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    Summary
    EudraCT Number:2020-002915-23
    Sponsor's Protocol Code Number:ARGX-113-1904
    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:2021-05-24
    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 number2020-002915-23
    A.3Full title of the trial
    A Randomized, Double-Blinded, Placebo-Controlled Trial to Investigate the Efficacy, Safety, and Tolerability of Efgartigimod PH20 SC in Adult Patients With Pemphigus (Vulgaris or Foliaceus) (ADDRESS)
    Studio randomizzato, in doppio cieco, controllato con placebo per valutare l’efficacia, la sicurezza e la tollerabilità di efgartigimod PH20 SC in pazienti adulti con pemfigo (volgare o foliaceo) (ADDRESS).
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A study to assess the safety and efficacy of a subcutaneous formulation of efgartigimod PH20 SC in adults with Pemphigus (Vulgaris or Foliaceus)
    Studio per valutare la sicurezza e l’efficacia di una formulazione sottocutanea di efgartigimod PH20 - negli adulti affetti da pemfigo (volgare o foliaceo)
    A.3.2Name or abbreviated title of the trial where available
    ADDRESS
    ADDRESS
    A.4.1Sponsor's protocol code numberARGX-113-1904
    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 SponsorARGENX BV
    B.1.3.4CountryBelgium
    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 supportargenx BV
    B.4.2CountryBelgium
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationargenx BV
    B.5.2Functional name of contact pointRegulatory
    B.5.3 Address:
    B.5.3.1Street AddressIndustriepark Zwijnaarde 7
    B.5.3.2Town/ cityZwijnaarde
    B.5.3.3Post codeB-9052
    B.5.3.4CountryBelgium
    B.5.4Telephone number003293103400
    B.5.5Fax number000000
    B.5.6E-mailregulatory@argenx.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 Yes
    D.2.1.1.1Trade name Prednison 50 mg GALEN
    D.2.1.1.2Name of the Marketing Authorisation holderGALENpharma GmbH
    D.2.1.2Country which granted the Marketing AuthorisationGermany
    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 namena
    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 INNPREDNISONE
    D.3.9.1CAS number 53-03-2
    D.3.9.2Current sponsor codena
    D.3.9.3Other descriptive namePREDNISONE
    D.3.9.4EV Substance CodeSUB10020MIG
    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 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: 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 Prednison 5 mg GALEN
    D.2.1.1.2Name of the Marketing Authorisation holderGALENpharma GmbH
    D.2.1.2Country which granted the Marketing AuthorisationGermany
    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 namena
    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 INNPREDNISONE
    D.3.9.1CAS number 53-03-2
    D.3.9.2Current sponsor codena
    D.3.9.3Other descriptive nameprednisone
    D.3.9.4EV Substance CodeSUB10020MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number5
    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: 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 Prednison20 mg GALEN
    D.2.1.1.2Name of the Marketing Authorisation holderGALENpharma GmbH
    D.2.1.2Country which granted the Marketing AuthorisationGermany
    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 namena
    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 INNPREDNISONE
    D.3.9.1CAS number 53-03-2
    D.3.9.2Current sponsor codena
    D.3.9.3Other descriptive namePREDNISONE
    D.3.9.4EV Substance CodeSUB10020MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number20
    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 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 nameEfgartigimod PH20 SC
    D.3.2Product code [na]
    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 INNEFGARTIGIMOD ALFA
    D.3.9.1CAS number 1821402-21-4
    D.3.9.2Current sponsor code1821402-21-4
    D.3.9.4EV Substance CodeSUB180001
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number165
    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: 5
    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 Prednison 10 mg GALEN
    D.2.1.1.2Name of the Marketing Authorisation holderGALENpharma GmbH
    D.2.1.2Country which granted the Marketing AuthorisationGermany
    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 namena
    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 INNPREDNISONE
    D.3.9.1CAS number 53-03-2
    D.3.9.2Current sponsor codena
    D.3.9.3Other descriptive namePREDNISONE
    D.3.9.4EV Substance CodeSUB10020MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    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 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
    Pemphigus Vulgaris or Pemphigus Foliaceus
