Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register allows you to search for protocol and results information on:
  • interventional clinical trials that are conducted in the European Union (EU) and the European Economic Area (EEA);
  • clinical trials conducted outside the EU / EEA that are linked to European paediatric-medicine development.
  • Learn   more about the EU Clinical Trials Register   including the source of the information and the legal basis.


    The EU Clinical Trials Register currently displays   42567   clinical trials with a EudraCT protocol, of which   7008   are clinical trials conducted with subjects less than 18 years old.
    The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).


    Phase 1 trials conducted solely in adults and that are not part of an agreed PIP are not public in the EU CTR (refer to European Guidance 2008/C 168/02   Art. 3 par. 2 and   Commission Guideline 2012/C 302/03,   Art. 5) .

    Clinical Trials marked as "Trial now transitioned" were transitioned to the Clinical Trial Regulation 536/2014 and can be further followed in the Clinical Trial Information System  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Print Download

    Summary
    EudraCT Number:2020-003272-41
    Sponsor's Protocol Code Number:R3918-MG-2018
    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:2021-10-19
    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 number2020-003272-41
    A.3Full title of the trial
    Efficacy and Safety of Pozelimab and Cemdisiran Combination Therapy in Patients with Symptomatic Generalized Myasthenia Gravis
    Efficacia e sicurezza della terapia combinata di pozelimab e cemdisiran in pazienti con miastenia gravis generalizzata sintomatica
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A study to examine the efficacy and safety of pozelimab and cemdisiran combination therapy in patients with symptomatic Generalized Myasthenia Gravis
    Studio per valutare efficacia e sicurezza della terapia combinata di pozelimab e cemdisiran in pazienti con miastenia gravis generalizzata sintomatica
    A.3.2Name or abbreviated title of the trial where available
    Study of Pozelimab and Cemdisiran combination therapy in patients with Myasthenia Gravis
    Studio della terapia di combinazione Pozelimab e Cemdisiran in pazienti con Miastenia Gravis
    A.4.1Sponsor's protocol code numberR3918-MG-2018
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT05070858
    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 SponsorREGENERON 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 supportRegeneron Pharmaceuticals, Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationRegeneron Pharmaceuticals, Inc.
    B.5.2Functional name of contact pointClinical Trial Information
    B.5.3 Address:
    B.5.3.1Street Address777 Old Saw Mill River Road
    B.5.3.2Town/ cityTarrytown
    B.5.3.3Post code10591
    B.5.3.4CountryUnited States
    B.5.6E-mailclinicaltrials@regeneron.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 nameCemdisiran
    D.3.2Product code [ALN-CC5]
    D.3.4Pharmaceutical form Solution for injection/infusion
    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 INNCemdisiran
    D.3.9.2Current sponsor codeALN-CC5
    D.3.9.4EV Substance CodeSUB217110
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number200
    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 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 namePozelimab
    D.3.2Product code [REGN3918]
    D.3.4Pharmaceutical form Solution for injection/infusion
    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 INNPozelimab
    D.3.9.2Current sponsor codeREGN3918
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number200
    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: 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 Bexsero
    D.2.1.1.2Name of the Marketing Authorisation holderGSK Vaccines S.r.l., Via Fiorentina 1, 53100 Siena, Italy EU/1/12/812/001-004
    D.2.1.2Country which granted the Marketing AuthorisationItaly
    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 nameBexsero
    D.3.2Product code [NA]
    D.3.4Pharmaceutical form Suspension for injection in pre-filled syringe
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntramuscular use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNOuter membrane vesicles (OMV) from Neisseria meningitidis group B strain NZ98/254measured as amount of total protein containing the PorA P1.4
    D.3.9.2Current sponsor codeN/A
    D.3.9.3Other descriptive nameRECOMBINANT NEISSERIA MENINGITIDIS GROUP B FHBP FUSION PROTEIN PRODUCED IN E.COLI CELLS BY RECOMBINANT DNA TECHNOLOGY ADSORBED ON ALUMINIUM HYDROXIDE
    D.3.9.4EV Substance CodeSUB96090
    D.3.10 Strength
    D.3.10.1Concentration unit µg microgram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number25
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNRECOMBINANT NEISSERIA MENINGITIDIS GROUP B NHBA FUSION PROTEIN
    D.3.9.2Current sponsor codeN/A
    D.3.9.3Other descriptive nameRECOMBINANT NEISSERIA MENINGITIDIS GROUP B NHBA FUSION PROTEIN
    D.3.9.4EV Substance CodeSUB191635
    D.3.10 Strength
    D.3.10.1Concentration unit µg microgram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number50
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNRECOMBINANT NEISSERIA MENINGITIDIS GROUP B NADA PROTEIN
    D.3.9.2Current sponsor codeN/A
    D.3.9.3Other descriptive nameRECOMBINANT NEISSERIA MENINGITIDIS GROUP B NADA PROTEIN
    D.3.9.4EV Substance CodeSUB191633
    D.3.10 Strength
    D.3.10.1Concentration unit µg microgram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number50
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNRECOMBINANT NEISSERIA MENINGITIDIS GROUP B FHBP FUSION PROTEIN
    D.3.9.2Current sponsor codeN/A
    D.3.9.3Other descriptive nameRECOMBINANT NEISSERIA MENINGITIDIS GROUP B FHBP FUSION PROTEIN
    D.3.9.4EV Substance CodeSUB191634
    D.3.10 Strength
    D.3.10.1Concentration unit µg microgram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number50
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product 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) 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: 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 Augmentin
    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 nameAugmentin 875 mg/125 mg
    D.3.2Product code [N/A]
    D.3.4Pharmaceutical form Film-coated 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 INNAMOXICILLINA
    D.3.9.2Current sponsor codeN/A
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number875
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNACIDO CLAVULANICO
    D.3.9.2Current sponsor codeN/A
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    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 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: 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 Menveo
    D.2.1.1.2Name of the Marketing Authorisation holderGSK Vaccines S.r.l. Italy EU/1/10/614-002-003
    D.2.1.2Country which granted the Marketing AuthorisationItaly
    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 nameMenveo
    D.3.2Product code [N/A]
    D.3.4Pharmaceutical form Powder and suspension for suspension for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntramuscular use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNMENINGOCOCCAL GROUP A OLIGOSACCHARIDES CONJUGATED TO CORYNEBACTERIUM DIPHTHERIAE C7(ß197) M8 (CRM197) PROTEIN
    D.3.9.2Current sponsor codeN/A
    D.3.9.3Other descriptive nameMENINGOCOCCAL GROUP A OLIGOSACCHARIDES CONJUGATED TO CORYNEBACTERIUM DIPHTHERIAEC7 (ß197) M8 (CRM197) PROTEIN
    D.3.9.4EV Substance CodeSUB77061
    D.3.10 Strength
    D.3.10.1Concentration unit µg microgram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNN. MENINGITIDIS GROUP C (STRAIN C11) OLIGOSACCHARIDE CONJUGATED TO CORYNEBACTERIUMDIPHTHERIAE CRM197 ADSORBED ON ALUMINUM HYDROXIDE
    D.3.9.2Current sponsor codeN/A
    D.3.9.3Other descriptive nameN. MENINGITIDIS GROUP C (STRAIN C11) OLIGOSACCHARIDE CONJUGATED TOCORYNEBACTERIUM DIPHTHERIAE CRM197 ADSORBED ON ALUMINUM HYDROXIDE
    D.3.9.4EV Substance CodeSUB194220
    D.3.10 Strength
    D.3.10.1Concentration unit µg microgram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number5
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNMENINGOCOCCAL GROUP W OLIGOSACCHARIDES CONJUGATED TO CORYNEBACTERIUM DIPHTHERIAE C7(ß197) M8 (CRM197) PROTEIN
    D.3.9.2Current sponsor codeN/A
    D.3.9.3Other descriptive nameMENINGOCOCCAL GROUP W OLIGOSACCHARIDES CONJUGATED TO CORYNEBACTERIUM DIPHTHERIAEC7 (ß197) M8 (CRM197) PROTEIN
    D.3.10 Strength
    D.3.10.1Concentration unit µg microgram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number5
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNMENINGOCOCCAL GROUP Y OLIGOSACCHARIDES CONJUGATED TO CORYNEBACTERIUM DIPHTHERIAE C7(Â197) M8 (CRM197) PROTEIN
    D.3.9.2Current sponsor codeN/A
    D.3.9.3Other descriptive nameMENINGOCOCCAL GROUP Y OLIGOSACCHARIDES CONJUGATED TO CORYNEBACTERIUM DIPHTHERIAEC7 (Â197) M8 (CRM197) PROTEIN
    D.3.9.4EV Substance CodeSUB77060
    D.3.10 Strength
    D.3.10.1Concentration unit µg microgram(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 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) 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.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/infusion
    D.8.4Route of administration of the placeboSubcutaneous use
    D.8 Placebo: 2
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboSolution for injection/infusion
    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 gravis generalizzata
    E.1.1.1Medical condition in easily understood language
    Generalized Myasthenia Gravis
    Miastenia gravis generalizzata
    E.1.1.2Therapeutic area Diseases [C] - Nervous System Diseases [C10]
    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 effect of pozelimab + cemdisiran on daily functioning
    that is impacted by signs and symptoms in patients with symptomatic
    generalized myasthenia gravis (gMG)
    L’obiettivo primario dello studio è valutare l’effetto di pozelimab + cemdisiran sulle funzioni quotidiane che risentono di segni e sintomi in pazienti con miastenia gravis generalizzata (generalized Myasthenia Gravis, [gMG]) sintomatica
    E.2.2Secondary objectives of the trial
    • To evaluate the effect of pozelimab + cemdisiran and cemdisiran
    monotherapy on:
    - Clinician-assessed signs of MG and muscle strength
    - Daily functioning that is impacted by signs and symptoms in patients
    with symptomatic gMG (cemdisiran monotherapy only)
    - Proportion of patients with improvements in daily function that is
    impacted by signs and symptoms of MG
    - Proportion of patients that have improvements in clinician-assessed
    signs of MG and muscle strength
    - Health related quality of life
    - Proportion of patients with minimal MG symptoms
    - Patient- and clinician-reported signs and symptoms of MG
    • To evaluate the safety and tolerability of pozelimab + cemdisiran
    combination and cemdisiran monotherapy
    • To assess the concentrations of total pozelimab in serum
    • To assess the concentrations of cemdisiran and its metabolites in
    plasma
    • To assess the immunogenicity of pozelimab and of cemdisiran
    • To study the effect on complement activation following treatment
    • Valutare l’effetto di pozelimab+cemdisiran e cemdisiran in monoterapia su:
    -Segni di miastenia gravis e forza muscolare valutati dal medico
    -Funzioni quotidiane che risentono di segni e sintomi in pazienti con gMG sintomatica(solo cemdisiran in monoterapia)
    -Percentuale di pazienti con miglioramenti delle funzioni quotidiane che risentono di segni e sintomi della MG
    -Percentuale di pazienti che presentano miglioramenti dei segni della MG e della forza muscolare valutati dal medico
    -Qualità della vita correlata allo stato di salute
    -Percentuale di pazienti con sintomi minimi di MG
    -Segni e sintomi di MG riferiti dal paziente e dal medico
    Valutare:
    • la sicurezza e la tollerabilità della combinazione pozelimab + cemdisiran e di cemdisiran in monoterapia
    • le concentrazioni totali di pozelimab nel siero
    • le concentrazioni di cemdisiran e dei suoi metaboliti nel plasma
    • l’immunogenicità di pozelimab e cemdisiran
    • Studiare l’effetto sull’attivazione del complemento dopo il trattamento
    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: Future Biomedical Research (Optional)
    Patients who agree to participate in the FBR sub-study will be required to consent to this optional sub-study before samples are banked for FBR.
    Additional samples will be collected for FBR. The samples may be utilized for FBR that may or may not be directly related to the study, including
    being used as reference samples and assay development or validation.

    Pharmacogenomic Analysis (Optional)
    Patients who agree to participate in the genomics sub-study will be required to consent to this optional sub-study before collection of the
    samples. DNA and RNA samples will be collected for pharmacogenomics analyses to understand the genetic determinants of efficacy and safety associated with the treatments in this study and the molecular basis of MG and related diseases.

    Altre tipologie di sottostudi
    specificare il titolo, la data e la versione di ogni sottostudio con i relativi obiettivi: Ricerca biomedica futura (facoltativa)
    Ai pazienti che acconsentono a partecipare al sottostudio di ricerca biomedica futura (Future Biomedical Research, [FBR]) sarà richiesto di acconsentire a questo sottostudio facoltativo prima che i campioni siano conservati per l’FBR. Saranno prelevati campioni aggiuntivi per l’FBR. I campioni possono essere utilizzati per una FBR che può essere o non essere direttamente correlata allo studio, incluso l’uso come campioni di riferimento e sviluppo o convalida del saggio.

    Analisi farmacogenomica (facoltativa)
    Ai pazienti che acconsentono a partecipare al sottostudio di genomica sarà richiesto di acconsentire a questo sottostudio facoltativo prima della raccolta dei campioni. Saranno raccolti campioni di DNA e RNA per le analisi di farmacogenomica per comprendere i determinanti genetici di efficacia e sicurezza associati ai trattamenti in questo studio e la base molecolare della MG e delle malattie correlate.
    E.3Principal inclusion criteria
    1. Male or female patients =18 years of age at screening (or = legal age
    of adulthood based on local regulations, whichever is older)
    2. Patient with documented diagnosis of myasthenia gravis (MG) based
    on medical history and supported by previous evaluations as described
    in the protocol
    3. Documented prior history of positive serologic test or a positive result
    during screening of anti-acetylcholine receptor (AChR) antibodies or
    anti-LRP4 antibodies.
    4. Myasthenia Gravis Foundation of America (MGFA) Clinical
    Classification Class II to IVa at screening
    5. Myasthenia Gravis-Activities of Daily Living (MG-ADL) score =6 at
    screening. Ocular items should not contribute more than 50% of MG-ADL
    total score
    6. Currently receiving an acetylcholinesterase inhibitor or documented
    reason for not using acetylcholinesterase inhibitor therapy per
    investigator
    7. Currently receiving an immunosuppressive therapy (IST) for MG, or
    documented reason why the patient is not taking an IST per investigator
    8. If currently receiving an IST, not anticipated to have IST dosage
    changed before randomization or during double-blind treatment period
    (DBTP).
    NOTE: Other Inclusion Criteria apply
    1. Pazienti di sesso maschile o femminile di età =18 anni allo screening (o = maggiore età legale in base alle normative locali, a seconda di quale sia l’età maggiore)
    2. Paziente con diagnosi di miastenia gravis (MG) documentata in base all’anamnesi medica e supportata da valutazioni precedenti come descritto nel protocollo
    3. Anamnesi pregressa documentata di test sierologico positivo o risultato positivo durante lo screening di anticorpi anti-recettore dell’acetilcolina (anti-Acetylcholine Receptor, [AChR]) o anticorpi anti-proteina 4 correlata al recettore della lipoproteina (anti-Lipoprotein Receptor-related Protein, 4, [anti-LRP4]).
    4. Classificazione clinica di classe da II a IV alla visita di screening secondo la Myasthenia Gravis Foundation of America (MGFA)
    5. Punteggio =6 delle attività della vita quotidiana con la miastenia gravis (Myasthenia Gravis-Activities of Daily Living, [MG-ADL]) allo screening. Gli elementi oculari non devono contribuire più del 50% al punteggio totale di MG-ADL
    6. Attuale trattamento con un inibitore dell’acetilcolinesterasi o motivo documentato per il mancato utilizzo della terapia con inibitore dell’acetilcolinesterasi secondo lo sperimentatore
    7. Attuale trattamento con una terapia immunosoppressiva (Immunosuppressive Therapy, [IST]) per la MG o motivo documentato per cui il paziente non sta assumendo un IST secondo lo sperimentatore
    8. Se sta attualmente ricevendo un IST, non si prevede di modificare il dosaggio dell’IST prima della randomizzazione o durante il periodo di trattamento in doppio cieco (Double-Blind Treatment Period, [DBTP]).
    NOTA: si applicano altri criteri di inclusione.
    E.4Principal exclusion criteria
    1. Patients with a positive serologic test for antibodies to muscle specific
    tyrosine kinase (MuSK) during screening
    2. History of thymectomy within 12 months prior to screening or planned
    during the study
    3. History of malignant thymoma (patients with stage 1 may be
    enrolled), or history of cancer within the past 5 years, except for
    adequately treated basal cell skin cancer, squamous cell skin cancer, or
    in situ cervical cancer
    4. Myasthenic crisis or Myasthenia Gravis Foundation of America (MGFA)
    Class V within 1 month of screening
    5. No documented meningococcal vaccination within 5 years prior to
    screening visit unless vaccination will be administered during the
    screening period and prior to initiation of study treatment
    6. Known contraindication to meningococcal vaccines (group ACWY
    conjugate and group B vaccines) as described in the protocol
    7. Patients who require antibiotics for meningococcal prophylaxis and
    have a contraindication, warning, or precaution precluding the use of
    penicillin class and penicillin-alternative antibiotics planned to be used
    for prophylaxis, or a history of intolerance leading to the discontinuation
    of these antibiotics
    8. Positive hepatitis B surface antigen or hepatitis C virus ribonucleic
    acid (RNA) during screening.
    9. History of HIV infection
    NOTE: Other Exclusion Criteria apply
    1. Pazienti con test sierologico positivo per anticorpi contro la tirosin chinasi muscolare specifica (Muscle Specific tyrosine Kinase, [MuSK]) durante lo screening
    2. Anamnesi di timectomia nei 12 mesi precedenti lo screening o prevista durante lo studio
    3. Anamnesi di timoma maligno (i pazienti allo stadio 1 possono essere arruolati) o anamnesi di tumore negli ultimi 5 anni, ad eccezione di tumore cutaneo basocellulare adeguatamente trattato, tumore cutaneo squamocellulare o tumore cervicale in situ
    4. Crisi miastenica o Classe V secondo la Myasthenia Gravis Foundation of America (MGFA) entro 1 mese dallo screening
    5. Nessuna vaccinazione meningococcica documentata nei 5 anni precedenti la visita di screening, a meno che la vaccinazione non sia stata somministrata durante il periodo di screening e prima dell’inizio del trattamento dello studio
    6. Controindicazione nota ai vaccini contro il meningococco (coniugato del gruppo ACWY e vaccini del gruppo B), come descritto nel protocollo
    7. Pazienti che necessitano di assumere antibiotici per la profilassi meningococcica e presentano una controindicazione, un’avvertenza o una precauzione che precluda l’uso degli antibiotici di classe penicillina e degli antibiotici alternativi alla penicillina che si prevede di utilizzare per la profilassi o un’anamnesi di intolleranza che porta all’interruzione di questi antibiotici
    8. Positività all’antigene di superficie dell’epatite B o all’acido ribonucleico (Ribonucleic Acid, [RNA]) del virus dell’epatite C durante lo screening.
    9. Anamnesi di infezione dal virus dell’immunodeficienza umana (Human Immunodeficiency Virus, [HIV])
    NOTA: si applicano altri criteri di esclusione.
    E.5 End points
    E.5.1Primary end point(s)
    Change in Myasthenia Gravis-Activities of Daily Living (MG-ADL) total
    score from baseline to week 24
    Variazione nel punteggio totale delle attività della vita quotidiana con la miastenia gravis (MG-ADL) dal basale alla settimana 24
    E.5.1.1Timepoint(s) of evaluation of this end point
    Baseline to Week 24
    Dal basale alla Settimana 24
    E.5.2Secondary end point(s)
    1. Change from baseline in Quantitative Myasthenia Gravis (QMG) score
    at week 24
    2. Proportion of patients responding on the MG-ADL, with a responder
    defined as one with a =3-point improvement from baseline to week 24
    3. Proportion of patients responding on the QMG, with a responder
    defined as one with a =5-point improvement from baseline to week 24
    4. Proportion of patients with consistent response on the MG-ADL,
    defined as patients with at least a 2-point MG-ADL improvement on 2 or
    more consecutive assessments spanning 4 or more weeks during the
    DBTP
    5. Proportion of patients with minimal symptom expression (MSE,
    defined by a score of 0 to 1 on the MG-ADL) at week 24
    6. Change from baseline in the Myasthenia Gravis Composite (MGC) total
    score at week 24
    7. Change from baseline in Myasthenia Gravis Quality of Life (MG
    QOL15r) total score at week 24
    8. Proportion of patients with improvement point thresholds of =2, 4, 5,
    6, 7, 8, 9, or 10 on MG-ADL at week 24
    9. Proportion of patients with improvement point thresholds of =3, 4, 6,
    7, 8, 9, or 10 on QMG at week 24
    10. Incidence and severity of treatment-related adverse events (TEAEs),
    serious adverse events (SAEs), and adverse events of special interest
    (AESIs) in patients treated with pozelimab + cemdisiran or placebo
    through week 24
    11. Concentrations of total pozelimab in serum at nominal time-points
    12. Concentrations of cemdisiran and its metabolites in plasma at
    nominal time points
    13. Incidence of treatment-emergent anti-drug antibodies (ADAs) to
    pozelimab after
    repeated doses over time
    14. Incidence of treatment-emergent ADAs to cemdisiran after repeated
    doses over time
    15. Change and percent change in CH50 over time
    1. Variazione rispetto al basale del punteggio quantitativo della miastenia gravis (Quantitative Myasthenia Gravis, QMG) alla Settimana 24
    2. Percentuale di pazienti che rispondono alla scala MG-ADL, laddove il responder deve riportare un miglioramento di =3 punti dal basale alla Settimana 24
    3. Percentuale di pazienti che rispondono alla scala QMG, laddove il responder deve riportare un miglioramento di =5 punti dal basale alla Settimana 24
    4. Percentuale di pazienti con risposta costante alla scala MG-ADL, ovvero con miglioramento di almeno 2 punti sulla scala MG-ADL in 2 o più valutazioni consecutive nell’arco di 4 o più settimane durante il DBTP
    5. Percentuale di pazienti con espressione minima dei sintomi (Minimal Symptom Expression, [MSE]) (ovvero con un punteggio da 0 a 1 sulla scala MG-ADL) alla Settimana 24
    6. Variazione rispetto al basale del punteggio totale composito della miastenia gravis (Myasthenia Gravis Composite, [MGC]) alla Settimana 24
    7. Variazione rispetto al basale del punteggio totale del questionario sulla qualità della vita nella miastenia gravis (Myasthenia Gravis Quality of Life, [MGQOL]15r) alla Settimana 24
    8. Percentuale di pazienti con soglie dei punti di miglioramento >2, 4, 5, 6, 7, 8, 9 o 10 sulla scala MG-ADL alla Settimana 24
    9. Percentuale di pazienti con soglie dei punti di miglioramento >3, 4, 6, 7, 8, 9 o 10 sulla scala QMG alla Settimana 24
    10. Incidenza e gravità di eventi avversi emergenti dal trattamento (Treatment-Emergent Adverse Event, [TEAE]), eventi avversi gravi (Serious Adverse Event, [SAE]) ed eventi avversi di particolare interesse (Adverse Event of Special Interest, [AESI]) in pazienti trattati con pozelimab + cemdisiran o placebo fino alla Settimana 24
    11. Concentrazioni totali di pozelimab nel siero in punti temporali nominali
    12. Concentrazioni di cemdisiran e dei suoi metaboliti nel plasma in punti temporali nominali
    13. Incidenza di anticorpi anti-farmaco (Antidrug Antibody, [ADA]) emergenti dal trattamento contro pozelimab in seguito a
    dosi ripetute nel tempo
    14. Incidenza di ADA emergenti dal trattamento diretti contro cemdisiran in seguito a dosi ripetute nel tempo
    15. Variazione e variazione percentuale di CH50 nel tempo
    E.5.2.1Timepoint(s) of evaluation of this end point
    1-10: Baseline to Week 24
    11-15: Though study duration, approximately 172 weeks
    1-10: Dal basale alla Settimana 24
    11-15: Per l’intera durata dello studio, circa 172 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 No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group 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 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 concerned4
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA34
    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
    Belgium
    Canada
    Czechia
    Denmark
    France
    Germany
    Italy
    Korea, Republic of
    Poland
    Russian Federation
    Spain
    Taiwan
    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
    The end of study is defined as the date the last patient completes the
    last study visit, withdraws from the study, or is lost to follow-up (ie,
    the study patient can no longer be contacted by the investigator).
    La fine dello studio è definita come la data in cui l’ultimo paziente completa l’ultima visita dello studio, si ritira dallo studio o risulta perso al follow-up (ovvero, lo sperimentatore non riesce più a contattarlo).
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years3
    E.8.9.1In the Member State concerned months3
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years4
    E.8.9.2In all countries concerned by the trial months6
    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: 200
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 10
    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 state8
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 126
    F.4.2.2In the whole clinical trial 210
    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
    Nessuno
    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 Decision2021-12-13
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2021-11-10
    P. End of Trial
    P.End of Trial StatusOngoing
    For support, visit the EMA Service Desk , log in using your EMA account and open a ticket specifying "EU CTR" in your request.
    If you do not have an account, please visit the EMA Account management page page click on "Create an EMA account" and follow the instructions.
    The status of studies in GB is no longer updated from 1.1.2021
    For the UK, as from 1.1.2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2022 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA