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    Summary
    EudraCT Number:2014-003865-11
    Sponsor's Protocol Code Number:NEOD001-CL002
    National Competent Authority:Italy - Italian Medicines Agency
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2021-01-20
    Trial results View results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedItaly - Italian Medicines Agency
    A.2EudraCT number2014-003865-11
    A.3Full title of the trial
    A Phase 3, Randomized, Multicenter, Double-Blind, Placebo-Controlled, 2-
    Arm, Efficacy and Safety Study of NEOD001 Plus Standard of Care vs.
    Placebo Plus Standard of Care in Subjects with Light Chain (AL)
    Amyloidosis
    Studio di fase 3,multicentrico, randomizzato, in doppio cieco, controllato con placebo, a due bracci teso a valutare l’efficacia e la sicurezza di NEOD001 più terapia standard rispetto a placebo più terapia standard in pazienti affetti da amiloidosi da catene leggere (AL)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A study to see how effective and safe NEO001 is when given together with
    the standard treatment in comparison to placebo together with the
    standard treatment in people with Light Chain (AL) Amyloidosis.
    Uno Studio teso a valutare l'efficacia e la sicurezza del NEOD001 somministrato insieme alla terapia standard in pazienti effetti da amiloidosi da catene leggere (AL)
    A.3.2Name or abbreviated title of the trial where available
    A study to see how effective and safe NEO001 is when given together with the standard treatment in c
    Uno Studio teso a valutare l'efficacia e la sicurezza del NEOD001 somministrato insieme alla terapia
    A.4.1Sponsor's protocol code numberNEOD001-CL002
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT02312206
    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 SponsorPROTHENA THERAPEUTICS LIMITED
    B.1.3.4CountryIreland
    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 supportProthena Therapeutics Limited
    B.4.2CountryIreland
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationProthena Biosciences Inc
    B.5.2Functional name of contact pointJay Soto
    B.5.3 Address:
    B.5.3.1Street Address331 Oyster Point Blvd
    B.5.3.2Town/ citySouth San Francisco, California
    B.5.3.3Post code94080
    B.5.3.4CountryUnited States
    B.5.4Telephone number001650 615 2131
    B.5.5Fax number001
    B.5.6E-mailJay.soto@prothena.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 Yes
    D.2.5.1Orphan drug designation numberEU/3/13/1100
    D.3 Description of the IMP
    D.3.1Product nameNEOD001
    D.3.2Product code NEOD001
    D.3.4Pharmaceutical form Powder for solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.9.2Current sponsor codeNEOD001
    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 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.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 infusion
    D.8.4Route of administration of the placeboIntravenous use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Light chain (AL) amyloidosis involves a hematologic disorder caused by
    clonal plasma cells that produce misfolded immunoglobulin light chains.
    Overproduction of misfolded light chains results in both soluble,
    aggregated forms of light chains and insoluble,fibrillar deposits of
    abnormal AL protein (amyloid),in the tissues and organs. This can cause
    a range of symptoms and organ dysfunction including cardiac,renal,and
    hepatic dysfunction,gastrointestinal involvement and neuropathy and
    macroglossia
    L'amidoilosi a catene leggere (AL) è un disordine di origine ematologica causato da cellule del sangue clonate che producono immunoglobulina a catene leggere mal ripiegata. La sovraproduzione delle catene leggere mal ripiegate porta alla formazione sia di forme aggregate solubili sia di depositi fibrillari insolubili di prioteine anormali AL (amiloidi) nei tessuti e negli organi. Questo può causare una serie di sintomi e disfunsione di organi, incluso disfunsione cardiaca, renale, epatica, coinv
    E.1.1.1Medical condition in easily understood language
    Light chain (AL) amyloidosis is a blood disorder, which causes
    progressive organ damage as a result of the misfolding of proteins. This
    disease can produce a range of symptoms and organ dysfuction
    L'Amiloidosi a catene leggere (AL) è un malattia del sangue che causa un progressivo danneggiamento degli organi come risultato di un ripiegamento scorretto delle proteine. Questa malattia può produrr
    E.1.1.2Therapeutic area Diseases [C] - Blood and lymphatic diseases [C15]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level PT
    E.1.2Classification code 10036673
    E.1.2Term Primary amyloidosis
    E.1.2System Organ Class 10021428 - Immune 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 efficacy of NEOD001 plus standard of care vs. placebo plus standard of care when administered intravenously in subjects with AL amyloidosis by assessing time to all- cause mortality or cardiac
    hospitalization
    Valutare l'efficacia di NEOD001 più terapia standard rispetto a placebo più terapia standard quando somministrato per via endovenosa in pazienti con amiloidosi AL esaminando il tempo al decesso per qualsiasi causa o al ricovero per problemi cardiaci.
    E.2.2Secondary objectives of the trial
    In subjects with AL amyloidosis, comparing NEOD001 plus standard of care vs. placebo plus standard of care:
    • To evaluate the safety of NEOD001
    • To evaluate the cardiac response rate as assessed by NT-proBNP
    • To evaluate health-related quality of life using the Short Form 36 questionnaire (SF-36)
    • To evaluate cardiac functional response using the 6 Minute Walk Test (6MWT)
    • To evaluate the renal response rate using established criteria
    • To evaluate peripheral neuropathy using the Neuropathy Impairment Scale – Lower Limbs (NIS-LL)
    • To evaluate the hepatic response rate according to consensus criteria
    • To evaluate cardiac-specific quality of life using the Kansas City Cardiomyopathy Questionnaire (KCCQ)
    • To evaluate time to cardiac mortality or cardiac hospitalization
    • To evaluate time to all-cause mortality
    Nei pazienti con amiloidosi AL, tramite il confronto di NEOD001 più terapia standard rispetto a placebo più terapia standard:
    • Valutare la sicurezza di NEOD001
    • Valutare il tasso di risposta cardiaca sulla base del frammento NT-proBNP

    • Valutare la qualità di vita correlata allo stato di salute generale mediante il questionario breve Short Form-36 (SF-36)
    • Valutare la risposta della funzionalità cardiaca utilizzando il test del cammino in 6 minuti (6MWT)
    • Valutare il tasso di risposta renale utilizzando criteri stabiliti
    • Valutare la neuropatia periferica utilizzando la scala Neuropathy Impairment Scale – Lower Limbs (NIS-LL)
    • Valutare il tasso di risposta epatica utilizzando i criteri di consenso
    • Valutare la qualità di vita correlata alla funzionalità cardiaca mediante il questionario KCCQ (Kansas City Cardiomyopathy Questionnaire)
    • Valutare il tempo al decesso per cause cardiache o al ricovero per problemi cardiaci
    • Valutare il tempo al decesso per qualsiasi causa
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Subjects must meet all of the following criteria:
    1. Aged = 18 years
    2. Newly diagnosed and AL amyloidosis treatment naïve
    3. Bone marrow demonstrating clonal plasma cells
    4. Confirmed diagnosis of AL amyloidosis by the following:
    • Histochemical diagnosis of amyloidosis determined by polarizing light microscopy of green birefringent material in Congo red-stained tissue
    specimens OR characteristic electron microscopy appearance AND
    • Confirmatory immunohistochemistry OR mass spectroscopy of AL amyloidosis
    5. Confirmed diagnosis of AL amyloidosis by mass spectrometry or immunoelectron microscopy of amyloid material in tissue biopsy if the subject meets any of the following:
    • is black or African American
    • is over 75 years of age with concurrent monoclonal gammopathy
    • has a history of familial amyloidosis and has concurrent monoclonal gammopathy
    OR
    • If the subject meets any of the above 3 conditions and has echocardiographic evidence of amyloidosis, biopsy-proven amyloidosis with a monoclonal gammopathy and no tissue is available for mass spectrometry or immunoelectron microscopy, the subject must have gene sequencing consistent with transthyretin (TTR) wild type (e.g., no TTR mutation present) AND must score 0 in technetium-99m-3,3- diphosphono-1,2 propanodicarboxylic acid (99mTc-DPD; Rapezzi 2011), hydroxymethylenediphosphonate (99mTc-HMDP; Galat 2015), or pyrophosphate (99mTc-PYP; Bokhari 2013) scintigraphy
    6. Cardiac involvement as defined by all of the following:
    • Past documented or presently noted clinical signs and symptoms supportive of a diagnosis of heart failure in the setting of a confirmed diagnosis of AL amyloidosis in the absence of an alternative explanation for heart failure
    • Either an endomyocardial biopsy demonstrating AL amyloidosis or an echocardiogram demonstrating a mean left ventricular wall thickness at diastole > 12 mm in the absence of other causes (e.g., severe hypertension, aortic stenosis), which would adequately explain the degree of wall thickening
    • NT-proBNP = 650 pg/mL and = 8500 pg/mL
    7. Planned first-line chemotherapy contains bortezomib administered weekly and SC
    8. Adequate bone marrow reserve, hepatic function, and renal function, as demonstrated by:
    • absolute neutrophil count (ANC) = 1.0 x10^9/L
    • platelet count = 75 x 10^9/L
    • hemoglobin = 9 g/dL
    • total bilirubin = 2 times the upper limit of normal (x ULN)
    • aspartate aminotransferase (AST) / serum glutamic oxaloacetic transaminase (SGOT) = 3 x ULN
    • alanine aminotransferase (ALT) / serum glutamic pyruvic transaminase (SGPT) = 3 x ULN
    • alkaline phosphatase (ALP) = 5 x ULN (except for subjects with hepatomegaly and isozymes specific to liver, rather than bone)
    • estimated glomerular filtration rate (eGFR) = 30 mL/min/1.73 m^2 as estimated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation
    9. Seated systolic blood pressure (BP) 90-180 mmHg
    10. Distance walked during each Screening 6MWT is =30 meters and = 550 meters
    11. Women of childbearing potential (WOCBP) must have two negative

    pregnancy tests during Screening, the second within 24 hours prior to the first administration of study drug and must agree to use highly effective physician-approved contraception from Screening to 90 days following the last study drug administration
    12. Male subjects must be surgically sterile or must agree to use highly effective physician-approved contraception from Screening to 90 days following the last study drug administration
    13. Ability to understand and willingness to sign an informed consent form prior to initiation of any study procedures
    Criteri di inclusione (i pazienti devono soddisfare tutti i seguenti criteri):
    1. 1. Età pari o superiore a 18 anni
    2. Diagnosi recente di amiloidosi AL naïve al trattamento
    3. Midollo osseo che evidenzia la presenza di plasmacellule clonali
    4. Diagnosi confermata di amiloidosi AL in base a quanto segue:
    • Diagnosi istochimica di amiloidosi determinata mediante microscopia a luce polarizzata di materiale birifrangente verde in campioni di tessuto colorati con rosso Congo OPPURE aspetto caratteristico al microscopio elettronico
    E
    • Immunoistochimica OPPURE spettroscopia di massa che conferma l'amiloidosi AL
    5. Diagnosi confermata di amiloidosi AL mediante spettrometria di massa o microscopia immunoelettronica di materiale amiloide nella biopsia del tessuto, se il paziente soddisfa una qualsiasi delle seguenti condizioni:
    • È nero o afro-americano
    • È di età superiore a 75 anni con concomitante gammopatia monoclonale
    • Ha precedenti di amiloidosi familiare e concomitante gammopatia monoclonale
    OPPURE
    • Se soddisfa una qualsiasi delle 3 condizioni sopra e presenta evidenza ecocardiografica di amiloidosi, amiloidosi provata mediante biopsia con una gammopatia monoclonale e non è disponibile tessuto per la spettrometria di massa o la microscopia immunoelettronica, il paziente deve presentare un sequenziamento dei geni coerente con transtiretina (TTR) "wild type" (ad es., nessuna mutazione della TTR presente) E un punteggio 0 nella scintigrafia al tecnezio-99m-3,3-difosfono-1,2 acido propanodicarbossilico (99mTc DPD; Rapezzi 2011), idrossimetilenedifosfonato (99mTc HMDP; Galat 2015) o pirofosfato (99mTc PYP; Bokhari 2013)
    6. Interessamento cardiaco definito da tutti i seguenti:
    • Segni e sintomi clinici documentati in passato o osservati attualmente a sostegno di una diagnosi di insufficienza cardiaca nel contesto di una diagnosi confermata di amiloidosi AL, in assenza di una spiegazione alternativa per l'insufficienza cardiaca
    • Biopsia endomiocardica che dimostra amiloidosi AL o ecocardiogramma che dimostra uno spessore medio della parete ventricolare sinistra alla diastole > 12 mm in assenza di altre cause (ad es., ipertensione grave, stenosi aortica), che giustificherebbe adeguatamente il grado di ispessimento della parete
    • NT-proBNP = 650 pg/ml e = 8.500 pg/ml
    7. La chemioterapia di prima linea pianificata contiene bortezomib somministrato settimanalmente e per via sottocutanea (SC)
    8. Riserva midollare e funzionalità epatica e renale adeguate come attestato da:
    • Conta assoluta dei neutrofili (ANC) = 1,0 x109/l
    • Conta piastrinica = 75 × 109/l
    • Emoglobina = 9 g/dl
    • Bilirubina totale =2 volte il limite superiore di normalità (ULN)
    • Aspartato aminotransferasi (AST)/transaminasi glutammico-ossalacetica nel siero (SGOT) = 3 x ULN
    • Alanina aminotransferasi (AST)/transaminasi glutammico-piruvica nel siero (SGPT) = 3 x ULN
    • Fosfatasi alcalina (ALP) = 5 x ULN (eccetto per pazienti con epatomegalia e isoenzimi specifici del fegato, anziché delle ossa)
    • Velocità di filtrazione glomerulare stimata (eGFR) = 30 ml/min/1,73 m2 in base alle stime ottenute dall'equazione Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)
    9. Pressione arteriosa sistolica in posizione seduta 90-180 mmHg
    10. Distanza percorsa durante ciascun test 6MWT allo screening > 30 metri e < 550 metri
    11. Le pazienti in grado di procreare (WOCBP) devono presentare due test di gravidanza negativi durante lo screening, il secondo nelle 24 ore precedenti la prima somministrazione del farmaco dello studio e devono accettare di utilizzare un metodo contraccettivo altamente efficace, approvato dal medico (Appendice 4) dallo screening fino a 90 giorni dopo l'ultima somministrazione del farmaco dello studio
    12. I pazienti di sesso maschile devono essere chirurgicamente sterili o accettare di utilizzare un metodo contraccettivo altamente efficace, approvato dal medico (Appendice 4) dallo screening fino a 90 giorni dopo l'ultima somministrazione del farmaco dello studio
    13. Capacità di comprendere e disponibilità a firmare un modulo di consenso informato prima di avviare qualsiasi procedura dello studio
    E.4Principal exclusion criteria
    Subjects must meet none of the following criteria:
    1. Non-AL amyloidosis
    2. NT-proBNP < 650 pg/mL or > 8,500 pg/mL
    3. Meets the International Myeloma Working Group (IMWG) definition of Multiple Myeloma (see Appendix 5)
    *Note that subjects who meet the IMWG definition of symptomatic multiple myeloma with signs and/or symptoms attributable only to associated amyloidosis and who do not otherwise meet the criteria for diagnosis of smoldering myeloma are potentially eligible upon approval of the Sponsor.
