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 were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

  • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43801   clinical trials with a EudraCT protocol, of which   7263   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 on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
    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

    EudraCT Number:2015-000359-26
    Sponsor's Protocol Code Number:ESTEVE-SANF-201
    National Competent Authority:Spain - AEMPS
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2016-02-03
    Trial results
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedSpain - AEMPS
    A.2EudraCT number2015-000359-26
    A.3Full title of the trial
    Phase I/II safety, tolerability and initial efficacy study of adeno-associated viral vector serotype 9 containing human sulfamidase gene after intracerebroventricular administration to patients with MPSIIIA.
    Estudio de fase I/II para evaluar la seguridad, tolerabilidad y eficacia inicial del vector viral adenoasociado de serotipo 9 conteniendo el gen de la sulfamidasa humana tras su administración por vía intracerebroventricular a pacientes con MPSIIIA.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    First study in patients to assess safety, tolerability and inittial efficacy of the new gene therapy product to treat MPSIIIA.
    Primer estudio en pacientes para evaluar la seguridad, tolerabilidad y eficacia inicial del nuevo producto de terapia génica para tratar MPSIIIA.
    A.4.1Sponsor's protocol code numberESTEVE-SANF-201
    A.7Trial is part of a Paediatric Investigation Plan Yes
    A.8EMA Decision number of Paediatric Investigation PlanP/149/2014
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorLaboratorios del Dr. Esteve, S.A.
    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 supportLaboratorios del Dr. Esteve,S.A.
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationLaboratorios del Dr. Esteve,S.A.
    B.5.2Functional name of contact pointAdelaida Morte
    B.5.3 Address:
    B.5.3.1Street AddressAv. Mare de Déu de Montserrat,221
    B.5.3.2Town/ cityBarcelona
    B.5.3.3Post code08041
    B.5.4Telephone number349344660006581
    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/3/11/877
    D.3 Description of the IMP
    D.3.1Product nameVector viral adenoasociado de serotipo 9 que contiene el gen de la sulfamidasa humana
    D.3.2Product code AAV9-CAG-coh-SGSH
    D.3.4Pharmaceutical form Suspension for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOther use (Noncurrent)
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNVector viral adenoasociado de serotipo 9 que contiene el gen de la sulfamidasa humana
    D.3.9.1CAS number 1352588-20-5
    D.3.9.2Current sponsor codeAAV9- CAG-coh-SGSH
    D.3.9.3Other descriptive nameVector viral adenoasociado de serotipo 9 que contiene el gen de la sulfamidasa humana
    D.3.9.4EV Substance CodeSUB178857
    D.3.10 Strength
    D.3.10.1Concentration unit Other
    D.3.10.2Concentration typerange
    D.3.10.3Concentration number1000000000000 to 1000000000000000
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) Yes
    D. cell therapy medicinal product No
    D. therapy medical product Yes
    D. Engineered Product No
    D. ATIMP (i.e. one involving a medical device) No
    D. 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
    Mucopolysaccharidosis type IIIA (Sanfilippo A syndrome) is an inherited lysosomal storage disease caused by a specific lysosomal enzyme deficiency that leads to intracellular accumulation of the GAG heparan sulphate (HS). It is caused by a deficiency of one of the four enzymes involved in the lysosomal degradation of HS. In the case of subtype A is the heparan N-sulfatase (SGSH).
    La Mucopolisacaridosis tipo IIIA (síndrome de Sanfilippo A) es una enfermedad hereditaria de almacenamiento lisosomal causada por una deficiencia de la enzima lisosomal específica que conduce a la acumulación intracelular del Heparán Sulfato GAG (HS). Es causada por una deficiencia de una de las cuatro enzimas implicadas en la degradación lisosomal de HS. En el caso del subtipo A es el heparán N-sulfatasa (SGSH).
    E.1.1.1Medical condition in easily understood language
    Inherited disease caused by the deficiency of Sulfamidase, the enzime that degrades Heparan Sulfate, leading to its accumulation in the cells causing the severe signs and symptoms of MPSIIIA
    Enfermedad hereditaria causada por la deficiencia de Sulfamidasa, enzima que degrada el Heparan Sulfato,conduciendo a su acumulación en las células causando los graves signos y síntomas de la MPS IIIA
    E.1.1.2Therapeutic area Diseases [C] - Nutritional and Metabolic Diseases [C18]
    MedDRA Classification
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    The main objective of this study is to determine the safety and tolerability, including the immune response, after Intracerebroventricular administration of a single dose of AAV9-CAG-coh-SGSH in two dosage cohorts of patients with MPSIIIA.
    El objetivo principal del estudio es determinar la seguridad y tolerabilidad, incluyendo la respuesta inmunológica, tras la administración por vía intracerebroventricular de una dosis de AAV9-CAG-coh-SGSH a dos cohortes de pacientes con MPSIIIA.
    E.2.2Secondary objectives of the trial
    To assess the pharmacodynamic profile and the initial efficacy after Intracerebroventricular administration of a single dose of AAV9-CAG-coh-SGSH in two dosage cohorts of patients with MPSIIIA to estimate the dose required to significantly ameliorate the phenotype.
    To evaluate the correlation between the pharmacodynamic assessments and the clinical evolution, in order to establish the optimal biomarker to assess the evolution / amelioration of the disease.
    To collect data regarding potential tests that can be evaluation criteria for the subsequent pivotal study.
    To assess viral shedding.
    Evaluar el perfil farmacodinámico y la eficacia inicial tras la administración por vía intracerebroventricular de una dosis única de AAV9-CAG-coh-SGSH a dos cohortes de pacientes con MPSIIIA para estimar la dosis requerida que mejorará significativamente el
    Evaluar la correlación entre la evaluación farmacodinámica y la evolución clínica de los pacientes para establecer el biomarcador óptimo que permita evaluar la evolución / mejora de la enfermedad.
    Recoger datos relativos a las pruebas que potencialmente puedan constituir criterios de evaluación a ser incluidos en el subsiguiente estudio confirmatorio.
    Evaluar la diseminación viral.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1.- Male and female patients aged 2 years or older.
    2.- Patients with confirmed MPSIIIA (by genotype), with underlying missense mutation at least in one of the alleles for the disease and documented deficiency in sulfamidase enzyme activity of less than or equal to 10%.
    3.- Onset of clinical manifestations related to MPSIIIA during the first 6 years of life.
    4.- Patients with an adaptive behaviour score between 40 and 90 as evaluated by the Vineland Adaptive Behaviour Scale (Vineland-II).
    5.- Patients not dependent on a wheelchair.
    6.- Patients without severe sensory deficit (blindness, deafness that requires headset).
    7.- Patients with stable symptomatic treatment (depending on weight) within the last 3 months, with no anticipated changes in medication regimen.
    8.- Patients with no contraindication for surgical procedure and/or anaesthesia. Patients taking non-steroidal anti-inflammatory drugs (NSAIDs) should discontinue their use.
    9.- Patients medically stable to accommodate the protocol requirements, including travelling and assessments.
    10.- Signed informed consent.
    1.- Pacientes de ambos sexos de 2 o más años de edad.
    2.- Pacientes con diagnóstico confirmado de MPSIIIA (por el genotipo), con mutación missense en, al menos, uno de los alelos y una deficiencia documentada en la actividad enzimática
    sulfamidasa (menor o igual al 10% del valor normal de actividad).
    3.- Inicio de las manifestaciones clínicas de la enfermedad durante los primeros 6 años de vida.
    4.- Pacientes con una puntuación entre 40 y 90 en la Escala Adaptativa Vineland (Vineland-II).
    5.- Pacientes que no precisen silla de ruedas.
    6.- Pacientes que no presenten déficits sensoriales severos (ceguera, sordera que requiera audífono).
    7.- Pacientes con tratamiento sintomático estable (en función del peso) en los últimos 3 meses, sin cambios previstos en este régimen de medicación.
    8.- Pacientes que no presenten contraindicaciones al procedimiento quirúrgico y/o a la anestesia. Los pacientes que estén tomando antinflamatorios no esteroideos (AINEs) deberán discontinuar su uso.
    9.- Pacientes estables medicamente que puedan acomodarse a los requisitos del protocolo, incluyendo los viajes y las evaluaciones.
    10.- Firma del consentimiento informado.
    E.4Principal exclusion criteria
    1.- Patient deterioration that may compromise the interpretation of the study results.
    2.- Patients with neutralising antibodies (NAb) against AAV9 in cerebrospinal fluid.
    3.- Epilepsy resistant to treatment.
    4.- Patients with significant co-morbid conditions.
    5.- Any contraindication for anaesthesia and product administration procedure, including major risk factors for haemorrhage.
    6.- Any vaccination 30 days before investigational product administration.
    7.- Patients who have received any medication with the objective of modifying the natural course of the disease, i.e. gene transfer agents or enzyme replacement therapy.
    1.- Deterioro del paciente que pueda comprometer la interpretación de los resultados del estudio.
    2.- Pacientes con anticuerpos neutralizantes (NAc) frente al AAV9 en el líquido cefalorraquídeo.
    3.- Epilepsia resistente al tratamiento.
    4.- Pacientes con comorbilidades significativas.
    5.- Cualquier contraindicación a la anestesia y al procedimiento quirúrgico para la administración del producto, incluyendo factores de riesgo de hemorragia.
    6.- Administración de cualquier vacuna en los 30 días previos a la administración del producto en investigación.
    7.- Pacientes que hayan recibido cualquier medicación con el objetivo de modificar el curso natural de la enfermedad, como otros productos de terapia génica o terapias de reemplazo enzimático.
    E.5 End points
    E.5.1Primary end point(s)
    Safety and Tolerability:
    All safety and tolerability parameters will be evaluated at regular time points after AAV9-CAG-coh-SGSH product administration and will be assessed by comparison to screening / baseline evaluations.
    - Physical examination.
    - Adverse events.
    - Blood laboratory tests (haematology and chemistry) and Urinalysis.
    - Inflammatory response assessment in blood.
    - Immune response: interferon gamma ELISPOT, intracellular cytokine staining and lymphocyte proliferation in peripheral blood mononuclear cells and neutralizing antibodies (NAb) to the AAV9 vector and antibodies to the transgene quantified in CSF and serum.
    - ECG.
    - Vital signs.
    - Imaging Assessments: Magnetic Resonance Imaging with Spectroscopy (MRI-S) and brain volume, Hepatic Ultrasonography assessing volume and structure.

    Pharmacodynamic - Efficacy:
    All pharmacodynamic and efficacy parameters will be evaluated at regular time points after AAV9-CAG-coh-SGSH product administration and will be assessed by comparison to screening / baseline evaluations.
    A first estimate of efficacy will be based on the clinical endpoints at 12 months after product administration.
    - Sulfamidase enzymatic activity quantified in cerebrospinal fluid (CSF) and blood (leukocytes and plasma).
    - Heparan Sulfate (HS) levels quantified in CSF, plasma, and urine.
    - Neurological and physical examination.
    - Neurobehavioural skills assessed by the Vineland Adaptive Behaviour Scale (Vineland-II).
    - Cognitive, language, social-emotional, motor and adaptive development assessed by the Bayley Scales of Infant Development.
    - The specific recently developed Sanfilippo Behaviour Rating Scale.
    - Evaluation of quality of life by the PedsQL scale.
    - Sleep assessment by Polysomnography and the Sleep Disturbance Scale for Children (SDSC).
    - Brain Auditory Evoked Potentials(BAEP).
    - Real-time ultrasound elastography of the Achilles tendon.
    Seguridad y Tolerabilidad:
    Todos los parámetros de seguridad se evaluarán a diferentes tiempos tras la administración de AAV9-CAG-coh-SGSH y se valorarán en comparación a las evaluaciones basales.
    • Exploración física.
    • Acontecimientos adversos.
    • Tests de laboratorio en sangre (hematología y bioquímica) y urianálisis.
    • Evaluación de la respuesta inflamatoria en sangre.
    • Respuesta Immune (interferon gamma ELISPOT, intracellular cytokine staining y proliferación de linfocitos en mononucleares de sangre periférica y anticuerpos frente el vector AAV9 y frente al transgen cuantificados en líquido cefalorraquídeo (LCR) y suero.
    • ECG.
    • Constantes vitales.
    • Pruebas de imagen: Resonancia magnética con espectroscopía (RMN-S) y volumen cerebral y Ecografía hepática con evaluación de volumen y estructura.
    Farmacodinamia y Eficacia:
    Todos los parámetros farmacodinámicos y de eficacia se evaluarán a diferentes tiempos tras la administración de AAV9-CAG-coh-SGSH y se valorarán en comparación a las evaluaciones basales. Se realizará una primera estimación de la eficacia basada en las valoraciones clínicas realizadas a los 12 meses tras la administración del producto.
    • Actividad enzimática sulfamidasa cuantificada en LCR y sangre (leucocitos y plasma).
    • Niveles de Heparán Sulfato (HS) cuantificados en LCR, plasma y orina.
    • Examen neurológico y físico.
    • Evaluación neuroconductual mediante con la Escala Adaptativa Vineland (Vineland-II).
    • Desarrollo cognitivo, del lenguaje, socio-emocional, motor y adaptativo evaluado por medio de la Escala de Desarrollo Infantil de Bayley.
    • Escala específica Sanfilippo Behaviour Rating Scale, recientemente desarrollada.
    • Evaluación de la calidad de vida mediante la escala PedsQL.
    • Evaluación del sueño mediante registros de polisomnografía y mediante la escala Sleep Disturbance Scale for Children.
    • Potenciales Evocados Auditivos Cerebrales (PEAC).
    • Elastografía en tiempo real del tendón de Aquiles.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Neuro/Physical exam: screening (SC), D -1, D1-discharge (DC), week (W) 2 ,4, month (M) 2,2.5, 3, 6, 9, 12, 18, year (Y) 2-5; AEs: SC, D-1, D0, D1- DC, W2,4, M 2, 2.5, 3, 6, 9, 12, 18,Y 2-5; Laboratory tests/ ECG: SC, D-1, DC, W4,M 3, 6, 9, 12, 18, Y2-5; Inflammatory resp: SC, D -1, DC, W4, M 3, 6, 9, 12,18; Humoral Immune resp: SC, D -1, D0, W4, M 3, 6,9, 12, 18, Y 2-5; T-Cell Immune resp: SC, W2 ,4, M 3, 6, 12, Y 3; Vital signs: SC, D -1, D1-DC ,W4, M 3, 6, 9, 12, 18, Y2-5; MRI-S: SC, D2, M12; Hepatic Ultrasonography: SC, W4, M 3, 6, 9, 12, 18, Y 2-5; Sulfamidase activity/ HS levels: SC, W4, M 3, 6, 9 12, 18,Y 2-5; Neuropsychological scales: SC, M 3, 6, 12, 18, Y 2-5; PedsQL: SC, M 6, 12, 18,Y 2-5; Polysomnography, BAEP, elastography: SC, M12,Y2-5; SDSC: SC, W4, M 3, 6, 9, 12, 18,Y 2-5.
    Examen físico y neurolófico: selección (SC), D -1, D1-alta (AL), semana (S) 2 ,4, mes (M) 2,2.5, 3, 6, 9, 12, 18, año (A) 2-5; AAs: SC, D-1, D0, D1- DC, S2,4, M 2, 2.5, 3, 6, 9, 12, 18,A2-5; tests laboratorio/ ECG: SC, D-1, AL, S4,M 3, 6, 9, 12, 18, A2-5; resp. inflamatoria: SC, D -1, AL, S4, M 3, 6, 9, 12,18; resp. humoral: SC, D -1, D0, S4, M 3, 6,9, 12, 18, A2-5; resp. inmune célular: SC, S2 ,4, M 3, 6, 12, Y 3; Signos Vitales: SC, D -1, D1-DC ,S4, M 3, 6, 9, 12, 18, A2-5; RNM: SC, D2, M12; Ultrasonografía hepática: SC, S4, M 3, 6, 9, 12, 18, A2-5; Actividad Sulfamidasa/Niveles HS : SC, S4, M 3, 6, 9 12, 18,A 2-5; escalas neuropsicológicas: SC, M 3, 6, 12, 18, A 2-5; PedsQL: SC, M 6, 12, 18,A2-5; Polisomnografía, PEAC, elastografía: SC, M12,A2-5; SDSC: SC, W4, M 3, 6, 9, 12, 18,A2-5.
    E.5.2Secondary end point(s)
    Not applicable
    No aplica
    E.5.2.1Timepoint(s) of evaluation of this end point
    Not applicable
    No aplica
    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 Yes
    E.6.8Bioequivalence No
    E.6.9Dose response Yes
    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) Yes
    E.7.1.1First administration to humans Yes
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E. trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled No
    E.8.1.1Randomised No
    E.8.1.2Open Yes
    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.8.3 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.8.5The trial involves multiple Member States No
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA No
    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
    Last patient last visit
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years5
    E.8.9.1In the Member State concerned months
    E.8.9.1In the Member State concerned days
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 Yes
    F.1.1Number of subjects for this age range: 6
    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) Yes
    F. of subjects for this age range: 3
    F.1.1.6Adolescents (12-17 years) Yes
    F. 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. of subjects incapable of giving consent
    Mentally handicaped children and/or adolescents
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state6
    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)
    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 Decision2016-04-29
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2015-10-15
    P. End of Trial
    P.End of Trial StatusOngoing
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands