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    Summary
    EudraCT Number:2020-005995-37
    Sponsor's Protocol Code Number:COAV101A12306
    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:2021-08-17
    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 number2020-005995-37
    A.3Full title of the trial
    A Phase IIIb, open-label, single-arm, single-dose, multicenter study to evaluate the safety, tolerability and efficacy of gene replacement therapy with intravenous OAV101 (AVXS-101) in pediatric patients with spinal muscular atrophy (SMA)
    Studio di fase IIIB, in aperto, a braccio singolo, a dose singola, multicentrico per valutare la sicurezza, tollerabilità ed efficacia della terapia di sostituzione genica con OAV 101 (AVXS-101) per via endovenosa in pazienti pediatrici con atrofia muscolare spinale (SMA)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Safety and Efficacy of Intravenous OAV101 (AVXS-101) in Pediatric Patients With Spinal Muscular Atrophy (SMA)
    Sicurezza ed efficacia di OAV101 (AVXS-101) in pazienti pediatrici con atrofia muscolare spinale (Spinal Muscular Atrophy – SMA)
    A.3.2Name or abbreviated title of the trial where available
    SMART
    SMART
    A.4.1Sponsor's protocol code numberCOAV101A12306
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT04851873
    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 SponsorNOVARTIS PHARMA AG
    B.1.3.4CountrySwitzerland
    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 supportNovartis Pharma AG
    B.4.2CountrySwitzerland
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationNovartis Pharma AG
    B.5.2Functional name of contact pointClinical Trial Information Desk
    B.5.3 Address:
    B.5.3.1Street AddressForum 1, Novartis Campus
    B.5.3.2Town/ cityBasel
    B.5.3.3Post code4056
    B.5.3.4CountrySwitzerland
    B.5.4Telephone number0041613241111
    B.5.5Fax number0041613248001
    B.5.6E-mailclinicaltrial.enquiries@novartis.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 Prednisolone
    D.2.1.1.2Name of the Marketing Authorisation holderBruno Farmaceutici
    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 namePrednisolone
    D.3.2Product code [-]
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNPREDNISOLONE
    D.3.9.1CAS number 50-24-8
    D.3.9.2Current sponsor code-
    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: 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 Prednisolone
    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 namePrednisolone
    D.3.2Product code [-]
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNPREDNISOLONE
    D.3.9.1CAS number 50-24-8
    D.3.9.2Current sponsor code-
    D.3.10 Strength
    D.3.10.1Concentration unit µg microgram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number2500
    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.2.1.1.2Name of the Marketing Authorisation holderBruno Farmaceutici
    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 namePrednisolone
    D.3.2Product code [-]
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNPREDNISOLONE
    D.3.9.1CAS number 50-24-8
    D.3.9.2Current sponsor code-
    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.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.2.1.1.2Name of the Marketing Authorisation holderBruno Farmaceutici
    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 namePrednisolone
    D.3.2Product code [-]
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNPREDNISOLONE
    D.3.9.1CAS number 50-24-8
    D.3.9.2Current sponsor code-
    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: 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 No
    D.2.1.1.1Trade name Zolgensma
    D.2.1.1.2Name of the Marketing Authorisation holderNovartis Gene Therapies EU Limited - EU/1/20/1443/001-037
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community Yes
    D.2.5.1Orphan drug designation numberEMA/OD/028/15
    D.3 Description of the IMP
    D.3.1Product nameOAV101
    D.3.2Product code [AVXS-101]
    D.3.4Pharmaceutical form Solution for infusion
    D.3.4.1Specific paediatric formulation Yes
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNONASEMNOGENE ABEPARVOVEC
    D.3.9.1CAS number 1922968-73-7
    D.3.9.2Current sponsor codeOAV101
    D.3.9.3Other descriptive namePreviously termed sc.AAV9.CB.SMN and AVXS-101
    D.3.9.4EV Substance CodeSUB193254
    D.3.10 Strength
    D.3.10.1Concentration unit Other
    D.3.10.2Concentration typenot less then
    D.3.10.3Concentration number200000000
    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) Yes
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product Yes
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Spinal Muscular Atrophy
    Atrofia muscolare spinale
    E.1.1.1Medical condition in easily understood language
    Spinal Muscular Atrophy
    Atrofia muscolare spinale
    E.1.1.2Therapeutic area Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.1
    E.1.2Level PT
    E.1.2Classification code 10041582
    E.1.2Term Spinal muscular atrophy
    E.1.2System Organ Class 10010331 - Congenital, familial and genetic 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 assess the safety and tolerability of IV OAV101 over a 12-month period in participants with SMA weighing = 8.5 kg and = 21 kg
    Valutare la sicurezza e la tollerabilità di OAV101 IV in un periodo di tempo di 12 mesi in partecipanti affetti da SMA e con peso corporeo = 8.5 kg e = 21 kg.
    E.2.2Secondary objectives of the trial
    To determine the efficacy of IV OAV101 at 6 and 12 months post dose in participants with SMA weighing = 8.5 kg and = 21 kg as measured by change from baseline in:
    • Developmental motor milestone achievement as assessed by World Health Organization-Multicentre Growth Reference Study (WHO-MGRS) and Bayley Scales of Infant and Toddler Development-Third Edition (Bayley-III) criteria
    • Hammersmith Functional Motor Scale - Expanded (HFMSE)
    • Revised Upper Limb Module (RULM), as appropriate according to participant age
    Determinare l’efficacia di OAV101 IV a 6 e 12 mesi post-dose in partecipanti affetti da SMA e con peso corporeo = 8.5 kg e = 21 kg misurata tramite la variazione rispetto al basale dei seguenti:
    • Raggiungimento dei traguardi motori di sviluppo in base ai criteri World Health Organization-Multicentre Growth Reference Study (WHO-MGRS) e Bayley Scales of Infant and Toddler Development-Third Edition (Bayley-III) (fare riferimento alla Tabella 2-1 del Protocollo per i dettagli)
    • Hammersmith Functional Motor Scale - Expanded (HFMSE)
    • Revised Upper Limb Module (RULM), in base a quanto appropriato a seconda dell’età del partecipante.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Written informed consent/assent obtained prior to any assessment performed
    2. Symptomatic SMA diagnosis based on gene mutation analysis with bi-allelic SMN1 mutations (deletion or point mutations) and any copy of SMN2 gene.
    3. Weight = 8.5 kg and = 21 kg at the time of Screening Visit 2
    4. Naive to treatment or have discontinued an approved drug/therapy
    5. Up-to date on recommended childhood vaccinations and RSV prophylaxis with palivizumab (also known as Synagis), per local standard of care
    1. Consenso/assenso informato scritto ottenuto prima dell’effettuazione di qualsiasi valutazione
    2. Diagnosi di SMA sintomatica basata sull’analisi della mutazione genica con mutazioni bialleliche di SMN1 (delezione o mutuazione puntiforme) e qualsiasi copia del gene SMN2.
    3. Peso corporeo = 8.5 kg e = 21 kg, al momento delle Visita di screening 2
    4. Partecipanti naïve al trattamento o che hanno interrotto un farmaco approvato/una terapia approvata
    5. Partecipanti in regola con le vaccinazioni infantili raccomandate e la profilassi per virus respiratorio sinciziale (Respiratory Syncytial Virus – RSV) con palivizumab (noto anche come Synagis), in base allo standard di cura locale
    E.4Principal exclusion criteria
    Participants meeting any of the following criteria are not eligible for inclusion in this study.
    1. Previous OAV101 use or previous use of any AAV9 gene therapy
    2. BMI < 3rd percentile based on WHO Child Growth Standard
    3. Participant with history of aspiration pneumonia or signs of aspiration (eg, coughing or sputtering of food) within 4 weeks prior to screening
    4. Anti-AAV9 antibody titer > 1:50 as determined by ligand binding immunoassay at the time of screening
    5. History of gene therapy, hematopoietic transplantation, or solid organ transplantation
    6. Inability to take corticosteroids
    7. Concomitant use of immunosuppressive therapy, plasmapheresis, immunomodulators such as adalimumab, or immunosuppressive therapy within 3 months prior to gene replacement therapy (eg, cyclosporine, tacrolimus, methotrexate, rituximab cyclophosphamide, IV immunoglobulin)
    8. Requiring invasive ventilation, tracheostomy or awake non-invasive ventilation (standard of care nocturnal BiPAP is not considered exclusionary)
    9. Administration of vaccines 2 weeks prior to infusion of OAV101
    10. Awake hypoxemia (O2 saturation <95%) or awake oxygen saturation level decrease between screening and dosing that is clinically significant, as per investigator judgment.
    11. Clinically significant neurologic or neuromuscular conditions other than SMA as determined by the principal Investigator
    12. Clinically significant abnormalities in laboratory test results at Screening as determined by the Investigator
    13. Hepatic dysfunction (i.e. AST, ALT, bilirubin, GGT or GLDH, = ULN; CTCAE = 1) at Screening (with the exception of isolated AST elevation: in the absence of other liver laboratory abnormalities, isolated AST elevation is not considered exclusionary)
    14. Excluding SMA, any medically unstable condition considered clinically significant by the Investigator, including cardiomyopathy, hepatic dysfunction, kidney disorder, endocrine disorder, GI disorders, metabolic disorders, severe respiratory compromise and significant brain abnormalities at either Screening or Baseline that, in the opinion of the investigator, would interfere with the overall interpretation of safety or efficacy of the study
    15. Presence of a confirmed or suspected active infectious process from screening and up to dose administration
    16. If previously treated with disease modifying therapy, participants are excluded if they received
    - less than 3 doses of nusinersen (Spinraza®)
    - nusinersen (Spinraza®) within 4 months prior to Screening
    - risdiplam (EvrysdiTM) within 15 days prior to Screening (washout period of at least 5 half-lives before Screening)
    17. Use of other investigational drugs within 5 half-lives of enrollment/initiation of study treatment (select as appropriate) within 30 days (eg, small molecules) / or until the expected pharmacodynamic effect has returned to baseline (eg, biologics), whichever is longer; or longer if required by local regulations.
    18. History of hypersensitivity to any of the study treatments or its excipients or to drugs of similar chemical classes.
    19. Documented any parental consanguinity
    I partecipanti che soddisfano uno qualsiasi dei seguenti criteri non sono eleggibili per l’inclusione in questo studio.
    1. Pregresso utilizzo di OAV101 o pregresso utilizzo di qualsiasi terapia genica AAV9
    2. Indice di massa corporea (Body Mass Index – BMI) < 3° percentile in base allo standard WHO Child Growth
    3. Partecipanti con anamnesi di polmonite da aspirazione o segni di aspirazione (ad es. tosse o emissione di cibo) nelle 4 settimane precedenti lo screening
    4. Titolo anticorpale anti-AAV9 > 1:50 determinato da saggio immunologico del legame del ligando al momento dello screening
    5. Anamnesi di terapia genica, trapianto ematopoietico o trapianto di organo solido
    6. Impossibilità di assumere corticosteroidi
    7. Utilizzo concomitante di terapia immunosoppressiva, plasmaferesi, immunomodulatori quali adalimumab, o terapia immunosoppressiva nei 3 mesi precedenti la terapia di sostituzione genica (ad es. ciclosporina, tacrolimus, metotrexato, rituximab, ciclofosfamide, immunoglobuline IV)
    8. Partecipanti che richiedono ventilazione invasiva, tracheostomia, o ventilazione non-invasiva in stato di veglia [le cure standard con BiPAP (Bi-Level Positive Airway Pressure) notturna non sono considerate motivo di esclusione]
    9. Somministrazione di vaccini 2 settimane prima l’infusione di OAV101
    10. Ipossiemia in stato di veglia (saturazione di ossigeno < 95%) o diminuzione del livello di saturazione di ossigeno in stato di veglia tra lo screening e la somministrazione che sia clinicamente significativa a giudizio dello sperimentatore
    11. Condizioni neurologiche o neuromuscolari clinicamente significative diverse dalla SMA come determinato dallo Sperimentatore Principale
    12. Anormalità nei risultati dei test di laboratorio clinicamente significative allo screening come determinato dallo Sperimentatore
    13. Disfunzione epatica (ovvero AST, ALT, bilirubina, GGT o GLDH = ULN; CTCAE = 1) allo screening (ad eccezione di aumenti isolati di ALT: in assenza di altre anormalità di laboratorio relative agli esami epatici, gli aumenti isolati di AST non sono considerati motivo di esclusione)
    14. Escludendo la SMA, qualsiasi condizione instabile da un punto di vista medico considerata clinicamente significativa dallo Sperimentatore, compresa cardiomiopatia, disfunzione epatica, disordini renali, disordini endocrini, disordini gastrointestinali, disordini metabolici, compromissione respiratoria severa e anormalità cerebrali significative allo screening o al basale che, a giudizio dello Sperimentatore, interferirebbero con l’interpretazione complessiva della sicurezza o dell’efficacia dello studio
    15. Presenza di un processo infettivo attivo confermato o sospetto dallo screening fino alla somministrazione della dose
    16. Se precedentemente trattati con una terapia che modifica la malattia, i partecipanti sono esclusi se hanno
    hanno ricevuto
    - meno di 3 dosi di nusinersen (Spinraza®)
    - nusinersen (Spinraza®) nei 4 mesi precedenti lo screening
    - risdiplam (EvrysdiTM) nei 15 giorni precedenti lo screening (periodo di washout di almeno 5 emivite prima dello screening)
    17. Utilizzo di altri farmaci sperimentali entro 5 emivite dal momento dell’arruolamento/inizio del trattamento in studio (selezionare in base a quanto appropriato) entro 30 giorni (ad esempio piccole molecole)/o fino a che l’effetto farmacodinamico atteso è ritornato al basale (ad esempio biologici), a seconda di quale dei due periodi sia più lungo; o più a lungo se richiesto dalle normative locali
    18. Anamnesi di ipersensibilità ad uno qualsiasi dei trattamenti in studio o ai relativi eccipienti o a farmaci di classi chimiche simili
    19. Qualsiasi consanguineità genitoriale documentata
    E.5 End points
    E.5.1Primary end point(s)
    1. Number of participants with treatment emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) An AE is any untoward medical occurrence (e.g. any unfavorable and unintended sign [including abnormal laboratory findings], symptom or disease) in a clinical investigation participant after providing written informed consent for participation in the study.
    2. Number of participants with important identified and important potential risks (Adverse Events of Special Interest (AESI)) The following are important identified and important potential risks (AESI) associated with OAV101: Hepatotoxicity, Thrombocytopenia, Cardiac adverse events, Sensory abnormalities suggestive of ganglionopathy, and Thrombotic microangiopathy. These will be assessed by the investigator.
    3. Change from baseline in vital signs measurements - systolic and diastolic blood pressure (mmHg)
    4. Change from baseline in vital signs measurements - respiratory rate (breaths per minute)
    5. Change from baseline in vital signs measurements - pulse (beats per minute)
    6. Change from baseline in vital signs measurements - temperature (degrees Celsius)
    7. Change from baseline in vital signs measurements - oxygen saturation level (%)
    1. Numero di partecipanti con eventi avversi (AE) emergenti dal trattamento ed eventi avversi gravi (SAE) Un AE è qualsiasi evento medico negativo (ad esempio qualsiasi segno sfavorevole e indesiderato [compresi i risultati di laboratorio anormali], sintomo o malattia) in un partecipante all'indagine clinica dopo aver fornito il consenso informato scritto per la partecipazione allo studio.
    2. Numero di partecipanti con importanti rischi identificati e importanti rischi potenziali (Adverse Events of Special Interest (AESI)) I seguenti sono importanti rischi identificati e importanti rischi potenziali (AESI) associati a OAV101: epatotossicità, trombocitopenia, eventi avversi cardiaci, anomalie sensoriali suggestive di ganglionopatia e microangiopatia trombotica. Questi saranno valutati dallo sperimentatore.
    3. Cambiamento rispetto al basale nelle misurazioni dei segni vitali - pressione sanguigna sistolica e diastolica (mmHg)
    4. Cambiamento rispetto al basale nelle misurazioni dei segni vitali - frequenza respiratoria (respiri al minuto)
    5. Cambiamento rispetto al basale nelle misurazioni dei segni vitali - polso (battiti al minuto)
    6. Cambiamento rispetto al basale nelle misurazioni dei segni vitali - temperatura (gradi Celsius)
    7. Cambiamento rispetto al basale nelle misurazioni dei segni vitali - livello di saturazione dell'ossigeno (%)
    E.5.1.1Timepoint(s) of evaluation of this end point
    12 months
    12 mesi
    E.5.2Secondary end point(s)
    1. Achievement of development motor milestones according to the BayleyScale of Infant and Toddler Development. Developmental motor milestones are assessed via the developmental milestone checklist, formed of 10 yes/no questions with optional video documentation. The developmental milestones are: head control, sitting with support, sitting without support, sitting without support for 30 seconds, hands-and-knees crawling, pulls to stand, standing with
    assistance, walking with assistance, standing alone and walking alone. A yes response indicates that the patient reached a particular development milestone.
    2. Change from baseline in Hammersmith Functional Motor Scale - Expanded (HFMSE), as appropriate according to participant age The HFMSE was devised for use in children with SMA to give objective
    information on motor ability and clinical progression. The HFMSE is formed of 33 assessments rated from 0 (unable to perform functional task) to 2 (able to perform functional task unassisted). Higher scores indicated higher levels of motor ability.
    3. Change from baseline in Revised Upper Limb Module (RULM), as appropriate according to participant age.
    The RULM assesses motor performance in the upper limbs from childhood through adulthood in ambulatory and non-ambulatory individuals with SMA. 'The scale consists of an entry item to establish functional levels and 19 items covering distal to proximal movements. The entry item is a modified version of the Brooke scale, including activities ranging from no functional use of hands (score 0) to full bilateral shoulder abduction (score 6). The entry item does not contribute to the total score but serves as a functional classification of overall upper limb functional ability. Of the remaining 19 items, 18 are scored on a 3 point scoring system and 1 item is scored on a 2 point scoring system. The test is performed unilaterally using the limb preferred by the participant. The total score ranges from 0, if all the items cannot be performed, to 37, if all the activities are achieved fully without any compensation. ' Higher scores indicate higher levels of motor ability.
    1. Raggiungimento delle tappe motorie dello sviluppo secondo la BayleyScale of Infant and Toddler Development. Le pietre miliari dello sviluppo motorio sono valutate tramite la lista di controllo delle pietre miliari dello sviluppo, formata da 10 domande sì/no con documentazione video opzionale. Le pietre miliari dello sviluppo sono: controllo della testa, seduto con supporto, seduto senza supporto, seduto senza supporto per 30 secondi, gattonamento con mani e ginocchia, tira per stare in piedi, in piedi con
    assistenza, camminare con assistenza, stare in piedi da solo e camminare da solo. Una risposta affermativa indica che il paziente ha raggiunto una particolare pietra miliare dello sviluppo.
    2. Cambiamento dal basale nella Hammersmith Functional Motor Scale - Expanded (HFMSE), a seconda dell'età del partecipante. La HFMSE è stata ideata per l'uso in bambini con SMA per fornire informazioni informazioni oggettive sulla capacità motoria e sulla progressione clinica. L'HFMSE è formato da 33 valutazioni valutate da 0 (incapace di eseguire compiti funzionali) a 2 (capace di eseguire compiti funzionali senza assistenza). Punteggi più alti indicano livelli più alti di abilità motoria.
    3. Cambiamento dal basale nel modulo Revised Upper Limb Module (RULM), a seconda dell'età del partecipante.
    Il RULM valuta le prestazioni motorie negli arti superiori dall'infanzia all'età adulta in soggetti SMA deambulanti e non deambulanti. La scala consiste in un item di ingresso per stabilire i livelli funzionali e 19 item che coprono i movimenti da distali a prossimali. L'item di ingresso è una versione modificata della scala Brooke, che include attività che vanno da nessun uso funzionale delle mani (punteggio 0) alla completa abduzione bilaterale della spalla (punteggio 6). L'item di ingresso non contribuisce al punteggio totale, ma serve come classificazione funzionale della capacità funzionale generale dell'arto superiore. Dei 19 elementi rimanenti, 18 sono valutati con un sistema di punteggio a 3 punti e 1 elemento è valutato con un sistema di punteggio a 2 punti. Il test viene eseguito unilateralmente utilizzando l'arto preferito dal partecipante. Il punteggio totale varia da 0, se tutte le voci non possono essere eseguite, a 37, se tutte le attività sono realizzate pienamente senza alcuna compensazione. Punteggi più alti indicano livelli più alti di abilità motoria.
    E.5.2.1Timepoint(s) of evaluation of this end point
    12 months
    12 mesi
    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 No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic Yes
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others Yes
    E.6.13.1Other scope of the trial description
    Tolerability
    Tollerabilità
    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 No
    E.8.1.1Randomised No
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    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 No
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial1
    E.8.3 The trial involves single site in the Member State concerned Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    E.8.4.1Number of sites anticipated in Member State concerned1
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA8
    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
    Taiwan
    United States
    Belgium
    France
    Germany
    Italy
    Portugal
    Spain
    Switzerland
    United Kingdom
    E.8.7Trial has a data monitoring committee No
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    Study completion is defined as when the last participant finishes their Study Completion visit and any repeat assessments associated with this visit have been documented and followed-up appropriately by the Investigator or, in the event of an early study termination decision, the date of that decision.
    Il completamento dello studio è definito come il momento in cui l'ultimo partecipante finisce la visita di completamento dello studio e tutte le valutazioni ripetute associate a questa visita siano state documentate e seguite in modo appropriato dallo dallo sperimentatore o, nel caso di una decisione di terminazione anticipata dello studio, la data di tale decisione.
    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 months11
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years1
    E.8.9.2In all countries concerned by the trial months11
    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 Yes
    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) Yes
    F.1.1.4.1Number of subjects for this age range: 17
    F.1.1.5Children (2-11years) Yes
    F.1.1.5.1Number of subjects for this age range: 10
    F.1.1.6Adolescents (12-17 years) Yes
    F.1.1.6.1Number of subjects for this age range: 3
    F.1.2Adults (18-64 years) No
    F.1.3Elderly (>=65 years) No
    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 No
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally Yes
    F.3.3.6.1Details of subjects incapable of giving consent
    infants, toddlers, children and adolescents
    -
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state2
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 14
    F.4.2.2In the whole clinical trial 30
    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)
    NA
    NA
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2021-09-28
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2021-06-17
    P. End of Trial
    P.End of Trial StatusCompleted
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