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    Summary
    EudraCT Number:2022-000079-38
    Sponsor's Protocol Code Number:DB-OTO-001
    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:2022-10-28
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedSpain - AEMPS
    A.2EudraCT number2022-000079-38
    A.3Full title of the trial
    A Phase 1/2, Open-Label, Multicenter Trial With a Single Ascending Dose Cohort With Unilateral Intracochlear Injection Followed by a Bilateral Injection Expansion Cohort to Evaluate the Safety, Tolerability, and Efficacy of DB-OTO in Children and Infants With Biallelic hOTOF Mutations
    Ensayo en fase I/II, abierto y multicéntrico con una cohorte de dosis ascendente única con inyección intracoclear unilateral seguida de una cohorte de ampliación con inyección bilateral para evaluar la seguridad, tolerabilidad y eficacia de db-oto en niños y lactantes con mutaciones bialélicas de hOTOF
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A trial to find the optimal dose of DB-OTO in infants and children with hearing loss
    Un ensayo para determinar la dosis óptima de DB-OTO en bebés y niños con pérdida auditiva
    A.4.1Sponsor's protocol code numberDB-OTO-001
    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 SponsorDecibel Therapeutics
    B.1.3.4CountryUnited States
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportDecibel Therapeutics Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationDecibel Therapeutics Inc.
    B.5.2Functional name of contact pointClinical Information
    B.5.3 Address:
    B.5.3.1Street Address1325 Boylston Street, Suite 500
    B.5.3.2Town/ cityBoston
    B.5.3.3Post code02215
    B.5.3.4CountryUnited States
    B.5.4Telephone number+1617-370-8701
    B.5.6E-mailclinical@decibeltx.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameDB-OTO
    D.3.2Product code DB-OTO
    D.3.4Pharmaceutical form Suspension for injection
    D.3.4.1Specific paediatric formulation Yes
    D.3.7Routes of administration for this IMPInjection (Noncurrent)
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNNA
    D.3.9.1CAS number NA
    D.3.9.2Current sponsor codeDB-OTO
    D.3.9.3Other descriptive nameDB-OTO-5
    D.3.9.4EV Substance CodeSUB295350
    D.3.10 Strength
    D.3.10.1Concentration unit Vector genome
    D.3.10.2Concentration typerange
    D.3.10.3Concentration number7200000000000 to 17500000000000
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNNA
    D.3.9.1CAS number NA
    D.3.9.2Current sponsor codeDB-OTO
    D.3.9.3Other descriptive nameDB-OTO-3
    D.3.9.4EV Substance CodeSUB295351
    D.3.10 Strength
    D.3.10.1Concentration unit Vector genome
    D.3.10.2Concentration typerange
    D.3.10.3Concentration number7200000000000 to 17500000000000
    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.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
    Congenital auditory neuropathy secondary to biallelic mutations of the otoferlin gene (hOTOF)
    Neuropatía auditiva congénita secundaria a mutaciones bialélicas del gen otoferlin (hOTOF)
    E.1.1.1Medical condition in easily understood language
    Infants and children who have hearing loss due to changes in the otoferlin gene. Patients with this diagnosis may be born with profound hearing loss and are not expected to improve without treatment.
    Lactantes y niños con pérdida de audición debido a cambios en el gen otoferlin.Los pacientes con este diagnóstico pueden nacer con pérdida auditiva profunda y no se espera que mejoren sin tratamiento.
    E.1.1.2Therapeutic area Body processes [G] - Genetic Phenomena [G05]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10011874
    E.1.2Term Deaf
    E.1.2System Organ Class 100000004854
    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 safety and tolerability of DB-OTO in young children and infants diagnosed with biallelic otoferlin gene (hOTOF) mutations
    •Evaluar la seguridad y tolerabilidad de DB-OTO en niños pequeños y lactantes diagnosticados con mutaciones bialélicas del gen de la otoferlina (hOTOF)
    E.2.2Secondary objectives of the trial
    •To evaluate preliminary efficacy of DB-OTO in young children and infants diagnosed with biallelic hOTOF mutations
    •Evaluar la eficacia preliminar de la DB-OTO en niños pequeños y lactantes diagnosticados con mutaciones bialélicas de hOTOF
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1.Willingness of at least 1 parent/legal guardian to provide written informed consent and willingness to comply with trial protocol
    2.Willingness of at least 1 parent/legal guardian to consent to genetic testing for the infant or child in order to evaluate a panel of hearing loss-related genes
    3.Willingness of at least 1 parent/legal guardian to consent to vaccinations for the infant or child in accordance with the country-specific pediatric immunization schedule
    4.Child/infant is 24 months of age or younger at the time of the parent/legal guardian signing the informed consent form
    5.The Investigator determines the patient is eligible for cochlear implantation
    6.Presence of biallelic, likely pathogenic or pathogenic hOTOF mutation
    7.No clinically significant laboratory findings on clinical laboratory tests at time of Screening
    8.Absence of an ABR neural signal in response to a click stimulus at or below 85 decibels normalized
    Hearing Level (dB nHL) in the ear(s) to be injected with DB-OTO
    9.DPOAE present with ≥ 6 dB signal-to-noise ratio at ≥ 3 frequencies in a distortion product (DP) Gram measured from 1 to 8 kHz in the ear(s) to be injected with DB-OTO