    pemfigo volgare o foliaceo
    E.1.1.1Medical condition in easily understood language
    Blistering autoimmune diseases that affect the skin and mucous membranes
    Malattie autoimmuni con formazione di vesciche che interessano la pelle e le membrane mucose
    E.1.1.2Therapeutic area Diseases [C] - Immune System Diseases [C20]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10057069
    E.1.2Term Pemphigus foliaceus
    E.1.2System Organ Class 100000004858
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10052802
    E.1.2Term Pemphigus vulgaris
    E.1.2System Organ Class 100000004858
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To demonstrate the efficacy of efgartigimod PH20 SC compared to placebo in the treatment of patients with Pemphigus vulgaris
    Dimostrare l’efficacia di efgartigimod PH20 SC rispetto al placebo nel trattamento di pazienti affetti da PV
    E.2.2Secondary objectives of the trial
    • To demonstrate the efficacy of efgartigimod PH20 SC in the treatment of patients with pemphigus vulgaris or pemphigus foliaceus
    • To assess the safety of efgartigimod PH20 SC in patients with PV or PF
    • To evaluate the effects of efgartigimod PH20 SC on quality of life (QoL) in patients with PV or PF
    • To evaluate the PK of efgartigimod PH20 SC in patients with PV or PF
    • To evaluate the PD of efgartigimod PH20 SC in patients with PV or PF
    • To evaluate the immunogenicity of efgartigimod PH20 SC in patients with PV or PF
    • Dimostrare l’efficacia di efgartigimod PH20 SC nel trattamento di pazienti affetti da PV o da PF
    • Valutare la sicurezza di efgartigimod PH20 SC nei pazienti affetti da PV o da PF
    • Valutare gli effetti di efgartigimod PH20 SC sulla qualità della vita (Quality Of Life, [QoL]) nei pazienti affetti da PV o PF
    • Valutare la PK di efgartigimod PH20 SC nei pazienti affetti da PV o PF
    • Valutare la PD di efgartigimod PH20 SC nei pazienti affetti da PV o PF
    • Valutare l’immunogenicità di efgartigimod PH20 SC nei pazienti affetti da PV o da PF
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives

    Other types of substudies
    Specify title, date and version of each substudy with relative objectives: Evaluation of biomarkers of pemphigus pathology from skin biopsis

    Altre tipologie di sottostudi
    specificare il titolo, la data e la versione di ogni sottostudio con i relativi obiettivi: Valutazione dei biomarcatori della patologia del pemfigo tramite biopsie cutanee
    E.3Principal inclusion criteria
    1. Ability to understand the requirements of the trial, to provide written informed consent (including consent for the use and disclosure of research-related health information), willingness and ability to comply with the trial protocol procedures (including required trial visits).
    2. The patient is male or female, and aged 18 years to 80 years at the time of signing the informed consent form (ICF).
    3. The patient has a clinical diagnosis of PV (mucosal, cutaneous, mucocutaneous) or PF which has been confirmed by cutaneous histology, positive direct immunofluorescence (IF), and positive indirect IF and/or ELISA.
    4. The patient meets 1 of the following profiles:
    a. Newly diagnosed disease with PDAI =15 at baseline and naïve to treatment.
    b. Newly diagnosed disease with PDAI =15 while receiving a first course of oral prednisone (or equivalent). According to clinical judgment, the patient has shown no significant improvement of PV or PF signs for at least 2 weeks before baseline and is considered fit to start prednisone
    treatment at 0.5 mg/kg qd at baseline.
    c. Experiencing flare with PDAI =15, a maximum of 4 years since diagnosis, and off prednisone therapy ± a conventional immunosuppressant (eg, azathioprine, cyclophosphamide, methotrexate, mycophenolate mofetil). Note: conventional immunosuppressants must be discontinued before baseline.
    d. Experiencing flare with PDAI =15, a maximum of 4 years since diagnosis, and receiving a tapered dose of oral prednisone (or equivalent), provided that prednisone has been given at stable dose ± a conventional immunosuppressant (eg, azathioprine, cyclophosphamide, methotrexate, mycophenolate mofetil) for at least 2 weeks and patients are fit to start prednisone treatment at 0.5 mg/kg qd at baseline. Note: conventional
    immunosuppressants must be discontinued before baseline.
    5. Women of childbearing potential:
    a. Must have a negative serum pregnancy test at screening and a negative urine pregnancy test at baseline before trial medication can be
    administered.
    b. Must be on a stable regimen for at least 1 month of at least 1 highly effective method of contraception (ie, failure rate of less than 1% per year) during the trial and for 90 days after the last administration of IMP.
    6. Non-sterilized male patients who are sexually active with a female partner of childbearing potential must use effective contraception from first administration of IMP through 90 days after the last administration of the IMP. Male patients practicing true sexual abstinence (as consistent with preferred and usual life style) can be included. Sterilized male patients who have had a vasectomy and with documented absence of sperm post-procedure can be included. Male patients are not allowed to donate sperm from first administration of IMP through 90 days after the last dose of IMP.

    1. Capacità di comprendere i requisiti della sperimentazione, fornire un consenso informato scritto (compreso il consenso per l’utilizzo e la divulgazione di informazioni sanitarie correlate alla ricerca), volontà e capacità di attenersi alle procedure del protocollo di sperimentazione (comprese le visite obbligatorie dello studio).
    2. Il paziente può essere di sesso maschile o femminile e deve avere un’età compresa tra 18 anni e 80 anni al momento della firma del modulo di consenso informato (Informed Consent Form, [ICF]).
    3. Il paziente ha una diagnosi clinica di PV (mucosale, cutaneo o mucocutaneo) o di PF, che è stata confermata da istologia cutanea, immunofluorescenza diretta (IF) e IF indiretta con esito positivo e/o saggio di immunoassorbimento enzimatico (Enzyme-Linked Immunosorbent Assay, [ELISA]) positivo.
    4. Il paziente soddisfa 1 dei seguenti profili:
    a. È affetto da malattia di nuova diagnosi con punteggio di attività PDAI =15 (vedere Sezione 10.8) al basale e naïve al trattamento.
    b. È affetto da malattia di nuova diagnosi con punteggio di attività PDAI =15 durante la somministrazione di un primo ciclo di prednisone orale (o equivalente). In base al giudizio clinico, il paziente non ha mostrato alcun miglioramento significativo dei segni di PV o PF per almeno 2 settimane prima del basale ed è considerato idoneo a iniziare il trattamento con prednisone a 0,5 mg/kg una volta al giorno al basale.
    c. Manifesta una riacutizzazione con punteggio di attività PDAI =15 a un massimo di 4 anni dalla diagnosi e dopo terapia con prednisone ± terapia immunosoppressiva convenzionale (per es., azatioprina, ciclofosfamide, metotrexato, micofenolato mofetile). Nota: gli immunosoppressori convenzionali devono essere interrotti prima della visita basale.
    d. Manifesta una riacutizzazione con punteggio di attività PDAI =15 a un massimo di 4 anni dalla diagnosi e riceve una dose di prednisone orale ridotta gradualmente (o equivalente), a condizione che il prednisone sia stato somministrato in dose stabile ± un immunosoppressore convenzionale (per es., azatioprina, ciclofosfamide, metotrexato, micofenolato mofetile) per almeno 2 settimane e che il paziente sia idoneo a iniziare un trattamento con prednisone a 0,5 mg/kg una volta al giorno al basale. Nota: gli immunosoppressori convenzionali devono essere interrotti prima del basale.
    5. Donne in età fertile (vedere definizione nella Sezione 10.5):
    a. Prima che il farmaco sperimentale possa essere somministrato, devono avere un test di gravidanza sul siero negativo allo screening e un test di gravidanza sulle urine negativo alla visita al basale.
    b. Devono seguire un regime stabile da almeno 1 mese con almeno 1 metodo contraccettivo altamente efficace (vale a dire tasso di fallimento inferiore all’1% annuo; vedere Metodi contraccettivi femminili altamente efficaci nella Sezione 10.5) durante la sperimentazione e per 90 giorni dopo l’ultima somministrazione di IMP.
    6. I pazienti di sesso maschile non sterilizzati, che sono sessualmente attivi con una partner di sesso femminile in età fertile, devono usare un metodo contraccettivo efficace dalla prima somministrazione dell’IMP fino a 90 giorni dopo l’ultima somministrazione dell’IMP. Potranno essere inclusi i pazienti di sesso maschile che pratichino realmente l’astinenza sessuale (se ciò è in linea con lo stile di vita preferito e abituale del partecipante). Potranno essere inclusi i pazienti di sesso maschile sterilizzati sottoposti a vasectomia e con aspermia post-procedurale documentata. Inoltre, ai pazienti di sesso maschile non sarà consentito donare lo sperma a partire dalla prima somministrazione dell’IMP e per 90 giorni dopo l’ultima dose di IMP.
