Flag of the European Union EU Clinical Trials Register Help

Clinical trials

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


    The EU Clinical Trials Register currently displays   41232   clinical trials with a EudraCT protocol, of which   6757   are clinical trials conducted with subjects less than 18 years old.
    The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).


    Phase 1 trials conducted solely in adults and that are not part of an agreed PIP are not public in the EU CTR (refer to European Guidance 2008/C 168/02   Art. 3 par. 2 and   Commission Guideline 2012/C 302/03,   Art. 5) .
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Print Download

    Summary
    EudraCT Number:2017-002704-27
    Sponsor's Protocol Code Number:VBP15-004
    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:2019-06-11
    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 number2017-002704-27
    A.3Full title of the trial
    A Phase IIb Randomized, Double-blind, Parallel Group, Placebo- and Active-controlled Study with Double-Blind Extension to Assess the Efficacy and Safety of Vamorolone in Ambulant Boys with Duchenne Muscular Dystrophy (DMD)
    Un estudio fase IIb aleatorizado, doble ciego, con grupo paralelo, controlado con placebo y sustancia activa con extensión doble ciego para evaluar la eficacia y seguridad de la vamorolona en niños ambulantes con distrofia muscular de Duchenne (DMD)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Study to Assess the efficacy and the safety of Vamorolone in Boys with Duchenne Muscular Dystrophy (DMD)
    Estudio para evaluar la eficacia y la seguridad de vamorolone en niños con distrofia muscular de Duchenne (DMD)
    A.3.2Name or abbreviated title of the trial where available
    VISION DMD
    A.4.1Sponsor's protocol code numberVBP15-004
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT03439670
    A.5.4Other Identifiers
    Name:FDA IND NumberNumber:118942
    A.7Trial is part of a Paediatric Investigation Plan Yes
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorReveraGen BioPharma, Inc.
    B.1.3.4CountryUnited States
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportEuropean Commission (H2020 Grant)
    B.4.2CountryBelgium
    B.4.1Name of organisation providing supportReveraGen BioPharma, Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationPSR Group B.V.
    B.5.2Functional name of contact pointChrista van Kan
    B.5.3 Address:
    B.5.3.1Street AddressAntareslaan 41
    B.5.3.2Town/ cityHoofddorp
    B.5.3.3Post code2132 JE
    B.5.3.4CountryNetherlands
    B.5.4Telephone number+31 23 303 6900
    B.5.6E-mailchrista.vankan@psr-group.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 numberEMA/OD/049/14
    D.3 Description of the IMP
    D.3.1Product nameVamorolone
    D.3.2Product code VBP15
    D.3.4Pharmaceutical form Oral suspension
    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 INNVAMOROLONE
    D.3.9.1CAS number 13209-41-1
    D.3.9.2Current sponsor codeVBP15
    D.3.9.4EV Substance CodeSUB188638
    D.3.10 Strength
    D.3.10.1Concentration unit % (W/W) percent weight/weight
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number1.33
    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 No
    D.3.11.3.2Gene therapy medical product No
    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.IMP: 2
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community Yes
    D.2.5.1Orphan drug designation numberEMA/OD/049/14
    D.3 Description of the IMP
    D.3.1Product nameVamorolone
    D.3.2Product code VBP15
    D.3.4Pharmaceutical form Oral suspension
    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 INNVAMOROLONE
    D.3.9.1CAS number 13209-41-1
    D.3.9.2Current sponsor codeVBP15
    D.3.9.4EV Substance CodeSUB188638
    D.3.10 Strength
    D.3.10.1Concentration unit % (W/W) percent weight/weight
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number4
    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 No
    D.3.11.3.2Gene therapy medical product No
    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.IMP: 3
    D.1.2 and D.1.3IMP RoleComparator
    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 namePrednisone
    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 INNPREDNISONE
    D.3.9.1CAS number 53-03-2
    D.3.9.3Other descriptive namePREDNISONE
    D.3.9.4EV Substance CodeSUB10020MIG
    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 No
    D.3.11.3.2Gene therapy medical product No
    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
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboOral suspension
    D.8.4Route of administration of the placeboOral use
    D.8 Placebo: 2
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboTablet
    D.8.4Route of administration of the placeboOral use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Duchenne muscular dystrophy (DMD)
    Distrofia Muscular de Duchenne (DMD)
    E.1.1.1Medical condition in easily understood language
    Duchenne muscular dystrophy (DMD)
    Distrofia Muscular de Duchenne (DMD)
    E.1.1.2Therapeutic area Diseases [C] - Musculoskeletal Diseases [C05]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level PT
    E.1.2Classification code 10013801
    E.1.2Term Duchenne muscular dystrophy
    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
    1. To compare the efficacy of vamorolone administered orally at daily doses of 2.0 mg/kg and 6.0 mg/kg over a 24-week treatment period vs. placebo in ambulant boys ages 4 to <7 years with DMD; and

    2. To evaluate the safety and tolerability of vamorolone administered orally at daily doses of 2.0 mg/kg and 6.0 mg/kg in ambulant boys ages 4 to <7 years with DMD.