    10.No evidence from measures of hearing loss that show a dependence on body temperature
    11.Willingness of at least 1 parent/legal guardian to complete questionnaires at protocol-specific timepoints
    1. Disposición de al menos 1 progenitor/tutor legal para proporcionar el consentimiento informado por escrito y disposición para cumplir con el protocolo del ensayo
    2. Disposición de al menos 1 progenitor/tutor legal a dar su consentimiento para las pruebas genéticas para el bebé o niño/a con el fin de evaluar un panel de genes relacionados con la pérdida de audición
    3. Disposición de al menos 1 progenitor/tutor legal a dar su consentimiento para las vacunas del bebé o niño/a de acuerdo con el calendario de vacunación pediátrica específico del país
    4. El niño/a o lactante tiene 24 meses de edad o menos en el momento de la firma del formulario de consentimiento informado por parte del progenitor/tutor legal
    5. El investigador determina que el paciente es apto para la implantación coclear
    6. Presencia de mutación bialélica, probablemente patógena o patógena de hOTOF
    7. Sin hallazgos de laboratorio clínicamente significativos en las pruebas de laboratorio clínico en el momento de la selección
    8. Ausencia de una señal neuronal de ABR en respuesta a un estímulo de clic en el nivel de audición normalizado (dB nHL) de 85 decibelios o menos en el oído u oídos a inyectar con DB-OTO
    9. EOAPD presentes con una relación señal/ruido ≥6 dB a ≥3 frecuencias en un producto de distorsión (DP) Gram medido de 1 a 8 kHz en el/los oído(s) a inyectar con DB-OTO
    10. No hay evidencia de medidas de pérdida de audición que muestren dependencia de la temperatura corporal
    11. Disposición de al menos 1 progenitor/tutor legal para cumplimentar cuestionarios en puntos temporales específicos del protocolo
    E.4Principal exclusion criteria
    1.Presence of any disease or disorder that, in the opinion of the Investigator, would interfere with conducting the trial
    2.History of prior treatment with gene therapy
    3.Surgical anatomy that would preclude the planned surgical approach as indicated by medical imaging (eg, computed tomography [CT] or MRI) in the ear(s) to be injected with DB-OTO
    4.History or presence of any other permanent/untreatable hearing loss conditions
    5.History or presence of malignancies
    6.History or presence of meningitis
    7.History or presence of treatment with ototoxic drugs that, in the opinion of the Investigator, would interfere with conducting the trial
    8.History or presence of cochlear implants in the ear(s) to be injected with DB-OTO
    9.History of risk factor(s) for auditory neuropathy not caused by hOTOF mutations including, but not limited to, prematurity, low birth weight, hyperbilirubinemia, neonatal intensive care unit (NICU) admission, and/or low Apgar scores that, in the opinion of the Investigator, would interfere with conducting the trial
    10.Any condition that, in the opinion of the Investigator, would interfere with conducting the trial including, but not limited to, undergoing anesthesia\surgery, complying with the trial criteria, undergoing audiological assessment, and participating for the entire duration of the trial
    11.Concurrent participation in another investigational trial
    1. Presencia de cualquier enfermedad o trastorno que, en opinión del investigador, pudiera interferir con la realización del ensayo
    2. Antecedentes de tratamiento previo con terapia génica
    3. Anatomía quirúrgica que afectaría de forma significativa al enfoque quirúrgico previsto según lo indicado por las imágenes médicas (p. ej.,tomografía computarizada [TAC] o resonancia magnética [RM]) en el/los oído(s) a inyectar con DBOTO
    4. Antecedentes o presencia de cualquier otra afección de pérdida de audición permanente/no tratable
    5. Antecedentes o presencia de neoplasias malignas
    6. Antecedentes o presencia de meningitis
    7. Antecedentes o presencia de tratamiento con fármacos ototóxicos que, en opinión del investigador, interferirían en la realización del ensayo
    8. Antecedentes o presencia de implantes cocleares en el/los oído(s) a inyectar con DB-OTO
    9. Antecedentes de factor(es) de riesgo de neuropatía auditiva no causada por mutaciones en hOTOF, incluidos, entre otros, nacimiento prematuro, bajo peso al nacer, hiperbilirrubinemia, ingreso en la unidad de cuidados intensivos neonatales (UCIN) y/o puntuaciones de Apgar bajas que, en opinión del
    investigador, interferirían con la realización del ensayo
    10. Cualquier afección que, en opinión del investigador, pudiera interferir con la realización del ensayo, incluidas, entre otras, someterse a anestesia/cirugía, cumplir con los criterios del ensayo, someterse a una evaluación audiológica y participar durante todo el ensayo
    11. Participación simultánea en otro ensayo de investigación
    E.5 End points
    E.5.1Primary end point(s)
    The primary endpoint of the trial is the incidence and severity of treatment-emergent systemic and local adverse events
    El criterio principal de valoración del ensayo es la incidencia y la gravedad de los acontecimientos adversos locales y sistémicos emergentes del tratamiento
    E.5.1.1Timepoint(s) of evaluation of this end point
    Adverse events (AEs) and SAEs will be monitored and recorded at the time of signing of the informed consent throughout the Baseline, Perioperative, Short-term follow-up and Long-term follow-up period.
    Los acontecimientos adversos (EA) y los SAEs se supervisarán y registrarán en el momento de la firma del consentimiento informado durante el periodo basal, perioperatorio, de seguimiento a corto plazo y de seguimiento a largo plazo.
    E.5.2Secondary end point(s)
    Auditory brainstem response (ABR) – change in intensity threshold (decibels Hearing Level [dB nHL]) across frequency domains
    Pure-tone audiometry – change in intensity thresholds (dB HL) in treated ear across frequency domains
    Speech awareness threshold (SAT) – change in threshold in treated ear
    Respuesta auditiva del tronco cerebral (ABR): Cambio en el umbral de intensidad (decibelios Nivel auditivo [dB NHL]) en todos los dominios de frecuencia
    Audiometría de tono puro: Cambio en los umbrales de intensidad (dB HL) en el oído tratado en todos los dominios de frecuencia
    Umbral de reconocimiento del habla (SAT): Cambio en el umbral del oído tratado
    E.5.2.1Timepoint(s) of evaluation of this end point
    Subjects will undergo ABR and Efficacy assessment at Week 4 ± 3 d, Week 6± 3 d, Week 12 ± 7 d, Week 24 ± 7 d, and Week 48 ± 7 d, during short term follow-up period and every 12 months from last visit (4 years) ± 2 weeks during long term follow-up period.
    Los sujetos se someterán a una tasa de reabsorción específica y a una evaluación de la eficacia en la semana 4 ± 3 d, semana 6± 3 d, semana 12 ± 7 d, semana 24 ± 7 d,y la semana 48 ± 7 d, durante el periodo de seguimiento a corto plazo y cada 12 meses desde la última visita (4 años) ± 2 semanas durante el periodo de seguimiento a largo plazo.
    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 Yes
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others Yes
    E.6.13.1Other scope of the trial description
    Tolerability
    Tolerabilidad
    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.7.1.3.1Other 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 Yes
    E.8.1.7.1Other trial design description
    Ensayo multicéntrico con una única cohorte de dosis ascendente seguida de una cohorte de expansión b
    Multicenter Trial With a Single Ascending Dose Cohort followed by a Bilateral Expansion Cohort
    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 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 concerned3
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA5
    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 No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    United States
    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
    LVLS
    Última visita del último paciente
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years7
    E.8.9.1In the Member State concerned months5
    E.8.9.1In the Member State concerned days22
    E.8.9.2In all countries concerned by the trial years7
    E.8.9.2In all countries concerned by the trial months5
    E.8.9.2In all countries concerned by the trial days22
    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: 18
    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: 18
    F.1.1.5Children (2-11years) Yes
    F.1.1.5.1Number of subjects for this age range: 18
    F.1.1.6Adolescents (12-17 years) No
    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
    Young children and infants (2 years of age or younger) with biallelic hOTOF mutation, profound deafness presenting with absent auditory brainstem response (ABR) and present distortion product otoacoustic emission (DPOAE) will be enrolled
    Se inscribirá a niños pequeños y lactantes (2 años de edad o menos) con mutación hOTOF bialélica, sordera profunda que presenta ausencia de respuesta auditiva del tronco cerebral (ABR) y emisión otoacústica del producto de distorsión presente (DPOAE)
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state5
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 8
    F.4.2.2In the whole clinical trial 18
    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)
    Patients will be followed for a minimum of 5 years after dosing. If the patient has ended participation in the trial by reaching the last visit scheduled, then there are no plans for additional treatment or care of the participant at this time. If the participant withdraws before the end of the study, we ask that they continue to complete the safety assessments for 5 years after dosing.
    Se realizará un seguimiento de los pacientes durante un mínimo de 5 años después de la administración.Si el paciente ha finalizado la participación en el ensayo al llegar a la última visita programada, no hay planes para recibir tratamiento o atención adicionales del participante en este momento.Si el participante se retira antes de finalizar el estudio, le pedimos que continúe realizando las evaluaciones de seguridad durante 5 años después de la administración
    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 Decision2023-05-09
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2022-12-19
    P. End of Trial
    P.End of Trial StatusOngoing
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