    E.4Principal exclusion criteria
    1. Patient has a confirmed diagnosis of paraneoplastic pemphigus, drug-induced pemphigus, pemphigus vegetans, pemphigus erythematosus, or any other non-PV/non-PF autoimmune blistering disease.
    2. Patients with mild disease severity as defined by PDAI <15 at baseline.
    3. Patients who show a significant improvement of PV or PF in the period from screening to baseline according to clinical judgment (eg, the patient has achieved DC or a substantial reduction in PDAI activity score during screening period).
    4. The patient has been administered therapy other than oral prednisone or conventional immunosuppressants (eg, azathioprine, cyclophosphamide, methotrexate, mycophenolate mofetil) within 2 months before the baseline visit and that can affect clinical disease activity.
    5. Use of any monoclonal antibody (including rituximab or another anti-CD20 biologic) within 6 months before the baseline visit.
    6. Known hypersensitivity to any of the components of the administered treatments.
    7. The patient has a known contraindication to oral prednisone.
    8. The patient has a history of refractory disease, as defined by a failure to respond to first-line and second-line therapies.
    9. Patients who have a history of malignancy unless deemed cured by adequate treatment with no evidence of recurrence for =3 years before first IMP administration. Patients with any of the following cancers can be included at any time:
    a. Adequately treated basal cell or squamous cell skin cancer
    b. Carcinoma in situ of the cervix
    c. Carcinoma in situ of the breast
    d. Incidental histological finding of prostate cancer (TNM stage T1a or T1b)
    10. Patients with clinical evidence of other significant serious disease or patients who recently underwent or have planned a major surgery during the period of the trial, or any other condition in the opinion of the investigator, that could confound the results of the trial or put the patient at undue risk.
    11. Pregnant and lactating women and those intending to become pregnant during the trial or within 90 days after the last administration of IMP.
    12. Current or history (ie, within 12 months of screening) of alcohol, drug, or medication abuse.
    13. Any other known autoimmune disease that, in the opinion of the investigator, would interfere with an accurate assessment of clinical symptoms of PV or PF or put the participant at undue risk.
    14. The patient has a Karnofsky performance score <60%.
    15. Vaccination with live/attenuated viral vaccines within 28 days prior to randomization.
    16. The patient has clinically significant uncontrolled active or chronic bacterial, viral, or fungal infection.
    17. Positive serum test at screening for an active viral infection with any of the following conditions:
    a. Hepatitis B Virus (HBV)
    b. Hepatitis C Virus (HCV)
    c. Human immunodeficiency virus (HIV)
    18. The patient has total immunoglobulin G (IgG) <6 g/L at screening.
    19. The patient has previously participated in a trial with efgartigimod and has received at least 1 administration of IMP.
    20. Use of an investigational drug within 3 months or 5 half-lives of the drug (whichever is longer) prior to first IMP administration.
    1. Paz. ha diagnosi confermata di pemfigo paraneoplastico, indotto da farmaci, vegetans, eritematoso o qualsiasi altra malattia autoimmune non-PV/non-PF che comporti la formazione di vesciche.
    2.Paz. ha gravità della malattia lieve secondo un punteggio di attività PDAI <15 al basale.
    3. Paz. che mostrano un miglioramento significativo del PV o PF nel periodo di tempo che va dallo screening al basale in base al giudizio clinico (ad es., il paz. ha raggiunto il DC o una sostanziale riduzione del punteggio di attività PDAI durante il periodo di screening).
    4.Al paz. sono state somministrate terapie diverse da prednisone orale o immunosoppressori convenzionali (es. azatioprina, ciclofosfamide, metotrexato, micofenolato mofetile) entro 2 mesi prima della visita basale, che possono incidere sull’attività clinica della malattia. Per es. i farmaci esclusi sono il metilprednisolone per via endovenosa, il dapsone, la sulfasalazina, la tetraciclina, la nicotinamide, la plasmaferesi/la trasfusione di plasma, l’immunoadsorbimento e l’IVIg. Nota: gli immunosoppressori convenzionali devono essere interrotti prima del basale.
    5.Uso di anticorpi monoclonali (compreso rituximab o un altro farmaco biologico anti-CD20) entro 6 mesi prima della visita basale.
    6.Ipersensibilità nota a qualsiasi dei componenti dei trattamenti somministrati.
    7. Paz. ha controindicazione nota per il prednisone orale.
    8. Paz. ha un’anamnesi di malattia refrattaria, come definita da mancata risposta alle terapie di prima e seconda linea.
    9. Paz. ha un’anamnesi di neoplasia maligna, a meno che non sia considerato guarito mediante una terapia adeguata e senza evidenze di recidiva per =3 anni prima della prima somministrazione dell’IMP. Potranno essere inclusi in qualsiasi momento i pazienti con i seguenti tumori maligni:
    a. Tumore cutaneo basocellulare o squamocellulare adeguatamente trattato
    b. Carcinoma della cervice uterina in situ
    c. Carcinoma mammario in situ
    d. Reperto istologico casuale di tumore prostatico (stadio TNM T1a o T1b)
    10. Paz. con evidenza clinica di altra malattia significativa grave o i pazienti sottoposti di recente, o candidati, a intervento di chirurgia maggiore durante il periodo della sperimentazione o qualsiasi altra condizione che a giudizio dello sperimentatore potrebbe confondere i risultati della sperimentazione o comporterebbe un rischio eccessivo per il paziente.
    11.Le donne incinte e in fase di allattamento al seno e quelle che intendono rimanere incinte durante la sperimentazione o entro i 90 giorni successivi all’ultima somministrazione dell’IMP.
    12.Anamnesi attuale o pregressa (ovvero, entro 12 mesi dallo screening) di abuso di alcol, farmaci o sostanze stupefacenti.
    13.Qualsiasi altra malattia autoimmune nota che, a giudizio dello sperimentatore, interferirebbe con una valutazione accurata dei sintomi clinici di PV o PF o esporrebbe il partecipante a un rischio inopportuno.
    14.Il paz. con punteggio di validità di Karnofsky <60%.
    15.Vaccinazione con vaccini virali vivi/attenuati entro 28 giorni prima della randomizzazione.
    16.Il paz. presenta infezione batterica, virale o fungina clinicamente significativa, attiva o cronica non controllata.
    17.Positività del test sierico per una infezione virale attiva allo screening con una qualsiasi delle seguenti condizioni:
    a.Virus HBV indicativo di un’infezione acuta o cronica (https://www.cdc.gov/hepatitis/HBV/PDFs/SerologicChartv8.pdf; V. Sezione 10.10).
    b.Virus HCV in base al test degli anticorpi anti-HCV.
    c.Virus HIV in base ai risultati del test che sono associati a una condizione che definisce la AIDS o una conta CD4 <200 cellule/mm3.
    18.Il paz. presenta livelli di IgG tot <6 g/l allo screening.
    19.Il paz. ha precedentemente partecipato a uno studio clinico con efgartigimod e ha ricevuto almeno 1 somministrazione dell’IMP.
    20.Uso di farmaco sperimentale nei 3 mesi o nelle 5 emivite del farmaco (a seconda di quale sia il periodo più lungo) precedenti alla prima somministrazione dell’IMP.
    E.5 End points
    E.5.1Primary end point(s)
    Proportion of Pemphigus vulgaris patients who achieve complete clinical remission (CR) on minimal prednisone therapy within 30 weeks
    Percentuale di pazienti con PV che raggiungono la CR con terapia minima entro 30 settimane
    E.5.1.1Timepoint(s) of evaluation of this end point
    week 30
    30 settimane
    E.5.2Secondary end point(s)
    1. Proportion of PV and PF patients who achieve complete clinical CR on minimal prednisone therapy within 30 weeks
    2. Time to Disease Control (DC) in PV patients
    3. Time to CR in PV patients
    4. Cumulative prednisone dose over the trial in PV patients
    5. Time to DC in PV and PF patients
    6. Time to complete CR in PV and PF patients
    7. Cumulative prednisone dose over the trial in PV and PF patientss
    8. Rate of treatment failure
    9. Rate of flare
    10. PDAI at each visit
    11. Incidence and severity of TEAEs, AESIs, and SAEs by System Organ Class (SOC) and Preferred Term (PT).
    12. EuroQol Five-Dimension Five-Level Scale (EQ-5D-5L) score - 30 weeks treatment period
    13. Autoimmune Bullous Quality of Life (ABQOL) score
    14. Efgartigimod serum concentrations
    15. Total IgG and subtype (IgG1, IgG2, IgG3, IgG4) serum levels
    16. Anti Dsg-1 and -3 autoantibodies serum levels
    17. Anti-drug antibodies (ADA) to efgartigimod PH20 SC
    • Percentuale di pazienti con PV e PF che ottengono la CR con terapia minima entro 30 settimane
    • Tempo alla CR nei pazienti con PV
    • Tempo al DC nei pazienti con PV
    • Dose cumulativa di prednisone nel corso della sperimentazione nei pazienti con PV
    • Tempo al DC nei pazienti con PV e PF
    • Tempo alla CR nei pazienti con PV e PF
    • Dose cumulativa di prednisone nel corso della sperimentazione nei pazienti con PV e PF
    • Tasso di insuccesso del trattamento
    • Tasso di riacutizzazione
    • PDAI a ogni visita
    • Incidenza e gravità di TEAE, AESI e SAE in base alla classificazione per sistemi e organi (SOC) e termine preferito (PT)
    • Punteggio del Questionario europeo sulla qualità della vita a 5 dimensioni e 5 livelli (EuroQol 5-Dimension 5-Level, [EQ-5D-5L]) - Periodo di trattamento di 30 settimane
    • Punteggio del Questionario sulla qualità della vita per malattie bollose autoimmuni (Autoimmune Bullous Quality Of Life, [ABQOL])
    • Concentrazioni sieriche di efgartigimod
    • Livelli sierici di IgG totale e sottotipo (IgG1, IgG2, IgG3, IgG4)
    • Livelli sierici di autoanticorpi anti-Dsg-1 e -3
    • Anticorpi anti-farmaco (Anti-Drug Antibody, [ADA]) per efgartigimod (livelli sierici) e rHuPH20 (livelli plasmatici)
    E.5.2.1Timepoint(s) of evaluation of this end point
    endpoint 1: 30 weeks treatment period
    endpoints 2 to 9; up to 30 weeks
    endpoint 10 & 11: up to 41 weeks
    endpoint 12 & 13: 30 weeks treatment period
    endpoint 14: up to 38 weeks
    endpoint 15 & 16: up to 41 weeks
    endpoint 17: Up to 38 weeks
    endpoint 1: periodo di trattamento di 30 settimane
    endpoint da 2 a 9; massimo 30 settimane
    endpoint 10 e 11: massimo 41 settimane
    endpoint 12 e 13: periodo di trattamento di 30 settimane
    endpoint 14: massimo 38 settimane
    endpoint 15 e 16: massimo 41 settimane
    endpoint 17: massimo 38 settimane
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic 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 Yes
    E.6.13.1Other scope of the trial description
    Immunogenicity
    Immunogenicità
    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 No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    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 EEA51
    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
    Australia
    Bulgaria
    France
    Georgia
    Germany
    Greece
    Hungary
    India
    Israel
    Italy
    Japan
    Poland
    Romania
    Russian Federation
    Spain
    Turkey
    Ukraine
    United Kingdom
    United States
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    For the complete study, the end of the study is defined as last participant last visit in trial ARGX 113-1904
    Per il completamento dello studio, la fine dello studio è definita come l’ultima visita dell’ultimo partecipante nella sperimentazione ARGX 113-1904
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years1
    E.8.9.1In the Member State concerned months9
    E.8.9.1In the Member State concerned days28
    E.8.9.2In all countries concerned by the trial years1
    E.8.9.2In all countries concerned by the trial months9
    E.8.9.2In all countries concerned by the trial days28
    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: 105
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 4
    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 state25
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 100
    F.4.2.2In the whole clinical trial 150
    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)
    Under certain conditions described in the protocol, the patients may be eligible to roll over to the open-label extension trial ARGX-113-1905. For patients, randomized to the efgartigimod PH20 SC or placebo treatment arm in ARGX-113-1904, trial ARGX-113-1905 provides extended or first treatment and re-treatment options in the respective treatment arms. argenx is currently assessing the appropriateness and possibility of making efgartigimod PH20 SC available for trial participants post-trial.
    In det condizioni descritte nel protocollo, i paz potrebbero essere idonei a passare allo studio di estensione in aperto ARGX-113-1905. Per i paz, randomizzati a efgartigimod PH20 SC o con placebo nello studio ARGX-113-1904, la speri. ARGX-113-1905 fornisce opzioni di trattamento prolungato o primo trattamento e ri-trattamento nei rispettivi bracci. Argenx sta valutando l'appropriatezza e la possibilità di rendere efgartigimod PH20 SC disponibile ai partecipanti alla speri. dopo la stessa.
    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 Decision2020-12-11
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2020-10-06
    P. End of Trial
    P.End of Trial StatusOngoing
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