    1. Comparar la eficacia de vamorolone administrado por vía oral en dosis diarias de 2 mg/kg y 6 mg/kg durante un periodo de 24 semanas con el uso de un placebo en niños con movilidad a partir de 4 años de edad y menores de 7 con DMD;

    2. Evaluar la seguridad y tolerabilidad de vamorolone administrado por vía oral en dosis diarias de 2 mg/kg y 6 mg/kg en niños con movilidad a partir de 4 años de edad y menores de 7 con DMD.
    E.2.2Secondary objectives of the trial
    1. & 2. To compare the safety (secondary obj. 1.) and efficacy (secondary obj. 2.) of vamorolone administered orally at daily doses of 2.0 mg/kg and 6.0 mg/kg over a 24-wk treatment period vs. daily prednisone 0.75 mg/kg in ambulant boys ages 4 to <7 years with DMD;
    3. To compare the efficacy of vamorolone administered orally at daily doses of 2.0 mg/kg vs. vamorolone administered orally at daily doses of 6.0 mg/kg over a 24-wk treatm. period in ambulant boys ages 4 to <7 years with DMD;
    4. & 5. To compare the efficacy (secondary obj. 4.) and the safety (secondary obj. 5.) of vamorolone administered orally at daily doses of 2.0 mg/kg and 6.0 mg/kg over a 48-wk treatm. period in ambulant boys ages 4 to <7 years with DMD vs. respectively untreated DMD historical controls and prednisone-treated DMD historical controls;
    6. To evaluate the population pharmacokinetics of vamorolone administered orally at daily doses of 2.0 mg/kg and 6.0 mg/kg in ambulant boys ages 4 to <7 years with DMD.
    1 & 2. Comparar la seguridad (objetivo sec .1) y eficacia (objetivo sec .2) de vamorolone por vía oral en dosis diarias de 2 mg/kg y 6 mg/kg durante 24 semanas con el uso diario de prednisona en una dosis de 0,75 mg/kg en niños con movilidad a partir de 4 años de edad y menores de 7 con DMD;
    3. Comparar la eficacia de vamorolone por vía oral en dosis diarias de 2 mg/kg con vamorolone por vía oral en dosis diarias de 6 mg/kg durante 24 semanas en niños con movilidad a partir de 4 años de edad y menores de 7 con DMD;
    4&5. Comparar la eficacia (objetivo sec .4 y eficacia (objetivo sec .5) de vamorolone por vía oral en dosis diarias de 2 mg/kg y 6 mg/kg durante 48 semanas en niños con movilidad a partir de 4 años de edad y menores de 7 con DMD con respecto a controles históricos de DMD sin tratamiento;
    6. Evaluar la farmacocinética poblacional (PK) de vamorolone administrado por vía oral en dosis diarias de 2 mg/kg y 6 mg/kg en niños ambulatorios de 4-7 años edad con DMD.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Subject’s parent(s) or legal guardian(s) has (have) provided written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization, where applicable, prior to any study-related procedures; participants will be asked to give written or verbal assent according to local requirements
    2. Subject has a centrally confirmed (by TRiNDS central genetic counselor[s]) diagnosis of DMD as defined as:
    • Dystrophin immunofluorescence and/or immunoblot showing complete dystrophin deficiency, and clinical picture consistent with typical DMD, OR
    • Identifiable mutation within the DMD gene (deletion/duplication of one or more exons), where reading frame can be predicted as 'out-of-frame', and clinical picture consistent with typical DMD, OR
    • Complete dystrophin gene sequencing showing an alteration (point mutation, duplication, other) that is expected to preclude production of the dystrophin protein (i.e. nonsense mutation, deletion/duplication leading to a downstream stop codon), with a clinical picture consistent with typical DMD;
    3. Subject is ≥4 years and <7 years of age at time of enrollment in the study;
    4. Subject weighs >13.0 kg and ≤39.9 kg at the Screening Visit;
    5. Subject is able to walk independently without assistive devices;
