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    Summary
    EudraCT Number:2019-003383-47
    Sponsor's Protocol Code Number:TAK-079-1005
    National Competent Authority:Italy - Italian Medicines Agency
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2020-09-25
    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 ConcernedItaly - Italian Medicines Agency
    A.2EudraCT number2019-003383-47
    A.3Full title of the trial
    A Phase 2, Randomized, Placebo-Controlled Study to Evaluate Safety, Tolerability, and Efficacy of TAK-079 in Patients With Generalized Myasthenia Gravis
    Studio di fase 2, randomizzato, controllato con placebo per valutare la sicurezza, la tollerabilità e l'efficacia di TAK-079 in pazienti affetti da miastenia grave generalizzata
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Study to Investigate the Safety, Tolerability, and Efficacy of TAK-079 in Participants With Generalized Myasthenia Gravis
    Studio per valutare la sicurezza, la tollerabilità e l'efficacia di TAK-079 in partecipanti affetti da miastenia grave generalizzata
    A.3.2Name or abbreviated title of the trial where available
    -
    -
    A.4.1Sponsor's protocol code numberTAK-079-1005
    A.5.3WHO Universal Trial Reference Number (UTRN)U1111-1234-4442
    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 SponsorMILLENNIUM PHARMACEUTICALS, INC.
    B.1.3.4CountryUnited States
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportMillennium Pharmaceuticals, Inc. (Takeda)
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationMillennium Pharmaceuticals, Inc. (Takeda)
    B.5.2Functional name of contact pointDrug Information Call Center
    B.5.3 Address:
    B.5.3.1Street Address40 Landsdowne Street
    B.5.3.2Town/ cityCambridge, MA
    B.5.3.3Post code02139
    B.5.3.4CountryUnited States
    B.5.4Telephone number0015107402412
    B.5.5Fax number0018008816092
    B.5.6E-mailmedical@mlnm.com
    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 No
    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 nameTAK-079
    D.3.2Product code [TAK-079, TSF-021, TSF79]
    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 INNTAK-079
    D.3.9.2Current sponsor codeTAK-079
    D.3.9.3Other descriptive nameTAK-079
    D.3.9.4EV Substance CodeSUB178418
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number100
    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 Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    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.2.1.2Country 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 namemetilprdnisolone
    D.3.2Product code [-]
    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 INNMETILPREDNISOLONE
    D.3.9.1CAS number 83-43-2
    D.3.9.2Current sponsor codemetilprednisolone
    D.3.9.3Other descriptive namemethylprednisolone
    D.3.9.4EV Substance CodeSUB08872MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number4
    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) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    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: 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.2.1.2Country 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 namedifenidramina
    D.3.2Product code [NA]
    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 INNDIFENIDRAMINA CLORIDRATO
    D.3.9.1CAS number 147-24-0
    D.3.9.2Current sponsor codedifenidramina clordirato
    D.3.9.3Other descriptive namediphenhydramine hydrochloride
    D.3.9.4EV Substance CodeSUB01769MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    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 Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    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: 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.2.1.2Country 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 nameparacetamolo
    D.3.2Product code [acetominofene]
    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 INNPARACETAMOLO
    D.3.9.1CAS number 103-90-2
    D.3.9.2Current sponsor codeparacetamolo
    D.3.9.3Other descriptive nameacetaminophen
    D.3.9.4EV Substance CodeSUB09611MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number500
    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 Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    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
    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
    Generalized Myasthenia Gravis
    Miastenia grave generalizzata
    E.1.1.1Medical condition in easily understood language
    The skeletal muscle weakness and fatigability worsens with physical
    activity and improves with rest
    La debolezza e l’affaticamento del muscolo scheletrico peggiora con l’attività fisica e migliora con il riposo
    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 21.1
    E.1.2Level PT
    E.1.2Classification code 10028417
    E.1.2Term Myasthenia gravis
    E.1.2System Organ Class 10029205 - Nervous system disorders
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To evaluate the safety and tolerability of TAK-079 in patients with generalized MG who are receiving stable background therapy for MG.
    Valutare la sicurezza e la tollerabilità di TAK-079 in pazienti affetti da MG generalizzata che ricevono una terapia di base stabile per la MG.
    E.2.2Secondary objectives of the trial
    To assess the effects of TAK-079 on MG disease activity using clinical rating scales and autoantibody levels.
    Valutare gli effetti di TAK-079 sull’attività della MG utilizzando scale di valutazione clinica e livelli di autoanticorpi.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Each patient must meet all the following inclusion criteria to be randomized to treatment:
    1. The patient understands and agrees to study participation by providing a signed and dated written informed consent form (ICF) and any required privacy authorization before the initiation of any study procedures (as applicable, the patient’s legally acceptable representative may provide written informed consent in accordance with local and regional regulatory requirements) and, in the opinion of the investigator, is capable of complying with protocol requirements.
    2. Aged 18 years or older.
    3. Diagnosis of MG supported by a positive serologic test for anti-AChR or anti-MuSK antibodies at screening.
    4. MGFA clinical classification class II to IV at screening.
    5. MG-ADL total score of 6 or greater at screening, with at least 4 points of this score attributed to nonocular items.
    6. If receiving immunosuppressive drugs (ie, mycophenolate mofetil, methotrexate, cyclosporine, tacrolimus, cyclophosphamide), therapy must be ongoing for at least 6 months, with a stable dosing ongoing for at least 3 months before screening. Patients receiving azathioprine must be on a stable dose for at least 6 months before screening.
    7. If receiving oral corticosteroids, therapy must be ongoing for at least 3 months, with a stable dose at least 1 month before screening. Corticosteroids, including dexamethasone, must be given as oral, daily or every-other-day therapy, as opposed to pulse therapy.
    8. If receiving cholinesterase inhibitors, therapy with a stable dose is required at least 2 weeks before screening.
    9. The doses of concomitant standard background therapy must be expected to remain stable throughout the study unless dose reduction is required due to toxicities. Allowed background therapy is defined as no more than a cholinesterase inhibitor ± corticosteroid ± one steroid-sparing immunosuppressive drug (limited to azathioprine, mycophenolate mofetil, methotrexate, cyclosporine, tacrolimus, or cyclophosphamide). Patients must be on at least one allowed background medication.
    10. Female patients of childbearing potential are required to have a negative pregnancy test. Both male and female patients must practice an effective, reliable and approved contraceptive regimen during the study and for up to 90 days or 5 half-lives, whichever is longer, after discontinuation of treatment.
    11. Patients must be able and willing to comply with study procedures.
    Ogni paziente deve soddisfare tutti i seguenti criteri di inclusione per essere randomizzato al trattamento:
    1. Il paziente comprende e accetta di partecipare allo studio fornendo un modulo di consenso informato (ICF) scritto firmato e datato e qualsiasi autorizzazione sulla privacy richiesta prima dell’inizio di qualsiasi procedura dello studio (come applicabile, il rappresentante legalmente accettabile del paziente può fornire il consenso informato scritto in conformità con i requisiti normativi locali e regionali) e, a giudizio dello sperimentatore, è in grado di rispettare i requisiti del protocollo.
    2. Età 18 anni o più.
    3. Diagnosi di MG supportata da un test sierologico positivo per gli anticorpi anti-AChR o anti-MuSK allo screening.
    4. Classificazione clinica della MGFA di classe da II a IV allo screening.
    5. Punteggio MG-ADL totale di 6 o superiore allo screening, con almeno 4 punti di tale punteggio attribuibile a elementi non oculari.
    6. In caso di trattamento con farmaci immunosoppressori (ad es., micofenolato mofetile, metotressato, ciclosporina, tacrolimus, ciclofosfamide), la terapia deve essere in corso da almeno 6 mesi, con con una somministrazione stabile in corso da almeno 3 mesi prima dello screening. I pazienti che ricevono azatioprina devono ricevere una dose stabile per almeno 6 mesi prima dello screening.
    7. In caso di trattamento con corticosteroidi orali, la terapia deve essere in corso da almeno 3 mesi, con una dose stabile da almeno 1 mese prima dello screening. I corticosteroidi, compreso il desametasone, devono essere somministrati come terapia orale, giornaliera o a giorni alterni, in contrapposizione alla pulsoterapia.
    8. In caso di trattamento con inibitori della colinesterasi, è richiesta una terapia con una dose stabile da almeno 2 settimane prima dello screening.
    9. Le dosi di terapia di base standard concomitante devono rimanere stabili per tutta la durata dello studio, a meno non sia richiesta una riduzione della dose a causa delle tossicità. La terapia di base consentita è definita come non più di un inibitore della colinesterasi ± corticosteroide ± un farmaco immunosoppressore che consente un risparmio degli steroidi (limitato a azatioprina, micofenolato mofetile, metotressato, ciclosporina, tacrolimus o ciclofosfamide). I pazienti devono riceve almeno un farmaco di base consentito.
    10. Le pazienti di sesso femminile in età fertile devono avere un test di gravidanza negativo. I pazienti sia di sesso femminile che maschile devono adottare un regime contraccettivo efficace, affidabile e approvato durante lo studio e fino a 90 giorni o 5 emivite, a seconda di quale periodo è più lungo, dopo l’interruzione del trattamento.
    11. I pazienti devono essere in grado e disposti a rispettare le procedure dello studio.
    E.4Principal exclusion criteria
    Patients meeting any of the following exclusion criteria are not to be randomized to treatment:
    1. History of thymoma or other thymic neoplasms.
    2. History of thymectomy within 12 months before screening.
    3. MGFA class I or V.
    4. Received IVIg, SCIg (subcutaneous immunoglobulin), or plasmapheresis/plasma exchange within 4 weeks before screening.
    5. Chronic obstructive pulmonary disease (COPD) or asthma with a pre-bronchodilatory forced expiratory volume in 1 second (FEV1) <50% of predicted normal.
    Note: FEV1 testing is required for patients suspected of having COPD or asthma.
    6. Received rituximab, belimumab, eculizumab, or any monoclonal antibody for immunomodulation within 6 months before first dosing. Patients with prior exposure to rituximab must have CD19 counts within the normal range at screening.
    Known autoimmune disease other than MG that would interfere with the course and conduct of the study.
    8. Received a live vaccine within 4 weeks before screening or has any live vaccination planned during the study.
    9. Any medical condition that, in the opinion of the investigator, might interfere with the patient’s participation in the study (such as significant cardiovascular, pulmonary, hematologic, gastrointestinal, endocrinologic, hepatic, renal, neurologic, malignancy, or infectious disease), poses added risk for the patient, or could confound the
    assessment of the patient.
    10. Pregnancy or lactation during the screening period or on Day 1 before first dose of study drug.
    11. Participation in any other investigational drug study or exposure to other investigational agent within 4 weeks or 5 half-lives, whichever is longer, before Day 1.
    12. An opportunistic infection =12 weeks before initial study dosing or is currently receiving treatment for a chronic opportunistic infection, such as tuberculosis (TB), pneumocystis pneumonia, cytomegalovirus, herpes simplex virus, herpes zoster, or atypical mycobacteria. A mild, localized herpes simplex infection within 12 weeks of study dosing is allowed, as long as the lesion has resolved without systemic therapy before Day 1.
    13. Inadequate organ and bone marrow function:
    a) Alanine aminotransferase or aspartate aminotransferase >3 times the upper limit of normal (ULN).
    b) Total bilirubin >1.5 times ULN (Note: Patients with a confirmed and documented diagnosis of Gilbert
    syndrome are not excluded based on this criterion).
    c) Platelets <75,000/mm3.
    d) Absolute neutrophil count <1500/mm3.
    e) Hemoglobin <8 g/dL.
    f) IgG less than 5 g/L (500 mg/dL).
    g) Lymphocyte count <500/mm3.
    14. A positive T-cell interferon-¿ release assay (TIGRA) (result through QuantiFERON-TB Gold test or T-Spot/Elispot) at the screening visit, noting the following:
    a) A purified protein derivative (PPD) skin test may be used if TIGRA testing is not available.
    b) Patients with an indeterminate TIGRA result must meet the following criteria:
    i. Negative PPD skin test (defined as <5 mm induration).
    ii. At low risk of acquiring TB (eg, avoids close contact with TB-positive individual[s]) and/or chest x-ray =6 months before the screening visit that is consistent with no evidence of latent or active TB.
    15. Any serious medical or psychiatric illness that could, in the investigator’s opinion, potentially interfere with the
    completion of treatment according to this protocol.
    16. A positive test result for hepatitis B surface antigen, or hepatitis B core antibody, hepatitis C antibody, or HIV antibody/antigen, at screening. However, an individual who has a known history of chronic hepatitis C and has been treated and fully cured of the disease, confirmed with a negative hepatitis C virus RNA polymerase chain reaction test at screening, is not excluded on the basis of positive hepatitis C antibody alone.
    17. A history of severe allergic or anaphylactic reactions to recombinant proteins or excipients used in the TAK-079/placebo formulation.
    I pz. che soddisfano uno qualsiasi dei seguenti criteri di esclusione non saranno randomizzati al trattamento:
    1. Anamnesi di timoma o altre neoplasie del timo.
    2. Anamnesi di timectomia nei 12 mesi precedenti lo screening.
    3. MGFA di classe I o V.
    4. Pz. che hanno ricevuto IVIg, SCIg (immunoglobuline per via sottocutanea) o plasmaferesi/scambio plasmatico entro 4 settimane prima dello screening.
    5. BPCO o asma con FEV1 < 50% del normale previsto. Nota: Il test FEV1 è richiesto per i pz.con sospetta BPCO o asma.
    6. Uso di rituximab, belimumab, aculizumab o di qualsiasi anticorpo monoclonale immunomodulante nei 6 mesi precedenti la prima somministrazione. I pz.con precedente esposizione a rituximab devono avere una conta di CD19 nel range normale allo screening.
    Nota malattia autoimmune diversa da MG che potrebbe interferire con lo svolgimento e la conduzione dello studio.
    8. ricevuto un vaccino vivo nelle 4 settimane precedenti lo screening o è prevista una vaccinazione viva durante lo studio.
    9. Qualsiasi condizione medica che, a giudizio del PI, potrebbe interferire con la partecipazione del pz.allo studio (come significativa patologia cardiovascolare, polmonare, ematologica, gastrointestinale, endocrinologica, epatica, renale, neurologica, neoplastica o infettiva), che comporta un rischio aggiuntivo per il pz.o potrebbe confondere la valutazione del pz..
    10. Gravidanza o allattamento durante il periodo di screening o il Giorno 1 prima della prima dose di farmaco sperim..
    11. Partecipazione a qualsiasi altro studio su un farmaco sperimentale oppure esposizione a un altro agente sperimentale nelle 4 settimane o 5 emivite, a seconda di quale periodo è più lungo, prima del Giorno 1.
    12. Infezione opportunistica = 12 sett. prima della somministrazione iniziale dello studio o attualmente sottoposto a trattamento per un’infezione opportunistica cronica, come tubercolosi (TB), polmonite da pneumocystis, citomegalovirus (CMV), virus dell’herpes simplex, herpes zoster o micobatteri atipici. È consentita un’infezione lieve e localizzata di herpes simplex nelle 12 settimane precedenti la somministrazione deli farmaco dello studio, a condizione che la lesione si sia risolta senza terapia sistemica prima del Giorno 1
    13. Funzione d’organo e del midollo osseo inadeguata:
    a) ALT o AST > 3 volte il limite superiore della norma (ULN).
    b) Bilirubina totale > 1,5 volte l’ULN (Nota: i pazienti con una diagnosi confermata e documentata di sindrome di Gilbert non sono esclusi in base a questo criterio).
    c) Piastrine < 75.000/mm3.
    d) Conta assoluta dei neutrofili < 1500/mm3.
    e) Emoglobina < 8 g/dl.
    f) IgG inferiore a 5 g/l (500 mg/dl
    g) Conta linfocitaria < 500/mm3.
    14. Un risultato positivo del test di rilascio di interferone- ¿ delle cellule T (TIGRA) (risultato tramite il test QuantiFERON-TB Gold o T Spot/Elispot) alla visita di screening, annotando quanto segue:
    a) Può essere utilizzato un test cutaneo con un derivato proteico purificato (PPD) se il test TIGRA non è disponibile.
    b) I pazienti con un risultato TIGRA indeterminato devono soddisfare i seguenti criteri:
    i. Un risultato negativo al test cutaneo PPD (definito come indurimento < 5 mm).
    ii. Un basso rischio di contrarre la TB (per es. evita uno stretto contatto con individui positivi alla TB) e/o radiografia del torace = 6 mesi prima della visita di screening che è coerente con l’assenza di qualsiasi evidenza di TB latente o attiva.
    15, 16, 17, Per l'elenco completo dei criteri di esclusione vedi protocollo di studio
    E.5 End points
    E.5.1Primary end point(s)
    Percentage of patients with TEAEs, including Grade 3 or higher events, SAEs, and AEs leading to TAK-079 discontinuation.
    Percentuale di pazienti con TEAE, inclusi eventi di Grado 3 o superiore, SAE ed eventi avversi che portano all’interruzione di TAK-079.
    E.5.1.1Timepoint(s) of evaluation of this end point
    TEAEs that occur after administration of the first dose of TAK-079 and through the end of the SFU period will be tabulated.
    I TEAE che si verificano dopo la somministrazione della prima dose di TAK-079 e fino al termine del periodo di SFU saranno riepilogati in tabelle.
    E.5.2Secondary end point(s)
    1. Score change from baseline in the following:
    a) MG Activities of Daily Living (MG-ADL) score.
    b) Quantitative Myasthenia Gravis (QMG) score.
    c) Myasthenia Gravis Composite (MGC) score.
    d) Revised 15-item Myasthenia Gravis Quality of Life scale (MG -QoL15r).
    2. Change from baseline in anti-AChR antibody or anti-MuSK antibody levels.
    3. The percentage of patients meeting minimal clinically important difference criteria in the respective MG clinical impairment scales (MG-ADL, QMG, MGC, MG-QoL15r).
    1. Variazione del punteggio rispetto al basale in:
    a) Punteggio delle attività della vita quotidiana nella MG (MG-ADL).
    b) Punteggio quantitativo per la miastenia gravis (QMG).
    c) Punteggio composito della miastenia gravis (MGC).
    d) Scala della qualità della vita per la miastenia gravis revisionata a 15 voci (MG -QoL15r).
    2. Variazione rispetto al basale nei livelli dell’anticorpo anti-AChR o anti-MuSK.
    3. Percentuale dei pazienti che soddisfano i criteri di differenza minima clinicamente importante nelle rispettive scale di insufficienza clinica della MG (MG-ADL, QMG, MGC, MG-QoL15r).
    E.5.2.1Timepoint(s) of evaluation of this end point
    Throughout the study. Please refer to protocol Appendix A Schedule of Events
    Per tutta la durata dello studio. La preghiamo di fare riferimento all’Appendice A Programmazione degli eventi del protocollo
    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 Yes
    E.6.7Pharmacodynamic Yes
    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 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 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 concerned5
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA17
    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 Information not present in EudraCT
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Canada
    Italy
    Poland
    Serbia
    Spain
    United States
    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
    The analyses for the clinical study report will be conducted after all patients randomized in the study have completed the end-of-study visit (ie, Week 20 for placebo patients or Week 32 for TAK-079 patients)
    Le analisi per il Clinical Study Report saranno condotte dopo che tutti i pazienti randomizzati nello studio avranno completato la visita di fine studio (ossia, Settimana 20 per i pazienti trattati con placebo o Settimana 32 per i pazienti trattati con TAK-079)
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years0
    E.8.9.1In the Member State concerned months9
    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 months9
    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: 25
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 11
    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 Yes
    F.3.3.6.1Details of subjects incapable of giving consent
    If the patient is not capable of rendering adequate written informed
    consent, the patient's legally acceptable representative may provide
    such consent for the patient in accordance with applicable laws and
    regulations
    Se il paziente non è in grado di fornire un consesno informato scritto, il rappresentante legalmente accettato del paziente
    può fornire tale consenso per il paziente in conformità con le leggi e la normativa applicabili
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state10
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 16
    F.4.2.2In the whole clinical trial 36
    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)
    End of SFP clinical parameters (Protocol section 9.6 End of SFP assessment) will be assessed at Week 16 of the SFP. If clinical presentation and parameters do not meet the end of SFP criteria, and are deemed by the principal investigator as study related, the study-related parameters not meeting end-of-study criteria will continue to be assessed in the LFP until they normalize or return to baseline.
    I parametri clinici di fine SFP (Protocollo sezione 9.6 valutazione di fine SFP) saranno valutati alla Settimana 16 del SFP. Se la presentazione clinica e i parametri non soddisfano i criteri di fine SFP e sono ritenuti dallo sperimentatore principale come correlati allo studio, i parametri correlati allo studio che non soddisfano i criteri di fine studio continueranno a essere valutati nel LFP fino a quando non si normalizzano o ritorno al valore basale.
    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 Decision2020-08-12
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2020-05-06
    P. End of Trial
    P.End of Trial StatusOngoing
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