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    Summary
    EudraCT Number:2013-001476-37
    Sponsor's Protocol Code Number:PENTA17
    National Competent Authority:Spain - AEMPS
    Clinical Trial Type:EEA CTA
    Trial Status:Restarted
    Date on which this record was first entered in the EudraCT database:2015-10-05
    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 number2013-001476-37
    A.3Full title of the trial
    SMILE: Strategy for Maintenance of HIV suppression with elvitegravir+darunavir/ritonavir in children (PENTA 17) -
    A two-arm, Phase 2/3 multicentre, open-label, randomised study evaluating safety and antiviral effect of current standard antiretroviral therapy compared to elvitegravir (EVG) administered with darunavir/ritonavir (DRV/r) in HIV-1 infected, virologically suppressed paediatric participants.
    SMILE: Estrategia para el mantenimiento de la supresión del VIH en niños con elvitegravir+darunavir/ritonavir (PENTA 17) -
    Estudio abierto aleatorizado de fase II/III, multicéntrico, con dos grupos, que evalúa la toxicidad y el efecto antiviral de las actuales terapias antirretrovirales estándares en comparación con el elvitegravir (EVG) administrado junto a darunavir/ritonavir (DRV/r) en pacientes pediátricos infectados por el VIH-1 con supresión viral.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    SMILE: Strategy for Maintenance of HIV suppression with elvitegravir+darunavir/ritonavir in children (PENTA 17)
    SMILE: Estrategia para el mantenimiento de la supresión del VIH en niños con elvitegravir+darunavir/ritonavir (PENTA 17)
    A.3.2Name or abbreviated title of the trial where available
    PENTA 17 - SMILE
    A.4.1Sponsor's protocol code numberPENTA17
    A.5.1ISRCTN (International Standard Randomised Controlled Trial) NumberISRCTN11193709
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT02383108
    A.7Trial is part of a Paediatric Investigation Plan Yes
    A.8EMA Decision number of Paediatric Investigation PlanP/310/2013
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorFondazione PENTA ONLUS
    B.1.3.4CountryItaly
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportFondazione PENTA ONLUS
    B.4.2CountryItaly
    B.4.1Name of organisation providing supportGilead Sciences International
    B.4.2CountryUnited States
    B.4.1Name of organisation providing supportJanssen-Cilag International NV
    B.4.2CountryBelgium
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationInserm SC10-US19
    B.5.2Functional name of contact pointAlexandra Compagnucci
    B.5.3 Address:
    B.5.3.1Street Address16 Avenue Paul Vaillant Couturier
    B.5.3.2Town/ cityVillejuif
    B.5.3.3Post code94807
    B.5.3.4CountryFrance
    B.5.4Telephone number0033145 59 52 90
    B.5.5Fax number0033146 58 72 93
    B.5.6E-mailalexandra.compagnucci@inserm.fr
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Norvir
    D.2.1.1.2Name of the Marketing Authorisation holderAbbVie Ltd
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.4Pharmaceutical form Film-coated 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 INNRITONAVIR
    D.3.9.1CAS number 155213-67-5
    D.3.9.4EV Substance CodeSUB10342MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number100
    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 Yes
    D.2.1.1.1Trade name Prezista
    D.2.1.1.2Name of the Marketing Authorisation holderJanssen-Cilag International NV
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.4Pharmaceutical form Film-coated 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 INNDARUNAVIR
    D.3.9.1CAS number 206361-99-1
    D.3.9.4EV Substance CodeSUB25394
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeup to
    D.3.10.3Concentration number675
    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 RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Prezista
    D.2.1.1.2Name of the Marketing Authorisation holderJanssen-Cilag International NV
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.4Pharmaceutical form Film-coated 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 INNDARUNAVIR
    D.3.9.1CAS number 206361-99-1
    D.3.9.4EV Substance CodeSUB25394
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number675
    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: 4
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Prezista
    D.2.1.1.2Name of the Marketing Authorisation holderJanssen-Cilag International NV
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.4Pharmaceutical form Film-coated 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 INNDARUNAVIR
    D.3.9.1CAS number 206361-99-1
    D.3.9.4EV Substance CodeSUB25394
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number800
    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: 5
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Vitekta
    D.2.1.1.2Name of the Marketing Authorisation holderGilead Sciences International Limited
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.2Product code GS-9137
    D.3.4Pharmaceutical form Film-coated 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 INNELVITEGRAVIR
    D.3.9.1CAS number 697761-98-1
    D.3.9.4EV Substance CodeSUB69759
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number85
    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: 6
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Vitekta
    D.2.1.1.2Name of the Marketing Authorisation holderGilead Sciences International Limited
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.2Product code GS-9137
    D.3.4Pharmaceutical form Film-coated 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 INNELVITEGRAVIR
    D.3.9.1CAS number 697761-98-1
    D.3.9.4EV Substance CodeSUB69759
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number150
    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
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Paediatric HIV-1 Infection
    Infeccion por el VIH en la poblacion pediatrica
    E.1.1.1Medical condition in easily understood language
    Paediatric HIV-1 Infection
    Infeccion por el VIH en la poblacion pediatrica
    E.1.1.2Therapeutic area Diseases [C] - Virus Diseases [C02]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 18.0
    E.1.2Level LLT
    E.1.2Classification code 10068341
    E.1.2Term HIV-1 infection
    E.1.2System Organ Class 100000004862
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To evaluate wether children with chronic HIV infection on ART with suppressed viral load will maintain similar levels of suppression with elvitegravir+ darunavir/r (EVG+DRV/r) compared to current standard of care triple ART.
    Evaluar si los niños con infección crónica por el VIH que están en tratamiento antirretroviral (TAR) y presentan supresión de la carga viral mantendrán, usando elvitegravir + darunavir/r, niveles de supresión similares a aquellos que tendrían si continuaran con el tratamiento según guías habituales.
    E.2.2Secondary objectives of the trial
    - To evaluate the PK of EVG+DRV/r
    - To evaluate the impact on clinical progression, inmmunovirological parameters, mitochondrial toxicity, lipid profile, bone mineral density, adherence, acceptability and quality of life of the Dual combination of EVG+DRV/r compared to current standard of care triple ART.
    - Evaluar los parametros FC del EVG+DRV/r
    - Evaluar el impacto en la progresión clínica, los parámetros inmunovirologicos, la toxicidad mitocondrial, el perfil lipídico, la densidad mineral ósea, la adherencia, la aceptabilidad y la calidad de vida con la terapia EVG+DRV/r en comparación con el tratamiento triterapia según guías habituales.
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    1) Pharmacokinetics (PK) Substudy
    Objectives: To determine the pharmacokinetics of darunavir (DRV), ritonavir (RTV) and elvitegravir (EVG)
    2) Mitochondrial substudy
    Objectives: To demonstrate differences in markers of mitochondrial toxicity between arms
    3) Lipids/Bone Mineral Density (BMD) substudy
    Objectives:
    - To document the development and the progression of the lipodystrophy syndrome in a subset of children
    -To evaluate the impact of ART simplification on changes of BMD in HIV-infected children.
    4) Virology
    Objectives: The laboratory tests (resistance testing & Plasma HIV-1 RNA levels or viral load) will be performed locally with the objective to study if the simplified regimen of EVG administered with DRV/r compared to standard NNRTI or PI-based 3-drug ART in HIV infected children maintain similar level of viral load.
    1) Subestudio FC
    Objectivos: Determinar los parámetros farmacocineticos del darunavir (DRV), ritonavir (RTV) y elvitegravir (EVG)
    2) Subestudio de toxicidad mitocondrial
    Objectivos: Demostrar las diferencias entre los marcadores de la toxicidad mitocondrial ente los brazos
    3) Subestudio del perfil lipídico/densidad mineral ósea (DMO)
    - Documentar el desarrollo y progresión del síndrome de lipodistrofia en un subconjunto de niños
    - Evaluar el impacto de la simplificación de TAR en los cambios de DMO en los niños infectados por VIH.
    4)Virología
    Objectivos:
    Las siguientes pruebas de laboratorio serán realizadas localmente con el objetivo de investigar si el régimen simplificado de EVG
    administrado con DRV/r comparándolo con los regímenes antirretrovirales estándar basados en 3 medicamentos (PI+2INTI o
    INNTI+2INTI) en niños infectados con el VIH mantienen similar nivel de carga viral en sangre.
    E.3Principal inclusion criteria
    1.HIV-1 infected children weighting > 17 kg at the screening visit
    2.Aged 6 to < 18 years old
    3.Parents or guardians, and children where appropriate, willing and able to give informed consent and to adhere to the protocol
    4.Children must have all HIV-1 RNA viral loads <50c/mL for at least 12 months with a minimum of two separate results before screening.
    5.Children on a 3-drug PI/r or NNRTI containing regimen for at least 6 months.
    6.Children/parents/guardians prepared to switch if randomised to elvitegravir + darunavir/ritonavir arm
    7.Children and parents prepared to restart the current ART regimen after simplification if viral load restart criteria are met
    8.For children aged 6-12 either:
    -children and caregivers are willing to participate in the lead-in PK study if the child is aged 6-12 and the PK study (for children randomised to Arm 1) is still enrolling children in their weight band OR
    - Data from the lead-in PK study have been analysed and children aged 6-12 can be enrolled directly into the main study
    1.Niños infectados por el VIH-1 con un peso igual o superior a 17 kg en el momento de la visita de selección.
    2.Niños con al menos 6 años y menores de 18 años.
    3.Los padres o tutores y los niños, si procede, están dispuestos y son capaces de dar su consentimiento informado y cumplir con el protocolo.
    4.Todos los niños deben haber tenido una carga viral VIH-1 ARN <50 c/ml durante, al menos, los últimos 12 meses, con un mínimo de dos resultados separados anteriores a la selección.
    5.Los niños deben haber seguido una pauta de tres fármacos, uno de los cuales es un IP/r o un ITIAN, durante al menos los 6 últimos meses.
    6.Los niños/padres/tutores están preparados para cambiar de tratamiento en el caso de que sean asignados aleatoriamente al grupo de elvitegravir + darunavir/ritonavir.
    7.Tras la simplificación, los niños y los padres están preparados para retomar el TAR actual si se cumplen los criterios de carga viral.
    8.Para niños con edades comprendidas entre los 6 y los 12 años, o bien:
    - los niños y sus tutores están dispuestos a participar en el estudio FC preliminar si el niño tiene entre 6 y 12 años y el estudio FC (para los pacientes randomizados en el brazo EVG/DRV/r) aún está reclutando niños en esa banda de peso, O BIEN
    - se han analizado los datos del estudio FC y los niños con edades comprendidas entre los 6 y los 12 años pueden inscribirse directamente en el estudio principal.
    E.4Principal exclusion criteria
    1.Receiving or requiring agents with interactions with darunavir, RTV, or EVG
    2.Evidence of resistance to DRV or integrase inhibitors
    3.Previous exposure to integrase inhibitors for more than 2 weeks
    4.History of previous encephalopathy
    5.Intercurrent illness
    6.Creatinine, AST or ALT of grade 3 or above at screening.
    7.Diagnosis of tuberculosis and on anti-tuberculosis treatment
    8.Hepatitis B or Hepatitis C co-infection
    9.Pregnancy or risk of pregnancy in girls of child-bearing potential unless committed to taking effective contraception
    1.Reciben o necesitan agentes que interaccionan con darunavir, RTV o EVG.
    2.Hay indicios de resistencia al DRV o a inhibidores de la integrasa.
    3.Han recibido tratamiento previo de inhibidores de la integrasa durante más de 2 semanas.
    4.Antecedente de encefalopatía.
    5.Enfermedad intercurrente.
    6.Creatinina, AST o ALT de grado 3 o superior en el momento de la selección.
    7.Diagnóstico de tuberculosis y en tratamiento para tuberculosis.
    8.Hepatitis B o coinfección con Hepatitis C.
    9.Embarazo o riesgo de embarazo en niñas en edad reproductiva, a menos que se comprometan a tomar anticonceptivos efectivos.
    E.5 End points
    E.5.1Primary end point(s)
    Percentage of patients with HIV-1 RNA ≥50 c/mL (confirmed within 4 weeks)
    Porcentaje de pacientes con VIH-1 ARN ≥50 c/ml (confirmado en 4 semanas)
    E.5.1.1Timepoint(s) of evaluation of this end point
    Any time up to week 48
    En todo momento hasta la semana 48
    E.5.2Secondary end point(s)
    -Percentage of patients with HIV-1 RNA < 50 c/mL at week 48
    -Percentage of patients with HIV-1 RNA > 50 c/mL at week 24 and week 48
    -Percentage of patients with HIV-1 RNA > 400c/mL at week 24 and week 48
    -All grade 3 or 4 clinical adverse events (particularly lipodystrophy)
    -All grade 3 or 4 laboratory adverse events
    -Any adverse event at least possibly related to study drugs or leading to treatment modifications
    -Occurrence of new major and minor resistance mutations defined by the current IAS-USA list
    -Changes in CD4 from baseline to weeks 24 and 48
    -Change in ART (defined as any change from the ART regimen at randomisation)
    -New or recurrent CDC/WHO stage C or severe stage B event or death
    -Change in blood lipids from baseline to weeks 24 and 48
    -Adherence as measured by questionnaire and visual analogue scale
    -Acceptability and quality of life over 48 weeks as assessed by patient completed questionnaires
    -Height and weight; Tanner scales (in participants aged over 8 years)
    -date of first menses
    -Porcentaje de pacientes con VIH-1 ARN <50 c/ml a la semana 48
    -Porcentaje de pacientes con VIH-1 ARN ≥50 c/ml a la semana 24 y 48
    -Porcentaje de pacientes con VIH-1 ARN ≥400 c/ml a las semanas 24 y 48
    -Todos los acontecimientos adversos de carácter clínico de grado 3 ó 4 (en particular la lipodistrofia)
    -Todos los acontecimientos adversos a nivel de laboratorio de grado 3 ó 4
    -Cualquier acontecimiento adverso que pueda estar relacionado con los fármacos del estudio o que haga necesario modificar el tratamiento
    -Aparición de nuevas mutaciones de resistencia tal como se definen en la lista IAS-USA corriente
    -Cambios en los niveles de CD4 (absolutos y porcentuales) desde el momento del inicio del estudio hasta las semanas 24 y 48
    -Modificaciones del TAR (definidos como cualquier cambio en la pauta posológica del TAR en el momento de la aleatorización)
    -Un acontecimiento nuevo o recurrente de estadio C o de estadio B grave según la CDC/OMS o un fallecimiento
    -Cambios en los parámetros lipídicos a partir del inicio hasta las semanas 24 y 48
    -Adherencia, medida a través de cuestionarios y escala análoga visual
    -Aceptabilidad y calidad de vida en el transcurso de 48 semanas, valoradas a través de los cuestionarios cumplimentados por los pacientes
    -Altura y peso; estadios de Tanner (en los pacientes de más de 8 años)
    -Fecha de la primera menstruación
    E.5.2.1Timepoint(s) of evaluation of this end point
    At several time during the trial depending the secondary enpoints (Describe in E.5.2)
    En varias veces durante el ensayo segun los criterios secundarios de valoración (ver 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 Yes
    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) Yes
    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 Yes
    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 concerned10
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA40
    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
    Belgium
    Brazil
    Denmark
    France
    Germany
    Ireland
    Italy
    Mexico
    Netherlands
    Poland
    Portugal
    Romania
    South Africa
    Spain
    Sweden
    Switzerland
    Thailand
    Uganda
    Ukraine
    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
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years
    E.8.9.1In the Member State concerned months30
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial months30
    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: 300
    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) Yes
    F.1.1.6.1Number of subjects for this age range: 180
    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 Yes
    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
    Children under 18 years old.
    Ninos menos de 18 anos.
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state35
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 100
    F.4.2.2In the whole clinical trial 300
    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)
    Drugs will be supplied by collaborating pharmaceutical companies or PENTA free of charge to participants deriving benefit until they become available locally.
    Las compañías farmacéuticas colaboradoras o PENTA suministrarán los fármacos a los participantes de forma gratuita hasta que estos estén disponibles a nivel local.
    G. Investigator Networks to be involved in the Trial
    G.4 Investigator Network to be involved in the Trial: 1
    G.4.1Name of Organisation Inserm SC10-US19
    G.4.3.4Network Country France
    G.4 Investigator Network to be involved in the Trial: 2
    G.4.1Name of Organisation MRC CTU
    G.4.3.4Network Country United Kingdom
    G.4 Investigator Network to be involved in the Trial: 3
    G.4.1Name of Organisation PHPT-IRD 174
    G.4.3.4Network Country Thailand
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2015-12-16
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2015-11-05
    P. End of Trial
    P.End of Trial StatusRestarted
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