab plus un cDMARD, par abatacept ou par tocilizumab.
    (3) Une contre-indication à une combinaison de rituximab plus un cDMARD, à l'abatacept ou au tocilizumab (comprenant une infection en cours ; un antécédent de cancer récent < 5 ans avant l’inclusion, sauf pour le cancer de la peau guéri non mélanome) ; la grossesse ; et l’allaitement.
    (4) Patients présentant des manifestations sévères de la vascularite nécessitant un recours aux échanges plasmatiques, dont une insuffisance rénale aiguë sévère avec un taux de créatinine ≥ 350 µmol/L ou une hémorragie alvéolaire sévère.
    (5) Patients atteints de vascularite en rémission.
    (6) Patients présentant des symptômes attribuables à une GPA chronique et non active.
    (7) Patients souffrant d'insuffisance cardiaque sévère définie comme classe IV de la classification de la New York Heart Association.
    (8) Patients souffrant d'infections aiguës ou d'infections chroniques actives (y compris le VIH, le VHB ou le VHC).
    (9) Patients présentant un cancer actif ou un cancer récent (<5 ans), sauf carcinome basocellulaire et cancer prostatique de faible activité contrôlés par un traitement hormonal.
    (10) Femmes enceintes et allaitement. Les patientes en âge de procréer doivent bénéficier d'une contraception fiable pendant les 12 mois de l'étude.
    (11) Patients souffrant d'autres maladies non contrôlées, comprenant l'abus de drogues ou d'alcool, des maladies psychiatriques sévères, qui pourraient interférer avec la participation à l'essai thérapeutique.
    (12) Patients inclus dans un autre essai thérapeutique interventionnel au cours des 3 mois précédents.
    (13) Patients avec une mauvaise observance prévisible.
    (14) Critères biologiques d’exclusion :
    a) une aspartate ou alanine aminotransférase (AS / SGOT ou ALT / SGPT)> 5 fois la limite supérieure de la normale;
    b) Plaquettes <100 000 / mm3;
    c) Globules blancs <2000 / mm3.
    (15) Insuffisance hépatique
    E.5 End points
    E.5.1Primary end point(s)
    The primary endpoint will be the proportion of patients with a response or a remission at 12 weeks as defined according to the EULAR recommendations.
    Remission is defined as the absence of disease activity attributable to active disease qualified by the need for ongoing stable maintenance immunosuppressive therapy. The term ‘‘active disease’’ is not restricted to vasculitis only, but also includes other inflammatory features like granulomatous inflammation. Response is defined as a 50% reduction of disease activity score and absence of new manifestations.
    Evaluation of remission and response will be determined according to the EULAR recommendations by the investigator in charge of the patient and secondarily validated blindly by an Endpoint Adjudication Committee.
    Le critère de jugement principal sera la proportion de patients en réponse ou en rémission à 12 semaines, selon les définitions de l'EULAR.
    La rémission est définie comme l'absence d'activité de la maladie attribuable à une maladie active, caractérisée par la nécessité d'un traitement immunosuppresseur d'entretien à dose stable. Le terme "maladie active" n'est pas limité à la vascularite uniquement, mais inclut également d'autres caractéristiques inflammatoires comme l'inflammation granulomateuse. La réponse est définie comme une réduction de 50 % du score d'activité de la maladie et l'absence de nouvelles manifestations.
    L'évaluation de la rémission et de la réponse sera déterminée selon les recommandations EULAR par l'investigateur en charge du patient et validée secondairement en aveugle par un comité d’adjudication.
    E.5.1.1Timepoint(s) of evaluation of this end point
    12 weeks
    12 semaines
    E.5.2Secondary end point(s)
    - The proportion of patients with a response or a remission according to the EULAR recommendations at week 26 and 52.
    - The difference between the physician’s and patient’s global assessment of disease activity between baseline and week 12 and between baseline and week 52.
    - The patient-reported outcomes (PRO) including: HAQ, SF-36 and VAA-PRO at week 12, 24 and 52.
    - The number of adverse events, expressed as adverse events according to the CTCAE toxicity grading system per patient-year at week 26 and 52 for the following adverse events combined: death (all causes), grade 2 or higher leukopenia or thrombocytopenia, grade 3 or higher infections, hemorraghic cystitis, malignancies, venous thromboembolic events, hospitalization resulting either from the disease or from a complication due to the study treatment, infusion reactions (within 24 hours of infusion) that result in the cessation of further infusions.
    - The area under the curve for corticosteroids at week 26 and 52.
    - The Vasculitis Damage Index at week 26 and 52.
    - Evolution of ANCA titers in the treatment groups.
    - La proportion de patients ayant obtenu une réponse ou une rémission selon les recommandations EULAR à la semaine 26 et 52.
    - La différence entre l'évaluation globale de l'activité de la maladie par le médecin et par le patient entre le point de départ et la semaine 12 et entre le point de départ et la semaine 52.
    - Les PRO, comprenant les questionnaires HAQ, SF-36 et VAA-PRO, à la semaine 12, 24 et 52
    - Le nombre d'événements indésirables, exprimé en tant qu'événements indésirables selon le système de classification de la toxicité du CTCAE par patient et par an, aux semaines 26 et 52 pour les événements indésirables suivants combinés : décès (toutes causes confondues), leucopénie ou thrombocytopénie de grade 2 ou supérieur, infections de grade 3 ou supérieur, cystite hémorragique, cancer, événements thromboemboliques veineux, hospitalisation résultant soit de la maladie soit d'une complication due au traitement de l'étude, réactions à la perfusion (dans les 24 heures suivant la perfusion) qui entraînent l'arrêt des perfusions ultérieures.
    - L'aire sous la courbe pour les corticostéroïdes à la semaine 24 et 52.
    - Le score Vasculitis Damage Index (indice de dommage de la vascularite) à la semaine 26 et 52.
    - L'évolution du titre des ANCA dans les différents groupes de traitement.
    E.5.2.1Timepoint(s) of evaluation of this end point
    52 weeks
    52 semaines
    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 No
    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 Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other Yes
    E.8.1.7.1Other trial design description
    Pick the winner design
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) Yes
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial3
    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 concerned50
    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
    LVSL
    LVSL
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years
    E.8.9.1In the Member State concerned months48
    E.8.9.1In the Member State concerned days
    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: 21
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 21
    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 state42
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 42
    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)
    None
    Aucun
    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 Decision2021-09-07
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2021-07-28
    P. End of Trial
    P.End of Trial StatusOngoing
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