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    Summary
    EudraCT Number:2016-003874-42
    Sponsor's Protocol Code Number:CP-4-006
    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:2017-03-14
    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 number2016-003874-42
    A.3Full title of the trial
    A phase 3, open-label, randomized, multicenter, 12 months, efficacy and safety study of weekly mod-4023 compared to daily genotropin® therapy in pre-pubertal children with growth hormone deficiency
    Estudio de fase III abierto , aleatorizado, multicéntrico, de 12 meses de
    duración, para evaluar la eficacia y seguridad de la administración semanal de
    MOD-4023 en comparación con la administración diaria de Genotropina, en
    niños prepuberales con deficiencia de hormona del crecimiento
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    An efficacy and safety study of weekly mod-4023 compared to daily genotropin® therapy in pre-pubertal children with growth hormone deficiency
    Estudio para evaluar la eficacia y seguridad de la administración semanal de
    MOD-4023 en comparación con la administración diaria de Genotropina, en
    niños prepuberales con deficiencia de hormona del crecimiento
    A.3.2Name or abbreviated title of the trial where available
    N/A
    A.4.1Sponsor's protocol code numberCP-4-006
    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 SponsorOPKO Biologics Ltd.
    B.1.3.4CountryIsrael
    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 supportOPKO Biologics Ltd.
    B.4.2CountryIsrael
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationClinical Professionals Inc
    B.5.2Functional name of contact pointClinical Trial Informaton Desk
    B.5.3 Address:
    B.5.3.1Street AddressPaseo de la Castellana 18, 7 planta
    B.5.3.2Town/ cityMadrid
    B.5.3.3Post code28046
    B.5.3.4CountrySpain
    B.5.4Telephone number34917942770
    B.5.5Fax number34917579201
    B.5.6E-mailsupport@cpiglobalcro.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community Yes
    D.2.5.1Orphan drug designation numberEU/3/12/1087
    D.3 Description of the IMP
    D.3.2Product code MOD-4023
    D.3.4Pharmaceutical form Solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSubcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNSomatrogon
    D.3.9.1CAS number 1663481-09-1
    D.3.9.2Current sponsor codeMOD-4023
    D.3.9.4EV Substance CodeSUB31414
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    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 No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product 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 Yes
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Yes
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.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 numberEU/3/12/1087
    D.3 Description of the IMP
    D.3.2Product code MOD-4023
    D.3.4Pharmaceutical form Solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSubcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNSomatrogon
    D.3.9.1CAS number 1663481-09-1
    D.3.9.2Current sponsor codeMOD-4023
    D.3.9.4EV Substance CodeSUB31414
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number50
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product 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 Yes
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Yes
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.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 Yes
    D.2.1.1.1Trade name Genotropin
    D.2.1.1.2Name of the Marketing Authorisation holderPfizer Limited
    D.2.1.2Country which granted the Marketing AuthorisationUnited Kingdom
    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 nameGenotropin
    D.3.4Pharmaceutical form Powder and solvent for solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSubcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNSomatropin
    D.3.9.1CAS number 12629-01-5
    D.3.9.3Other descriptive nameSOMATROPIN FOR INJECTION
    D.3.9.4EV Substance CodeSUB12322MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number5.3
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product 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 Yes
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Yes
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 4
    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 Yes
    D.2.1.1.1Trade name Genotropin
    D.2.1.1.2Name of the Marketing Authorisation holderPfizer Limited
    D.2.1.2Country which granted the Marketing AuthorisationUnited Kingdom
    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 nameGenotropin
    D.3.4Pharmaceutical form Powder and solvent for solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSubcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNSomatropin
    D.3.9.1CAS number 12629-01-5
    D.3.9.3Other descriptive nameSOMATROPIN FOR INJECTION
    D.3.9.4EV Substance CodeSUB12322MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number12
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product 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 Yes
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Yes
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Growth hormone deficiency in pre-pubertal children
    Deficiencia de hormona del crecimiento en niños prepuberales
    E.1.1.1Medical condition in easily understood language
    Treatment of children with growth failure due to growth hormone deficiency
    Tratamiento de niños con retraso del crecimiento por deficiencia de hormona del crecimiento
    E.1.1.2Therapeutic area Diseases [C] - Hormonal diseases [C19]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 19.1
    E.1.2Level PT
    E.1.2Classification code 10056438
    E.1.2Term Growth hormone deficiency
    E.1.2System Organ Class 10014698 - Endocrine 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 demonstrate that weekly MOD-4023 administration is non-inferior to daily Genotropin administration in terms of safety and efficacy outcomes
    Demostrar que la administración semanal de MOD-4023 es no inferior a la
    administración diaria de Genotropina en cuanto a resultados de seguridad y
    eficacia
    E.2.2Secondary objectives of the trial
    To evaluate the effect of weekly MOD-4023 and daily Genotropin administration on quality of life, as measured by the QoLISSY (Quality of Life in Short Stature Youth) at specific number of countries.
    Evaluar el efecto de la administración semanal de MOD-4023 y Genotropina
    diaria sobre la calidad de vida, según el cuestionario QoLISSY (Calidad de Vida
    de Jóvenes con Talla Baja) en un número concreto de países.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Pre-pubertal children aged ≥3 years , and not yet 11 years for girls (10 years
    and 364 days) or not yet 12 years (11 years and 364 days) for boys, (on the
    date of ICF signature), with either isolated GHD, or GH insufficiency as part
    of multiple pituitary hormone deficiency.
    2. Confirmed diagnosis of GHD by two different GH provocation tests defined
    as a peak plasma GH level of ≤10 ng/mL, determined by local or central
    laboratory using a validated assaya. Global Medical Monitor may accept
    prior local laboratory results; subject to pre-approval and if the tests were
    conducted as recommended in the protocol Appendix B.
    3. Bone age (BA) is not older than chronological age and should be less than
    10 for girls and less than 11 for boys.
    4. Without prior exposure to any rhGH therapy (naïve patients).
    5. Impaired height velocity defined as:
    -Annualized height velocity (HV) below the 25th percentile for CA (HV < -
    0.7 SDS) and gender according to Prader HV standard tables, Tanner HV
    curves, or local primary care provider standard.
    -The interval between two height measurements should be at least 6 months,
    but should not exceed 18 months prior to inclusion.
    6. BMI must be within ±2 SDS of mean BMI for the chronological age and
    sex.
    7. Baseline IGF-I level of at least 1 SD below the mean IGF-I level
    standardized for age and sex (IGF-I SDS ≤-1)a according to the central
    laboratory reference values. A single re-test will be allowed (subject to
    discussion with medical monitor) if all other criteria are met.
    8. Normal calculated GFR based on updated “bedside” Schwartz formula for
    pediatric patients (calculation is recommended below):
    CrCL (mL/min/1.73 m2) =0.413 * Ht / Scr
    Ht: height in cm;
    Scr: serum creatinine in mg/dL;
    9. Children with multiple hormonal deficiencies must be on stable replacement
    therapies (no change in dose) for other hypothalamo-pituitary organ axes for
    at least 3 months prior to ICF signing
    10. Normal 46XX karyotype for girls.
    11. Willing and able to provide written informed consent of the parent or legal
    guardian of the patient and written assent from pediatric patients (where
    applicable based on age and country regulation).
    1. Niños prepuberales de ≥ 3 años de edad, que todavía no tengan 11 años en el
    caso de las niñas (10 años y 364 días) o que todavía no tengan 12 años (11
    años y 364 días) en el caso de los niños, (en la fecha de la firma del FCI), y
    que padezcan GHD aislada, o insuficiencia de GH como parte de su
    deficiencia de hormona pituitaria múltiple.
    2. Diagnóstico confirmado de GHD mediante dos pruebas distintas de
    estimulación de la GH, definida como un nivel máximo de GH en plasma
    ≤10 ng/mL, determinado por el laboratorio local o central empleando un
    ensayo validadoa. El monitor médico global podrá aceptar resultados
    anteriores de laboratorios locales, ello sujeto a su aprobación previa y
    siempre que las pruebas se hayan llevado a cabo tal como se recomienda en
    el protocolo Anexo B.
    3. La edad ósea (EO) no debe ser superior a la edad cronológica y debe ser
    inferior a los 10 años en el caso de las niñas e inferior a 11 años en el caso
    de los niños.
    4. Sin exposición previa a ninguna terapia de rhGH (pacientes naïve).
    5. Velocidad de crecimiento deficiente, definida como:
    -Velocidad de crecimiento (VC) anualizada por debajo del percentil 25º de la
    edad cronológica EC (VC <-0,7 de PDE) y sexo según las tablas de VC de
    Prader, las curvas de VC de Tanner o el estandart para el centro sanitario.
    -El intervalo entre dos mediciones de la estatura debe ser de al menos 6
    meses, pero no debe superar los 18 meses anteriores a la inclusión.
    6. El IMC debe estar dentro del margen de ±2 respecto a la PDE del IMC
    medio para la edad cronológica y el sexo.
    7. Nivel de IGF-I basal de al menos 1 DE por debajo del nivel medio de IGF-I
    estandarizado para la edad y el sexo (PDE de IGF-I ≤-1)a según los valores
    de referencia del laboratorio central. Se permitirá una única repetición de la
    prueba (según la opinión del monitor médico) si se cumplen todos los demás
    criterios.
    8. TFG calculado normal según la fórmula de Schwartz “a pie de cama” para
    sujetos pediátricos (a continuación se recomienda la forma de calcularlo):
    CrCL (mL/min/1,73 m2) = 0,413 * Ht / Scr
    Ht: estatura en cm;
    Scr: creatinina sérica en mg/dL;
    9. Los niños con múltiples deficiencias hormonales deben estar recibiendo
    terapias de sustitución estables (sin cambios en la dosis) para otros ejes
    orgánicos hipotalámicos-pituitarios durante al menos 3 meses antes de la
    firma del FCI
    10. Cariotipo 46XX normal en el caso de las niñas.
    11. Voluntad y capacidad de facilitar el consentimiento informado por escrito
    del progenitor o tutor legal del paciente y asentimiento por escrito de los
    pacientes pediátricos (cuando corresponda según la edad y la legislación del
    país).
    E.4Principal exclusion criteria
    1. Children with prior history of leukemia, lymphoma, sarcoma or any other
    forms of cancer.
    2. History of radiation therapy or chemotherapy
    3. Malnourished children defined as BMI < -2 SDS for age and sex
    4. Children with psychosocial dwarfism
    5. Children born small for gestational age (SGA – birth weight and/or birth
    length <-2 SDS for gestational age)
    6. Presence of anti-hGH antibodies at screening
    7. Any clinically significant abnormality likely to affect growth or the ability to
    evaluate growth, such as, but not limited to, chronic diseases like renal
    insufficiency, spinal cord irradiation, etc.
    8. Type 1 and type 2 diabetic patients who, in the opinion of the investigator, are
    not receiving standard of care treatment, or are non-compliant with their
    prescribed treatment or who are in poor metabolic control.(Criteria for
    controlled diabetes are defined in Appendix F).
    9. Chromosomal abnormalities including Turner’s syndrome, Laron syndrome,
    Noonan syndrome, Prader-Willi syndrome, Russell-Silver syndrome, SHOX
    mutations/deletions and skeletal dysplasias.
    10. Concomitant administration of other treatments that may have an effect on
    growth such as anabolic steroids, or sex steroids, with the exception of
    ADHD drugs or hormone replacement therapies (thyroxin, hydrocortisone,
    desmopressin [DDAVP])
    11. Children requiring glucocorticoid therapy (e.g. for asthma) that are taking
    chronically a dose greater than 400 μg/d of inhaled budesonide or equivalent
    as provided in Appendix J.
    12. Major medical conditions and/or presence of contraindication to r-hGH
    treatment.
    13. Closed epiphyses
    14. Known or suspected HIV-positive patient, or patient with advanced diseases
    such as AIDS or tuberculosis.
    15. Drug, substance, or alcohol abuse.
    16. Known hypersensitivity to the components of study medication.
    17. Other causes of short stature such as celiac disease, uncontrolled primary
    hypothyroidism and rickets.
    18. The patient and/or the parent/legal guardian are likely to be non-compliant in
    respect to study conduct.
    19. Participation in any other trial of an investigational agent within 30 days prior
    to ICF signature (including administration of investigational agent).
    1. Niños con antecedentes de leucemia, linfoma, sarcoma o cualquier otra forma
    de cáncer.
    2. Antecedentes de radioterapia o quimioterapia
    3. Niños malnutridos, definidos como aquellos con un IMC < -2 de PDE para la
    edad y el sexo
    4. Niños con enanismo psicosocial
    5. Niños nacidos con poca talla o peso para su edad gestacional (SGA: peso al
    nacer y/o estatura al nacer <-2 de PDE para su edad gestacional)
    6. Presencia de anticuerpos anti hGH durante la selección
    7. Cualquier anomalía clínicamente significativa que tenga probabilidad de
    afectar al crecimiento o a la capacidad de evaluar dicho crecimiento, por
    ejemplo, entre otras, enfermedades crónicas como la insuficiencia renal,
    radiación de la médula espinal, etc.
    8. Pacientes diabéticos de tipo 1 y tipo 2 que, en opinión del investigador, no
    estén recibiendo el tratamiento estándar, que no cumplan su tratamiento
    prescrito o que tengan un control metabólico deficiente.(Los criterios de
    diabetes controlada se definen en el Anexo F).
    9. Anomalías cromosómicas como el síndrome de Turner, síndrome de Laron,
    síndrome de Noonan, síndrome de Prader-Willi, síndrome de Russell-Silver,
    mutaciones/deleciones del gen SHOX y displasias esqueléticas.
    10. Administración concomitante de otros tratamientos que puedan tener algún
    efecto sobre el crecimiento, como esteroides anabólicos o esteroides sexuales,
    a excepción de los fármacos ADHD o las terapias de sustitución hormonal
    (tiroxina, hidrocortisona, desmopresina [DDAVP])
    11. Niños que requieran terapia de glucocorticoides (por ejemplo, para el asma) y
    que estén tomando de forma crónica una dosis superior a los 400 μg/día de
    budesónida inhalada o algún medicamento equivalente, tal como se recoge en
    el Anexo J.
    12. Afecciones médicas importantes y/o existencia de contraindicación para el
    tratamiento con r-hGH.
    13. Epífisis cerradas
    14. Paciente diagnosticado y sospechoso de ser positivo del VIH, o paciente con
    enfermedades avanzadas como el SIDA o la tuberculosis.
    15. Alcoholismo, drogadicción o farmacoadicción.
    16. Hipersensibilidad conocida a los componentes de la medicación del estudio.
    17. Otras causas de baja estatura, como enfermedad celíaca, hipotiroidismo
    primario no controlado o raquitismo.
    18. Paciente y/o progenitor/tutor legal que pudieran ser no cumplidores con la
    realización del estudio.
    19. Participación en cualquier otro ensayo de medicamentos en fase de
    investigación dentro de los 30 días anteriores a la firma del FCI (incluida la
    administración de un fármaco en fase de investigación).
    E.5 End points
    E.5.1Primary end point(s)
    Annual Height Velocity (HV) in cm/year
    Velocidad de crecimiento (VC) anual en cm/año
    E.5.1.1Timepoint(s) of evaluation of this end point
    Baseline and after 12 months of treatment
    En el periodo de selección y tras 12 meses de tratamiento
    E.5.2Secondary end point(s)
    Secondary efficacy endpoints (Auxology/Clinical):
    • Annualized height velocity after 6 months of treatment
    • Change in height SDS at 6 and 12 months, compared to baseline
    • Change in bone maturation (BM) at the end of 12 months, compared to Screening bone age (calculated as BA/CA)
    Secondary endpoints (Biochemical):
    • Absolute IGF-I levels on day 4(-1) after MOD-4023 dosing across study visits
    • IGF-I SDS on day 4(-1) after MOD-4023 dosing across study visits
    •IGFBP-3 levels and IGFBP-3 SDS on day 4(-1) after MOD-4023 dosing across study visits
    Additional Endpoints
    •QoL endpoint measured by the QoLISSY core questionnaire at baseline and month 12 or early termination in specific countries per Appendix L.
    Objetivos de eficacia secundarios (auxología/clínicos):
    -Velocidad de crecimiento anualizada tras 6 meses de tratamiento
    -Cambio en la PDE de estatura a los 6 y 12 meses, en comparación con el
    valor basal
    -Cambio en la maduración ósea (MO) al final de los 12 meses, en
    comparación con la edad ósea obtenida en la selección (calculada como
    EO/EC)

    Objetivos secundarios (bioquímicos):
    -Niveles absolutos de IGF-I el día 4 (-1) tras la dosis de MOD-4023 a lo largo
    de las visitas del estudio
    -PDE de IGF-I el día 4 (-1) tras la dosis de MOD-4023 a lo largo de las visitas
    del estudio
    -Niveles de IGFBP-3 y PDE de IGFBP-3 el día 4 (-1) tras la dosis de MOD-
    4023 a lo largo de las visitas del estudio

    Objetivos adicionales
    -Puntuación fundamental total de CdV medida mediante el cuestionario
    QoLISSY en la visita basal y en el mes 12 o finalización precoz en países
    determinados.
    E.5.2.1Timepoint(s) of evaluation of this end point
    Indicated in E.5.2.
    Indicado en E.5.2.
    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 No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open 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) Yes
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned9
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA68
    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
    Argentina
    Australia
    Belarus
    Brazil
    Bulgaria
    Canada
    Chile
    Colombia
    France
    Georgia
    Germany
    Greece
    India
    Israel
    Italy
    Mexico
    Netherlands
    New Zealand
    Poland
    Romania
    Russian Federation
    Serbia
    Spain
    Taiwan
    Turkey
    Ukraine
    United Kingdom
    United States
    Vietnam
    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
    UVUP (ultima visita ultimo paciente)
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years2
    E.8.9.1In the Member State concerned months3
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years3
    E.8.9.2In all countries concerned by the trial months6
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 Yes
    F.1.1Number of subjects for this age range: 220
    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: 220
    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 No
    F.3.3.7Others Yes
    F.3.3.7.1Details of other specific vulnerable populations
    Children of age 3-11
    Ninos de 3-11 años
    F.4 Planned number of subjects to be included
    F.4.1In the member state28
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 68
    F.4.2.2In the whole clinical trial 220
    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)
    Standard care or participation in other study until marketing approval.
    Tratamiento estándar o participación en otro estudio hasta aprobación de comercialización.
    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 Decision2017-05-18
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2017-05-10
    P. End of Trial
    P.End of Trial StatusOngoing
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