    4. Subject is eligible for and plans to undergo ASCT or organ transplant
    5. Symptomatic orthostatic hypotension that in the medical judgment of the Investigator would interfere with subject's ability to safely receive treatment or complete study assessments
    6. Myocardial infarction, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or ECG evidence of acute ischemia, within 6 months prior to the Month 1-Day 1 Visit
    7. Severe valvular stenosis (e.g. aortic or mitral stenosis with a valve area <1.0 cm2) or severe congenital heart disease
    8. ECG evidence of acute ischemia or active conduction system abnormalities with the exception of any of the following:
    • First degree AV-block
    • Second degree AV-block Type 1 (Mobitz Type 1 / Wenckebach type)
    • Right or left bundle branch block
    • Atrial fibrillation with a controlled ventricular rate (uncontrolled [i.e.,
    >110 bpm] ventricular rate is not allowed [determined by an average of three beats in Lead II or three representative beats if Lead II is not representative of the overall ECG])
    9. Peripheral neuropathy assessed as National Cancer Institute-Common Terminology Criteria for Adverse Events ( NCI-CTCAE) Grade 2 with pain, Grade 3 or Grade 4
    10. Subject is receiving oral or IV antibiotics, antifungals or antivirals within 1 week of Month 1-Day 1 with the exception of prophylactic oral agents
    11. Prior treatment with hematopoietic growth factors, transfusions of blood or blood products within 1 week of Month 1-Day 1
    12. Prior radiotherapy within 4 weeks of Month 1-Day 1
    13. Major surgery within 4 weeks of Month 1-Day 1 or planned major surgery during the study
    14. Active malignancy with the exception of any of the following:
    • Adequately treated basal cell carcinoma, squamous cell carcinoma, or in situ cervical cancer
    • Adequately treated Stage I cancer from which the subject is currently in remission and has been in remission for 2 years
    • Low-risk prostate cancer with Gleason score < 7 and prostate-specific antigen < 10 mg/mL
    • Any other cancer from which the subject has been disease-free for = 2 years

    15. History of severe allergy to any of the components of NEOD001 such as histidine/L histidine hydrochloride monohydrate, trehalose
    dehydrate, or polysorbate 20 or history of Grade = 3 infusion-related AEs or hypersensitivity to another monoclonal antibody, or known hypersensitivity to diphenhydramine (or an equivalent H1 antihistamine) or acetaminophen (or its equivalent, paracetamol)
    16. Known or history of uncontrolled, active human immunodeficiency virus (HIV), Hepatitis B or Hepatitis C infection
    17. Prior treatment with plasma cell-directed chemotherapy, NEOD001, 11-1F4, anti-serum amyloid P antibody, doxycycline for amyloid, or other investigational treatment directed at amyloid
    18. Treatment with another investigational agent within 30 days of Month 1-Day 1
    19. Women who are pregnant or lactating
    20. Any condition which could interfere with, or the treatment for which might interfere with, the conduct of the study or which would, in the opinion of the Investigator, unacceptably increase the subject's risk by participating in the study
    21. Subject is under legal custodianship
    22. History of epilepsy or seizure disorder with the exception of childhood febrile seizures
    23. Waldenström's macroglobulinemia and/or immunoglobulin M (IgM) monoclonal gammopathy
    Criteri di esclusione (i pazienti non devono soddisfare nessuno dei seguenti criteri):
    1. 1. Amiloidosi non-AL
    2. NT-proBNP < 650 pg/ml o > 8.500 pg/ml
    3. Soddisfa la definizione di mieloma multiplo dell'International Myeloma Working Group (IMWG) (Appendice 5)
    *Si noti che i pazienti che rispondono alla definizione IMWG di mieloma multiplo sintomatico con segni e/o sintomi attribuibili solo ad amiloidosi associata sono potenzialmente idonei previa approvazione dello Sponsor.
    4. Paziente idoneo e che preveda di sottoporsi ad ASCT o trapianto di organo
    5. Ipotensione ortostatica sintomatica che secondo il giudizio medico dello sperimentatore potrebbero interferire con la capacità del paziente di sottoporsi in modo sicuro al trattamento o completare gli esami dello studio
    6. Infarto miocardico, angina non controllata, gravi aritmie ventricolari non controllate o evidenza elettrocardiografica (ECG) di ischemia acuta nei 6 mesi precedenti la visita del giorno 1 del mese 1
    7. Grave stenosi valvolare (ad es., stenosi aortica o mitralica con superficie valvolare <1,0 cm2) o grave malattia cardiaca congenita
    8. Evidenza elettrocardiografica di ischemia acuta o anomalie attive del sistema di conduzione, ad eccezione di una qualsiasi delle seguenti condizioni:
    • Blocco AV di primo grado
    • Blocco AV di secondo grado Tipo 1 (Mobitz Tipo 1 / Tipo Wenckebach)
    • Blocco di branca destra o sinistra
    • Fibrillazione atriale con frequenza ventricolare controllata [non è consentita la frequenza ventricolare non controllata (cioè > 110 bpm) determinata da una media di tre battiti nella derivazione II o tre battiti rappresentativi se la derivazione II non è rappresentativa dell'EKG complessivo])
    9. Neuropatia periferica di grado 2 con dolore, grado 3 o grado 4 secondo i criteri comuni di terminologia per gli eventi indesiderati del National Cancer Institute (NCI-CTCAE)
    10. Utilizzo di antibiotici, antifungini o antivirali per via orale o EV entro 1 settimana dal giorno 1 del mese 1, ad eccezione degli agenti profilattici orali
    11. Precedente trattamento con fattori della crescita emopoietici, trasfusioni di sangue o emoderivati entro 1 settimana dal giorno 1 del mese 1
    12. Precedente radioterapia entro 4 settimane dal giorno 1 del mese 1
    13. Intervento chirurgico maggiore entro 4 settimane dal giorno 1 del mese 1 o programmato nel corso dello studio
    14. Neoplasia attiva ad eccezione di una qualsiasi delle seguenti condizioni:
    • Carcinoma basocellulare, carcinoma squamocellulare o cancro cervicale in situ adeguatamente trattato
    • Cancro allo stadio I adeguatamente trattato da cui il paziente è attualmente in fase di remissione e lo è da 2 anni
    • Cancro della prostata a basso rischio con punteggio di Gleason < 7 e antigene prostatico specifico < 10 mg/ml
    • Qualsiasi altro cancro da cui il paziente è libero da = 2 anni
    15. Anamnesi di allergia grave a uno qualsiasi dei componenti di NEOD001, quali istidina/L-istidina cloridrato monoidrato, trealosio diidrato o polisorbato 20, anamnesi di eventi avversi di grado = 3 correlati all'infusione, ipersensibilità a un altro anticorpo monoclonale o ipersensibilità nota alla difenidramina (o a un antistaminico H1 equivalente) o all'acetaminofene (o a un suo equivalente, paracetamolo)
    16. Infezione attiva nota, o precedente, da HIV, epatite B o epatite C non controllata
    17. Precedente trattamento con chemioterapia diretta alle plasmacellule, NEOD001, 11-1F4, anticorpo anti-amiloide P del siero, doxiciclina per amiloide o altro trattamento sperimentale diretta contro l'amiloide
    18. Trattamento con un altro agente sperimentale entro 30 giorni dal giorno 1 del mese 1
    19. Pazienti in gravidanza o che allattano al seno
    20. Qualsiasi condizione in grado di interferire con la conduzione dello studio, o con il trattamento per il quale lo studio viene condotto, o che, a giudizio dello sperimentatore, potrebbe comportare un aumento inaccettabile del rischio per il paziente qualora partecipasse allo studio
    21. Pazienti sotto custodia legale
    22. Anamnesi di epilessia o crisi convulsive ad eccezione delle convulsioni febbrili durante l'infanzia
    23. Macroglobulinemia di Waldenström e/o gammopatia monoclonale delle immunoglobuline M (IgM)
    E.5 End points
    E.5.1Primary end point(s)
    Time to all-cause mortality or cardiac hospitalization
    Tempo al decesso per qualsiasi causa o al ricovero per problemi cardiaci
    E.5.1.1Timepoint(s) of evaluation of this end point
    As adjudicated by the CEC
    Secondo il giudizio del CEC
    E.5.2Secondary end point(s)
    NT-proBNP best response from baseline to Month 9
    • Change from baseline to Month 9 in the Physical Component Score of the SF-36
    • Change from baseline to Month 9 in the 6MWT
    • For renal-evaluable subjects, renal best response from baseline to Month 9
    • For subjects with peripheral neuropathy due to AL amyloidosis, change from baseline to Month 9 in the NIS-LL score
    • For hepatic-evaluable subjects, hepatic best response from baseline to Month 9
    • Change from baseline to Month 9 in the KCCQ
    • Time to cardiac mortality or cardiac hospitalization as adjudicated by the CEC
    • Time to all-cause mortality
    • Migliore risposta dell'NT-proBNP dal basale al mese 9
    • Variazione dal basale al mese 9 nel punteggio della componente fisica dell'SF-36
    • Variazione dal basale al mese 9 nel 6MWT
    • Per i pazienti valutabili sotto il profilo renale, migliore risposta renale dal basale al mese 9 (Appendice 1)
    • Per i pazienti con neuropatia periferica a causa di amiloidosi AL, variazione dal basale al mese 9 nel punteggio NIS LL (Appendice 1)
    • Per i pazienti valutabili sotto il profilo epatico, migliore risposta epatica dal basale al mese 9 (Appendice 1)
    • Variazione dal basale al mese 9 nel KCCQ
    • Tempo al decesso per cause cardiache o al ricovero per problemi cardiaci secondo il giudizio del CEC
    • Tempo al decesso per qualsiasi causa
    E.5.2.1Timepoint(s) of evaluation of this end point
    NT-proBNP best response from baseline to Month 9
    • Change from baseline to Month 9 in the SF-36
    • Change from baseline to Month 9 in the 6MWT
    • Renal best response from baseline to Month 9 (Palladini 2014)
    • Change from baseline to Month 9 in the NIS-LL score
    • Hepatic best response from baseline to Month 9 (Comenzo 2012)
    • Change from baseline to Month 9 in the KCCQ
    • Time to cardiac mortality or cardiac hospitalization as adjudicated by the CEC
    • Time to all-cause mortality
    • Migliore risposta dell'NT-proBNP dal basale al mese 9
    • Variazione dal basale al mese 9 nell'SF-36
    • Variazione dal basale al mese 9 nel 6MWT
    • Migliore risposta renale dal basale al mese 9 (Appendice 1)
    • Variazione dal basale al mese 9 nel punteggio NIS LL (Appendice 1)
    • Migliore risposta epatica dal basale al mese 9 (Appendice 1)
    • Variazione dal basale al mese 9 nel KCCQ
    • Tempo al decesso per cause cardiache o al ricovero per problemi cardiaci secondo il giudizio del CEC
    • Tempo al decesso per qualsiasi causa
    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 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 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 concerned4
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA37
    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
    Canada
    Israel
    United States
    Austria
    Belgium
    Czechia
    Denmark
    France
    Germany
    Greece
    Italy
    Netherlands
    Spain
    United Kingdom
    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 study will end when approximately 156 primary endpoint events
    have occurred and EOS visits have been completed for all subjects who
    remain on study at that time. Events are defined as deaths due to any
    cause, or cardiac hospitalizations as adjudicated by the CEC
    Lo Studio terminerà approssimativamente quando si saranno manifestati circa 156 eventi di endpoint primario e le visite di fine studio saranno state completate per tutti i pazienti che si trovano nello studio in quel momento. Gli eventi sono definiti da morte per qualunque causa oppure ricovero ospedaliero per problemi cardiache, secondo giudizio del CEC
    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 months6
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years3
    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: 36
    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 state20
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 100
    F.4.2.2In the whole clinical trial 236
    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)
    At the time of study completion (i.e., once approximately 156 primary endpoint events have been reached), subjects still on treatment will be invited to enrol in an open-label extension study of NEOD001.
    Al termine dello Studio (es. una volta che sono stati raggiunti approssimativamente 156 eventi di endpoint primario), i pazienti che sono ancora in trattamento saranno invitati ad arruolarsi nello studio di estensione in aperto di NEOD001.
    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 Decision2015-07-15
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2015-05-11
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2018-06-08
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