    6. Subject is able to complete the Time to Stand Test (TTSTAND) without assistance in <10 seconds, as assessed at the Screening Visit;
    7. Clinical laboratory test results are within the normal range at the Screening Visit, or if abnormal, are not clinically significant, in the opinion of the Investigator. [Note: Serum gamma glutamyl transferase (GGT), creatinine, and total bilirubin all must be ≤ upper limit of the normal range at the Screening Visit];
    8. Subject has evidence of chicken pox immunity as determined by presence of IgG antibodies to varicella, as documented by a positive test result from the local laboratory at the Screening Visit;
    9. Subject is able to swallow tablets, as confirmed by successful test aswallowing of placebo tablets during the Screening Period; and
    10. Subject and parent(s)/guardian(s) are willing and able to comply with scheduled visits, study drug administration plan, and study procedures.
    1. Los padres o tutores legales del participante han hecho entrega de su consentimiento informado por escrito y de la autorización que establece la Ley Británica de Portabilidad y Responsabilidad de Seguros Médicos (HIPAA, por sus siglas en inglés), si procediese, antes de que se lleve a cabo cualquier procedimiento relacionado con el estudio; los participantes deberán dar su consentimiento, de modo verbal o por escrito, de acuerdo con los requisitos locales.
    2. El participante cuenta con un diagnóstico de DMD (confirmado por un asesor genético central de TRiNDS) tal y como se define a continuación:
    • Inmunofluorescencia y/o inmunoblot de la distrofina que muestre una deficiencia total de distrofina y un cuadro clínico que coincida con una DMD típica, O
    • Una mutación identificable del gen de la DMD (borrado/duplicado de uno o más exones), donde el marco de lectura pueda predecirse como “fuera del marco” y el cuadro clínico coincida con una DMD típica, O
    • Una secuenciación completa del gen de la distrofina que muestre una alteración (mutación puntual, duplicado, etc.) que se espera que impida la producción de la proteína distrofina (es decir, una mutación sin sentido, un borrado/duplicado que conduzca a un codón de terminación descendiente), con un cuadro clínico que se corresponda con el de una DMD típica.
    3. La edad del sujeto es igual o mayor de 4 años y menor de 7 en el momento de reclutarle como participante en el estudio;
    4. El peso del sujeto es superior a 13 kg e inferior o igual a 39,9 kg en la fecha de la visita de Visita de Pre-selección;
    5. El sujeto es capaz de caminar por sí solo sin la ayuda de dispositivos de asistencia;
    6. El sujeto es capaz de completar la prueba de Tiempo para Levantarse (Time to Stand Test [TTSTAND]) sin ayuda en menos de 10 segundos, tal y como se comprobará en la Visita de Exploración;
    7. Los resultados clínicos de las pruebas de laboratorio se encuentran dentro del rango normal en la Visita de Pre-selección, o si estos fuesen anormales, no son clínicamente significativos en la opinión del Investigador. [Nota: La GGT sérica, la creatinina y el nivel total de bilirrubina deberán ser inferiores o iguales al límite superior del rango normal en la Visita de Pre-selección];
    8. El sujeto presenta una inmunidad comprobada al sarampión, tal y como lo evidencia la presencia de anticuerpos de IgG a la varicela y como se demuestra en un test de resultado positivo llevado a cabo por el laboratorio del centro local en la Visita de Pre-selección;
    9. El sujeto es capaz de tragar comprimidos, tal y como se demostró en el test de tragar comprimidos de placebo que se llevó a cabo durante la Visita de Pre-selección; y
    10. El sujeto y sus padres/tutores legales están dispuestos y capacitados para cumplir con el calendario de visitas programadas, con el plan de administración del fármaco objeto de estudio y con los procedimientos requeridos por el estudio.
    E.4Principal exclusion criteria
    1. Subject has current or history of major renal or hepatic impairment, diabetes mellitus or immunosuppression;
    2. Subject has current or history of chronic systemic fungal or viral infections;
    3. Subject has had an acute illness within 4 weeks prior to the first dose of study medication;
    4. Subject has used mineralocorticoid receptor agents, such as spironolactone, eplerenone, canrenone (canrenoate potassium), prorenone (prorenoate potassium), mexrenone (mexrenoate potassium) within 4 weeks prior to the first dose of study medication;
    5. Subject has a history of primary hyperaldosteronism;
    6. Subject has evidence of symptomatic cardiomyopathy [Note: Asymptomatic cardiac abnormality on investigation would not be exclusionary];
    7. Subject is currently being treated or has received previous treatment with oral glucocorticoids or other immunosuppressive agents [Notes: Past transient use of oral glucocorticoids or other oral immunosuppressive agents for no longer than 1 month cumulative, with last use at least 3 months prior to first dose of study medication, will be considered for eligibility on a case-by-case basis, unless discontinued for intolerence. Inhaled and/or topical glucocorticoids are permitted if last use is at least 4 weeks prior to first dose of study medication or if administered at stable dose beginning at least 4 weeks prior to first dose of study medication and anticipated to be used at the stable dose regimen for the duration of the study];
    8. Subject has an allergy or hypersensitivity to the study medication or to any of its constituents;
    9. Subject has used idebenone within 4 weeks prior to the first dose of study medication;
    10. Subject has severe behavioural or cognitive problems that preclude participation in the study, in the opinion of the Investigator;
    11. Subject has previous or ongoing medical condition, medical history, physical findings or laboratory abnormalities that could affect safety, make it unlikely that treatment and follow-up will be correctly completed or impair the assessment of study results, in the opinion of the Investigator;
    12. Subject is taking (or has taken within 4 weeks prior to the first dose of study medication) herbal remedies and supplements which can impact muscle strength and function (e.g. Co-enzyme Q10, Creatine, Proglandine etc);
    13. Subject is taking (or has taken within 3 months prior to the first dose of study medication) any medication indicated for DMD, including Exondys51 and Translarna;
    14. Subject has been administered a live attenuated vaccine within 14 days prior to the first dose of study medication;
    15. Subject is currently taking any other investigational drug or has taken any other investigational drug within 3 months prior to the first dose of study medication;
    16. Subject has a sibling who is currently enrolled in any vamorolone study or Expanded Access Program, or who intends to enroll in any vamorolone study or Expanded Access Program during the subject’s participation in the VBP15-004 study; or
    17. Subject has previously been enrolled in the study.
    Note: Any parameter/test may be repeated at the Investigator’s discretion during Screening to determine reproducibility. In addition, subjects may be rescreened if ineligible due to a transient condition which would prevent the subject from participating, such as an upper respiratory tract infection or injury, or if ineligible due to negative anti-varicella IgG antibody test result.
    1. El sujeto presenta o ha sufrido en el pasado una disfunción renal o hepática severa, diabetes mellitus o una inmunosupresión;
    2. El sujeto sufre o ha sufrido en el pasado una infección crónica sistémica de tipo fúngica o viral;
    3. El sujeto ha sufrido una enfermedad aguda en las 4 semanas previas a la primera dosis del fármaco objeto de estudio;
    4. El sujeto ha tomado agentes receptores mineralocorticoides, tales como espironolactona, eplerenona, canrenona (canrenoato potásico), prorenona (prorenoato potásico) o mexrenona (mexrenoato potásico) en las 4 semanas previas a la primera dosis del fármaco objeto de estudio;
    5. El sujeto tiene antecedentes de hiperaldosteronismo primario;
    6. El sujeto presenta muestras de cardiomiopatía sintomática [Nota: una anomalía cardíaca asintomática detectada durante la investigación no supondría un motivo de exclusión];
    7. El sujeto está actualmente bajo tratamiento (o lo ha estado en el pasado) con glucocorticoides por vía oral u otros agentes inmunosupresores [Notas: La participación de sujetos que hubiesen usado de forma temporal en el pasado glucocorticoides inhalados o por vía oral u otros agentes inmunosupresores por vía oral durante un periodo inferior a 1 mes acumulado, con la última toma al menos 3 meses antes de la primera dosis del fármaco objeto de estudio, será evaluada según el caso específico, a menos que se hubiese suspendido dicho tratamiento por razones de intolerancia. El uso de glucocorticoides inhalados o tópicos está permitido siempre que su última toma haya tenido lugar como mínimo 4 semanas antes de la primera dosis del fármaco objeto de estudio, o en caso de administrarse en dosis estables, siempre que se haya iniciado el tratamiento como mínimo 4 semanas antes de la primera dosis del fármaco objeto de estudio y que vaya a ser administrado en un régimen de dosis estable durante el transcurso del estudio];
    8. El sujeto es alérgico o hipersensible al fármaco objeto de estudio o a alguno de sus componentes;
    9. El sujeto ha consumido idebenona en las 4 semanas anteriores a la primera toma del fármaco objeto de estudio;
    10. El sujeto tiene problemas conductuales o cognitivos que, en la opinión del Investigador, impiden su participación en el estudio;
    11. El sujeto presenta o ha presentado un problema médico, antecedentes médicos, manifestaciones físicas o anomalías de laboratorio que pueden afectar a su seguridad, pueden impedir la correcta administración y seguimiento del tratamiento o dificultar la evaluación de los resultados del estudio, siempre según el criterio del Investigador;
    12. El sujeto está tomando (o ha tomado en las 4 semanas anteriores a la primera dosis del fármaco objeto de estudio) remedios herbales y suplementos que puedan afectar a su fuerza y función muscular (por ejemplo, co-enzima Q10, creatina, etc.);
    13. El sujeto está tomando (o ha tomado en los 3 meses previos a la primera dosis del fármaco objeto de estudio) cualquier medicación indicada para el tratamiento de DMD, incluidas Exondys51 y Translarna;
    14. El sujeto ha recibido una vacuna viva atenuada en los 14 días previos a la primera dosis del fármaco objeto de estudio;
    15. El sujeto está tomando cualquier otro fármaco experimental dentro de los tres meses previos a la primera dosis del fármaco objeto de estudio;
    16. El sujeto tiene un hermano/hermana que participa actualmente (o tiene intención de hacerlo) en un estudio sobre vamorolone o en un Programa de Acceso Ampliado durante la participación del sujeto en el estudio VBP15-004; o
    17. El sujeto ha participado anteriormente en el estudio.
    Nota: Cualquier parámetro o prueba podrá repetirse si así lo considera el Investigador durante la Visita de Pre-selección con el objetivo de determinar su reproducibilidad. Además, los sujetos que hubiesen sido excluidos a causa de un problema médico transitorio que impidiese su participación (por ejemplo, por una infección del tracto respiratorio superior, por una lesión o por un resultado negativo en la prueba de anticuerpos de IgG anti-varicela) podrán ser explorados y examinados de nuevo.
    E.5 End points
    E.5.1Primary end point(s)
    Primary Clinical Efficacy Endpoint
    1. Time to Stand Test (TTSTAND) velocity (rise/second): Comparison of each vamorolone dose level group versus the placebo group in change from baseline to the Week 24 assessment.

    For Safety Endpoints and Pharmacodynamic Endpoints see E.5.2
    Variable principal de Eficacia:
    1.- Tiempo para levantarse (TTSTAND): comparación de los cambio de cada uno de los grupos de dosis de vamorolone versus el el grupo de placebo desde la evaluación basal hasta la Semana 24.

    Para ver las Variables secundarias de Seguridad y Farmacodinámicas refiérase a E.5.2
    E.5.1.1Timepoint(s) of evaluation of this end point
    Week 24
    Semana 24
    E.5.2Secondary end point(s)
    Secondary Efficacy Endpoints
    1. Change from baseline to each of the scheduled study assessment time points for each treatment group up to Week 48, with comparison of each vamorolone dose level group versus the placebo group at each of the scheduled study assessment time points up to and including Week 24 for:
    • Time to Stand Test (TTSTAND) velocity (rise/second) (other than Week 24);
    • Time to Climb (4 Steps) Test (TTCLIMB) velocity (tasks/second);
    • Time to Run/Walk Test (TTRW) velocity (meters/second) to complete 10 meters of a 14 meter course;
    • Total distance traveled, in meters, in completing the Six-minute Walk Test (6MWT);
    • North Star Ambulatory Assessment (NSAA);
    • Hand-held myometry (elbow flexors and knee extensors); and
    • Range of motion in the ankles (ROM).
    2. Change from baseline with comparison of each vamorolone dose level group versus the prednisone group at each of the scheduled study assessment time points up to and including Week 24 for:
    • Total distance traveled, in meters, in completing the Six-minute Walk Test (6MWT).

    Safety Endpoints
    1. BMI z-score: Comparison of each vamorolone dose level group with the prednisone group in change from baseline to each of the scheduled on-treatment and post-treatment time points.
    2. Treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) by system organ class (SOC): Overall by treatment, by treatment and relationship, and by treatment and intensity;
    3. Vital signs (sitting blood pressure, heart rate, respiratory rate, and body temperature): Change from baseline to each of the scheduled on-treatment and post-treatment assessment time points;
    4. Body weight and height: Change from baseline to each of the scheduled on-treatment and post-treatment assessment time points;
    5. Cushingoid features: Change from baseline to each of the scheduled on-treatment and post-treatment assessment time points (changes from baseline will be recorded as AEs);
    6. Clinical laboratory values: Change from baseline to each of the scheduled on-treatment and post-treatment assessment time points in:
    • Hematology and clinical chemistry
    • Lipid profile (triglycerides, total cholesterol, low density lipoprotein [LDL], high density lipoprotein [HDL])
    • Vitamin D level
    • Urinalysis;
    7. 12-lead electrocardiogram (ECG): Change from baseline to each of the scheduled on-treatment and post-treatment assessment time points;
    8. 2D-echocardiogram: Change from baseline to Week 24 and Week 48;
    9. Dual-energy x-ray absorptiometry (DXA) scan: Change from baseline to Week 24 and Week 48 in spine BMD, spine BMD Z-score, total body BMD, spine and total body bone mass, and total body composition (lean mass, fat mass, fat-free mass, Lean Mass Index, and Fat Mass Index);
    10. Spine x-rays: Change from baseline to Week 24 assessment;
    11. Eye examination for detection of clinically significant abnormalities (cataracts and/or glaucoma) at Week 24 and Week 48 assessments compared to baseline;
    12. ACTH stimulation Test: measure of adrenal insufficiency at Week 24 and Week 48. Adrenal insufficiency is likely if cortisol levels <18 μg/dL (or 500 nM) 30 or 60 minutes after stimulation with Cosyntropin.

    Pharmacodynamic Endpoints
    1. The following pharmacodynamic biomarkers are considered secondary outcome measures focusing on safety outcomes. In each case, the biomarkers studied reflect safety concerns of glucocorticoids:
    a. Adrenal suppression. First-in-morning serum cortisol levels will be measured. Cortisol measures falling below 3.6 μg/dL (or 100 nM) will be considered to be indicative of the development of adrenal suppression. ACTH stimulation test will be performed at the Screening Visit and at the Week 24 Follow-up Visit (48 ± 3 hours after the final dose of Treatment Period #1 study medication) and at the Week 48 Follow-up Visit (48 ± 3 hours after the final dose of Treatment Period #2 study medication): cortisol levels <18 μg/dL (or 500 nM) 30 or 60 minutes after stimulation with Cosyntropin (250 μg) will be considered to be indicative of adrenal insufficiency.
    b. Bone turnover. Measures of serum osteocalcin are reflective of bone formation, and measures of serum CTX1 are reflective of bone reabsorption. Ratios of osteocalcin and CTX1 predict later clinical safety concerns of osteopenia and bone fragility.
    c. Insulin resistance. Glucocorticoids cause both acute and chronic insulin resistance, with serum elevations of both insulin and glucose. Measures of hyperinsulinemia and hyperglycemia are accepted measures of insulin resistance.
    d. Immune suppression. Glucocorticoids can cause immunosuppression. Measure of differential lymphocyte percentage can be a biomarker for immune suppression.
    2. Exploratory biomarkers for aspects of safety and efficacy.
    DE EFICACIA
    1. Cambios desde el punto basal para cada una de las evaluaciones del estudio para cada grupo de tratamiento hasta la semana 48, en comparación con cada grupo de dosis de vamorolone vs el grupo de placebo en cada punto de evaluación programado en el estudio hasta la semana 24 (incluida) para:
    • Prueba de tiempo para levantarse (TTSTAND) (diferente a la semana 24);
    • Prueba de tiempo para subir 4 escalones (TTCLIMB);
    • Prueba de tiempo para correr/caminar 10 metros (TTRW);
    • Prueba de caminar durante 6 minutos (6MWT);
    • Evaluación de la Movilidad North Star (NSAA);
    • Miometría manual (flexores del codo/ extensores de rodilla);
    • Amplitud de movimiento de los tobillos (ROM)

    2. Cambios desde el punto basal con comparación de cada grupo de dosis de vamorolone vs el grupo de prednisona en cada punto de evaluación programado en el hasta la semana 24 (incluida) para:
    • Distancia total recorrida (en metros) en la prueba 6MWT;

    DE SEGURIDAD
    1. IMC z-score: Comparación del cambio de cada grupo de dosis de vamorolone con el grupo de prednisona con respecto al basal para cada una de las evaluaciones previstas durante el tratamiento y después del tratamiento;
    2. Acontecimientos adversos emergentes asociados al tratamiento (TEAEs) y acontecimientos adversos graves (SAEs) clasificados por la clase de sistema orgánico (SOC): global por tratamiento, por tratamiento y relación, y por tratamiento e intensidad;
    3. Constantes vitales: Cambios con respecto al momento basal para cada una de las evaluaciones previstas durante el tratamiento y después del tratamiento;
    4. Peso corporal y altura: Cambios con respecto al momento basal para cada una de las evaluaciones previstas durante el tratamiento y después del tratamiento;
    5. Rasgos Cushingoides: Cambio con respecto al momento basal para cada una de las evaluaciones previstas durante el tratamiento y después del tratamiento (los cambios se registrarán como AEs);
    6. Valores del laboratorio clínico: Cambios con respecto al momento basal basal para cada una de las evaluaciones previstas durante el tratamiento y después del tratamiento para:
    o Hematología y Bioquímica
    o Análisis de orina
    o Perfil de lípidos
    o Vitamina D
    7. ECG 12 derivaciones: cambios con respecto al basal en cada momento de evaluación previsto durante el tratamiento y después del tratamiento;
    8. Ecocardiografía 2D: cambio desde el punto basal hasta la semana 24 y 48;
    9. Densitometría (DXA): Cambio desde el momento basal hasta la semana 24 y 48 en la densidad ósea de la columna vertebral, de la columna vertebral Z-score, total del cuerpo, masa ósea de la columna vertebral y total del cuerpo, y la composición total del cuerpo (masa magra, masa grasa, masa libre de grasa, índice de masa magra y el índice de masa grasa);
    10. RX de la columna vertebral: Cambios desde el momento basal hasta la evaluación de la semana 24;
    11. Exploración ocular para detectar anomalías clínicamente significativas (cataratas y/o glaucoma) en la semana 24 y 48 en comparación con el momento basal;
    12. Prueba de estimulación de ACTH: evaluación de insuficiencia adrenal en la semana 24 y 48. Se considera insuficiencia adrenal si los niveles de cortisol <18 μg/dL (o 500 nM) 30 ó 60 minutos después de la estimulación con Cosintropina.

    DE FARMACODINÁMICA
    1. Los siguientes biomarcardores farmacodinámicos se consideran variables secundarias centrándose en los resultados de seguridad. En cada caso, los biomarcadores estudiados reflejan preocupaciones por la seguridad de los glucocorticoides:
    a. Supresión Adrenal. Se medirán los primeros niveles de cortisol en suero en la mañana. Si cortisol < de 3,6 μg/dL (o 100 nM) se considerará indicativo del desarrollo de supresión suprarrenal. La prueba de estimulación de ACTH se realizará durante la visita de Pre-selección y la semana 24 de seguimiento (48 ± 3 horas después de la última dosis del fármaco del Periodo de Tratamiento #1) y la visita de la semana 48 de seguimiento (48 ± 3 horas después de la última dosis del fármaco del Periodo de Tratamiento #2): los niveles de cortisol < 18 μg/dL (o 500 nM) 30 ó 60 minutos después de la estimulación con Cosyntropina (250 μg) se considerarán indicativos de insuficiencia suprarrenal.
    b. Recambio óseo. La medida de osteocalcina sérica refleja la formación ósea, y la medida de CTX1 suero refleja la reabsorción ósea. Los ratios de osteocalcina y CTX1 predicen preocupaciones por la seguridad clínica de la fragilidad del hueso y osteopenia.
    c. Resistencia a Insulina. Los glucocorticoides causan tanto resistencia a la insulina aguda como crónica, con elevaciones de tanto insulina como glucosa en sangre. Se aceptan las medidas de hiperinsulinemia e hiperglucemia como resistencia a insulina.
    d. Supresión inmune. Los glucocorticoides pueden causar inmunosuppresión. La medida del porcentaje diferencial de linfocitos puede ser un biomarcador de supresión inmune.
    2. Biomarcadores exploratorios para seguridad y eficacia.
    E.5.2.1Timepoint(s) of evaluation of this end point
    Weeks 24 and 48
    Semanas 24 y 48
    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 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) 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) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    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 Yes
    E.8.1.6Cross over No
    E.8.1.7Other Yes
    E.8.1.7.1Other trial design description
    En la semana 28, los sujetos en los brazos de prednisona o placebo cambian a VBP15 (2 ó 6 mg/kg)
    At week 28, subjects in prednisone or placebo arm switch to VBP15 (2 or 6 mg/kg) daily for 20 weeks
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) Yes
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial6
    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 concerned2
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA18
    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
    Australia
    Belgium
    Canada
    Czech Republic
    Germany
    Greece
    Israel
    Italy
    Netherlands
    Spain
    Sweden
    United Kingdom
    United States
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    LVLS
    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 months10
    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 months3
    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.1.1Number of subjects for this age range: 120
    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.1.1.5.1Number of subjects for this age range: 120
    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 No
    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
    There is an information leaflet & consent form for the parents. The children will have an illustrated information letter and an assent form (Age 4: pictures only, Age 5-6: 4 pg information leaflet).
    Existe una Hoja de Información y formulario de consentimiento para los padres. Los niños tendrán una carta con la información en dibujos y un formulario de asentimiento (edad 4 años: solo dibujos; edad 5-6 años dibujos y texto sencillo)
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state8
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 72
    F.4.2.2In the whole clinical trial 120
    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)
    Subjects who complete the VBP15-004 study will be given the option of continuing vamorolone treatment in a long-term extension study under separate protocol (VBP15-005). Subjects who will not continue vamorolone treatment in VBP15-005, including those subjects who will transition to standard of care treatment for DMD, will have their vamorolone dose tapered during a 4-week dose-tapering period, prior to discharge from the study.
    Los sujetos que completen el estudio VBP15-004 tendrán la opción de continuar el tratamiento de vamorolone en un estudio de extensión a largo plazo bajo un protocolo separado (VBP15-005). Los sujetos que no continúen el tratamiento con vamorolone en el estudio VBP15-005, incluidos aquellos que hagan la transición al estándar de tratamiento para la DMD, tendrán un periodo de disminución gradual de la dosis de vamorolone durante 4 semanas, antes de finalizar el estudio.
    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 Decision2019-08-13
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2019-07-24
    P. End of Trial
    P.End of Trial StatusOngoing
    For support, visit the EMA Service Desk , log in using your EMA account and open a ticket specifying "EU CTR" in your request.
    If you do not have an account, please visit the EMA Account management page page click on "Create an EMA account" and follow the instructions.
    The status of studies in GB is no longer updated from 1.1.2021
    For the UK, as from 1.1.2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2021 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA