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The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
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  • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).


    The EU Clinical Trials Register currently displays   43851   clinical trials with a EudraCT protocol, of which   7283   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
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    Summary
    EudraCT Number:2020-001426-57
    Sponsor's Protocol Code Number:Penta21
    National Competent Authority:Spain - AEMPS
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2022-08-30
    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 number2020-001426-57
    A.3Full title of the trial
    A randomised non-inferiority trial with nested PK to assess DTG/3TC fixed dose formulations for the maintenance of virological suppression in children
    with HIV infection aged 2 to <15 years old
    Ensayo aleatorizado de no inferioridad con farmacocinética para la evaluación de combinaciones de dosis fijas de DTG/3TC para el mantenimiento de la supresión virológica en menores entre 2 y 15 años con VIH.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A study to compare whether giving two rather than three anti-HIV medicines daily to children and young people, aged between 2 and 15 years is as
    safe and effective in controlling their HIV infection
    Ensayo para comparar si la administración de dos en vez de tres fármacos anti-VIH diariamente en niños y pacientes jóvenes entre 2 y 15 años es tan segura y efectiva en el control de su infección por VIH.
    A.3.2Name or abbreviated title of the trial where available
    D3
    A.4.1Sponsor's protocol code numberPenta21
    A.5.1ISRCTN (International Standard Randomised Controlled Trial) NumberISRCTN17157458
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT04337450
    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 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 supportViiV Healthcare UK Limited
    B.4.2CountryUnited Kingdom
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationMRC CTU at UCL
    B.5.2Functional name of contact pointClinical Trials Information
    B.5.3 Address:
    B.5.3.1Street AddressMRC CTU at UCL, ICTM, 90 High Holborn
    B.5.3.2Town/ cityLondon
    B.5.3.3Post codeWC1V 6LJ
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number+44(0)20 7670 4810
    B.5.6E-mailmrcctu.d3trial@ucl.ac.uk
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameDTG/3TC DT
    D.3.2Product code Dolutegravir
    D.3.4Pharmaceutical form Dispersible tablet
    D.3.4.1Specific paediatric formulation Yes
    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 INNDolutegravir
    D.3.9.1CAS number 1051375-16-6
    D.3.9.3Other descriptive nameDolutegravir
    D.3.9.4EV Substance CodeSUB35122
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typerange
    D.3.10.3Concentration number15 to 30
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNLamivudine
    D.3.9.1CAS number 134678-17-4
    D.3.9.3Other descriptive nameLamivudine
    D.3.9.4EV Substance CodeSUB08392MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typerange
    D.3.10.3Concentration number90 to 180
    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 Dovato
    D.2.1.1.2Name of the Marketing Authorisation holderViiV Healthcare B.V.
    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 nameDovato
    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 INNDolutegravir
    D.3.9.1CAS number 1051375-16-6
    D.3.9.3Other descriptive nameDolutegravir
    D.3.9.4EV Substance CodeSUB35122
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number50
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNLamivudine
    D.3.9.1CAS number 134678-17-4
    D.3.9.3Other descriptive nameLamivudine
    D.3.9.4EV Substance CodeSUB08392MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number300
    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 Yes
    D.2.1.1.1Trade name TIVICAY PD
    D.2.1.1.2Name of the Marketing Authorisation holderViiV Healthcare B.V.
    D.2.1.2Country which granted the Marketing AuthorisationSpain
    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 nameTivicay PD
    D.3.4Pharmaceutical form Dispersible tablet
    D.3.4.1Specific paediatric formulation Yes
    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 INNDolutegravir
    D.3.9.1CAS number 1051375-16-6
    D.3.9.3Other descriptive nameDolutegravir
    D.3.9.4EV Substance CodeSUB35122
    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.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 TIVICAY
    D.2.1.1.2Name of the Marketing Authorisation holderViiV Healthcare B.V.
    D.2.1.2Country which granted the Marketing AuthorisationSpain
    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 nameTivicay
    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 INNDolutegravir
    D.3.9.1CAS number 1051375-16-6
    D.3.9.3Other descriptive nameDolutegravir
    D.3.9.4EV Substance CodeSUB35122
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    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 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 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 Triumeq
    D.2.1.1.2Name of the Marketing Authorisation holderViiV Healthcare UK Limited
    D.2.1.2Country which granted the Marketing AuthorisationSpain
    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 nameTriumeq
    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 INNLamivudine
    D.3.9.1CAS number 134678-17-4
    D.3.9.3Other descriptive nameLamivudine
    D.3.9.4EV Substance CodeSUB08392MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number50
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNAbacavir Sulfate
    D.3.9.1CAS number 188062-50-2
    D.3.9.3Other descriptive nameAbacavir sulfate
    D.3.9.4EV Substance CodeSUB00231MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number600
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNDolutegravir sodium
    D.3.9.1CAS number 1051375-19-9
    D.3.9.3Other descriptive nameDolutegravir sodium
    D.3.9.4EV Substance CodeSUB130591
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number300
    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 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 Kivexa
    D.2.1.1.2Name of the Marketing Authorisation holderViiV Healthcare B.V
    D.2.1.2Country which granted the Marketing AuthorisationSpain
    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 nameKivexa
    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 INNLamivudine
    D.3.9.1CAS number 134678-17-4
    D.3.9.3Other descriptive nameLamivudine
    D.3.9.4EV Substance CodeSUB08392MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number600
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNAbacavir sulfate
    D.3.9.1CAS number 188062-50-2
    D.3.9.3Other descriptive nameAbacavir sulfate
    D.3.9.4EV Substance CodeSUB00231MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number300
    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: 7
    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 Ziagen
    D.2.1.1.2Name of the Marketing Authorisation holderViiV Healthcare B.V.
    D.2.1.2Country which granted the Marketing AuthorisationSpain
    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 nameZiagen
    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 INNAbacavir sulfate
    D.3.9.1CAS number 188062-50-2
    D.3.9.3Other descriptive nameAbacavir sulfate
    D.3.9.4EV Substance CodeSUB00231MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number300
    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: 8
    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 Epivir
    D.2.1.1.2Name of the Marketing Authorisation holderViiV Healthcare B.V.
    D.2.1.2Country which granted the Marketing AuthorisationSpain
    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 nameEpivir
    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 INNLamivudine
    D.3.9.1CAS number 134678-17-4
    D.3.9.3Other descriptive nameLamivudine
    D.3.9.4EV Substance CodeSUB08392MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typerange
    D.3.10.3Concentration number150 to 300
    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: 9
    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 Combivir
    D.2.1.1.2Name of the Marketing Authorisation holderViiV Healthcare B.V
    D.2.1.2Country which granted the Marketing AuthorisationSpain
    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 nameCombivir
    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 INNLamivudine
    D.3.9.1CAS number 134678-17-4
    D.3.9.3Other descriptive nameLamivudine
    D.3.9.4EV Substance CodeSUB08392MIG
    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.IMP: 10
    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 Retrovir
    D.2.1.1.2Name of the Marketing Authorisation holderViiV Healthcare B.V.
    D.2.1.2Country which granted the Marketing AuthorisationSpain
    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 nameRetrovir
    D.3.4Pharmaceutical form Capsule, hard
    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 INNZidovudine
    D.3.9.1CAS number 30516-87-1
    D.3.9.3Other descriptive nameZidovudine
    D.3.9.4EV Substance CodeSUB00153MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typerange
    D.3.10.3Concentration number100 to 250
    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: 11
    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 Truvada
    D.2.1.1.2Name of the Marketing Authorisation holderGilead Sciences Ireland UC
    D.2.1.2Country which granted the Marketing AuthorisationSpain
    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 nameTruvada
    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 INNTenofovir disoproxil fumarate
    D.3.9.1CAS number 202138-50-9
    D.3.9.3Other descriptive nameTenofovir disoproxil fumarate
    D.3.9.4EV Substance CodeSUB12607MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number200
    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: 12
    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 Descovy
    D.2.1.1.2Name of the Marketing Authorisation holderGilead Sciences Ltd
    D.2.1.2Country which granted the Marketing AuthorisationSpain
    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 nameDescovy
    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 INNEmtricitabine
    D.3.9.1CAS number 143491-57-0
    D.3.9.3Other descriptive nameEmtricitabine
    D.3.9.4EV Substance CodeSUB01882MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number200
    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
    HIV Infection
    Infección por VIH
    E.1.1.1Medical condition in easily understood language
    HIV Infection
    Infección por VIH
    E.1.1.2Therapeutic area Diseases [C] - Virus Diseases [C02]
    MedDRA Classification
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    PRIMARY OBJECTIVE
    To assess whether DTG/3TC is non-inferior to DTG + 2 NRTIs in terms of virological suppression
    El brazo DTG/3TC tendrá una eficacia virológica no inferior comparado con DTG + 2 ITIAN
    E.2.2Secondary objectives of the trial
    SECONDARY OBJECTIVES
     To evaluate clinical and laboratory adverse events (AEs) associated with the trial antiretrovirals
     To evaluate new resistance mutations in participants with virological rebound (confirmed VL≥50 copies/mL)
     To assess low level viraemia and virological reservoirs
     To evaluate adherence, tolerability, acceptability, sleep and health-related quality of life
     To evaluate and model the pharmacokinetics and pharmacodynamics of dispersible and film-coated fixed-dose DTG/3TC formulations in children
    weighing 6-<40kg using WHO weight band-aligned dosing
     To evaluate cost-effectiveness of treatment maintenance with DTG/3TC FDC if DTG/3TC is shown to be non-inferior to DTG + 2 NRTIs
    OBJETIVOS SECUNDARIOS
     Evaluar los acontecimientos adversos clínicos y de laboratorio asociados con los antiretrovirales del estudio.
     Evaluar nuevas mutaciones asociadas a resistencia en participantes con VIH-1 ARN ≥50c/mL confirmado.
     Evaluar bajos niveles de viremia y reservorios víricos.
     Evaluar adherencia, tolerabilidad, aceptabilidad, calidad de sueño y calidad de vida con respecto a la salud.
     Evaluar y modelar las farmacocinéticas y farmacodinámicas de las formulaciones de dosis fija de DTG/3TC solubles y recubiertas con película en niños de entre 6 y menos de 40 kg utilizando la dosificación alineada con la banda de peso de la OMS.
    Evaluar el coste-efectividad del tratamiento de mantenimiento con DTG/3TC FDC si DTG/3TC demuestra no ser inferior a DTG + 2 NRTIs.
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    VIROLOGY SUBSTUDY
    ULTRASENSITIVE VIRAL LOAD TESTING AND HIV RESERVOIR
    Reduced ART may result in viral replicative activity below detection by routine viral load tests, which can contribute to increased viral reservoirs
    increased immune activation, inflammation and immune senescence.92,93
    AIM: to compare low level viraemia and viral reservoirs in DTG/3TC and control arms.
    Efficacy of DTG/3TC dual therapy will be further investigated by assessing its effect on very low level viraemia and the HIV reservoir. Total HIV-1 DNA
    will be used as a surrogate measure of HIV-1 reservoir size.91 Low level viraemia (quantitation limit 1-5 copies/mL depending on the available plasma
    volume) and total HIV-1 DNA will be assessed retrospectively on stored plasma and buffy coat respectively. Plasma will be collected at baseline and
    each study visit according to the trial assessment schedule. Blood samples for buffy coat storage will be collected at enrolment, 4, 12 and then every
    12 weeks using the same blood draw (Table 1). Samples will be stored locally and later transferred to the Advanced Pathogen Diagnostics Unit
    (APDU) at UCLH or the African Health Research Institute (AHRI) laboratory for analyses. The ultrasensitive quantitative HIV-1 RNA will be assessed
    by in house modified protocol using the HOLOGIC® APTIMA HIV-1QuantDx 94 and the HIV-1 DNA will be assessed by in-house quantitative PCR.95
    HEALTH ECONOMICS
    If dual therapy is shown to be safe and non-inferior to DTG-based triple ART in terms of virological efficacy it is likely that there will be substantial
    individual and societal cost savings associated with taking one less drug for the lifetime of an HIV-infected person.
    Aim: to compare net health benefits and incremental cost-effectiveness ratios (ICERs) of DTG/3TC dual therapy and DTG-based triple ART.
    Policy makers require information on the costs and health effects of alternative interventions to inform the allocation of limited health care resources to
    meet population’s health needs. In this study, we will estimate the costs and cost-effectiveness of DTG/3TC versus DTG-based triple ART to help
    inform policy makers on whether dual DTG/3TC represents a valuable use of health care resources. Outcomes will be evaluated using generic health
    measures (quality-adjusted life years (QALYs) and disability-adjusted life years (DALYs) averted) to allow for comparison with other interventions.
    Costs will be estimated from a health care perspective. For the cost-effectiveness analysis, the cost of the treatment interventions will be related to
    their health outcomes (QALYs, DALYs). Cost-effectiveness will be summarised using both net health benefits - the health gain resulting from one
    treatment compared to another less the health opportunity cost forgone elsewhere as a result of the resources not being available for others - and
    incremental cost-effectiveness ratios (ICERs) – the cost per DALY-averted or QALY gained associated with more effective, but more costly
    alternatives. Determining cost-effectiveness requires comparison of the treatments to other claims on limited resources, which are captured using
    cost-effectiveness thresholds. The trial will measure healthcare-related resource use in trial participants, starting at randomisation and continuing for
    the duration of follow-up. Information on ART received, concomitant medications, hospitalisations (number, reason, and duration of stay) and clinic
    visits will be recorded on eCRFs which will be collected at weeks 0, 4, 12 and then 12-weekly until the last participant reaches 96 weeks. Total costs
    will be estimated by applying appropriate unit costs and prices to resource use in trial participants. For unit costs / prices, two analyses will be
    conducted, one where a common set of unit costs / prices is used which is reflective of costs across LMIC and a second where country specific unit
    costs / prices are used.
    SUBESTUDIO DE VIROLOGÍA
    La reducción de la ART puede dar lugar a una actividad replicativa viral por debajo de la detección mediante las pruebas rutinarias de carga viral, lo que puede contribuir al aumento de los reservorios virales, a la activación inmunitaria, a la inflamación y a la senescencia inmunitaria.
    AIM: comparar el bajo nivel de viremia y los reservorios virales en los brazos de DTG/3TC y control.Se investigará la eficacia de la terapia dual DTG/3TC evaluando su efecto sobre los bajos niveles de viremia y el reservorio del VIH. El ADN total del VIH-1 se utilizará como medida sustitutiva del tamaño del reservorio del VIH-1. Los niveles bajos de viremia y el ADN total del VIH-1 se evaluarán retrospectivamente en el plasma almacenado y en la buffy coat, respectivamente. El plasma se recogerá al inicio y en cada visita del estudio de acuerdo con el cronograma de evaluación del ensayo. Las muestras de sangre para el almacenamiento de buffy coat se recogerán en el momento de la inclusión, a las 4 semanas, a las 12 semanas y luego cada 12 semanas utilizando la misma extracción de sangre. Las muestras se almacenarán localmente y posteriormente se trasladarán a la Unidad de Diagnóstico Avanzado de Patógenos del UCLH o al laboratorio del Instituto Africano de Investigación Sanitaria para su análisis. El ARN cuantitativo del VIH-1 se evaluará mediante un protocolo interno modificado y el ADN del VIH-1 se evaluará mediante una PCR cuantitativa interna.

    ECONOMÍA DE LA SALUD
    Si se demuestra que la terapia dual es segura y no es inferior a la triple terapia antirretroviral basada en DTG en términos de eficacia virológica, es probable que se produzca un importante ahorro de costes individuales y sociales asociado a la toma de un medicamento menos durante la vida de una persona infectada por el VIH.
    AIM: comparar los beneficios netos para la salud y las relaciones coste-eficacia incrementales de la terapia dual DTG/3TC y el triple TAR basado en DTG.
    En este estudio, estimaremos los costes y la rentabilidad de la DTG/3TC frente a la triple terapia antirretroviral basada en la DTG para ayudar a informar a los responsables políticos sobre si la DTG/3TC dual representa un uso valioso de los recursos sanitarios. Los resultados se evaluarán utilizando medidas de salud genéricas para permitir la comparación con otras intervenciones.
    Los costes se calcularán desde la perspectiva de la asistencia sanitaria. Para el análisis de rentabilidad, el coste de las intervenciones terapéuticas se relacionará con sus resultados sanitarios. La relación coste-eficacia se resumirá utilizando tanto los beneficios netos para la salud la ganancia de salud resultante de un tratamiento en comparación con otro menos el coste de oportunidad de salud que se deja de percibir en otro lugar como resultado de los recursos que no están disponibles para otros como las relaciones coste-eficacia incrementales el coste por AVAD o AVC ganado asociado a alternativas más eficaces, pero más costosas. La determinación de la rentabilidad requiere la comparación de los tratamientos con otras demandas de recursos limitados, que se captan mediante umbrales de rentabilidad. El ensayo medirá el uso de recursos relacionados con la atención sanitaria en los participantes del ensayo, comenzando en la aleatorización y continuando durante el seguimiento. La información sobre el tratamiento antirretroviral recibido, la medicación concomitante, las hospitalizaciones y las visitas a la clínica se registrarán en formularios electrónicos que se recogerán en las semanas 0, 4 y 12, y luego cada 12 semanas hasta que el último participante alcance las 96 semanas. Los costes totales se calcularán aplicando los costes unitarios y los precios adecuados al uso de los recursos en los participantes del ensayo. Para los costes/precios unitarios, se realizarán dos análisis


    E.3Principal inclusion criteria
    1. HIV-1 infected children who are virologically suppressed for at least the last 6 months prior to enrolmenta,b
    2. Aged 2 to <15 years old
    3. Weight 6 kg or higher
    4. Girls who have reached menarche must have a negative pregnancy test at screening and randomisation
    5. Girls who are sexually active must be willing to adhere to highly effective methods of contraceptionc
    6. A parent or legal guardian is willing and able to give informed consent on behalf of the child as per national legislation and willing to adhere to the
    protocol
    7. Participant is willing to give informed assent if the trial site clinician deems them old enough and able to understand the age-appropriate information
    about participation in the study
    PRINCIPALES CRITERIOS DE INCLUSIÓN
    1. Niños infectados por el VIH-1 con supresión virológica durante al menos los últimos 6 meses antes de la inclusión.
    2. De 2 a 15 años.
    3. Peso de 6 kg o más.
    4. Las niñas que han llegado a la menarquía deben tener una prueba de embarazo negativa en la selección y la aleatorización.
    5. Las niñas sexualmente activas deben estar dispuestas a cumplir métodos anticonceptivos altamente efectivos
    6. ElPadre, madre o tutor legal está dispuesto/a y es capaz de dar su consentimiento informado en nombre del niño/a según la legislación nacional y estará dispuesto a cumplir el protocolo.
    7. El participante está dispuesto a firmar el consentimiento informado si el investigador del ensayo lo considera lo suficientemente mayor y capaz de comprender la información.
    E.4Principal exclusion criteria
    1. Any previous switch in ART regimen for virological, immunological or clinical treatment failure
    2. Evidence of previous resistance to 3TC or INSTIa
    3. Any prior use of regimens consisting of single or dual NRTIs with the exception of a course of zidovudine for prevention of mother to child
    transmission
    4. Known allergy or contraindications to dolutegravir or lamivudine
    5. Diagnosis of tuberculosis and on anti-tuberculosis treatment; children can be enrolled after successful tuberculosis treatmentb
    6. Treatment of co-morbidities with drugs which have significant interactions with antiretroviral treatment, requiring dose adjustment of the study drugs
    (children can be enrolled after the illness resolves)
    7. Randomisation visit more than 12 weeks after the most recent screening visit
    8. Positive HBsAg c
    9. Screening ALT equal to 3 or more times the upper limit of normal AND bilirubin equal to 2 or more times the upper limit of normal (ALT ≥3xULN
    AND bilirubin ≥2xULN)
    10. Screening ALT equal to 5 or more times the upper limit of normal ALT (≥5xULN)
    11. Patients with severe hepatic impairment or unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy,
    hypoalbuminaemia, oesophageal or gastric varices, or persistent jaundice), or known biliary abnormalities (with the exception of Gilbert's syndrome or
    asymptomatic gallstones)
    12. Screening creatinine clearance <30 mL/min/1.73m2 d
    13. Patients aged ≥6 years at moderate or high risk of suicide as determined by Columbia-Suicide Severity Rating Scale (C-SSRS) e
    14. Girls who are pregnant or breastfeeding
    15. Children who are in the legal custody of the state and do not have a parent or guardian able to provide informed consent on their behalf
    PRINCIPALES CRITERIOS DE EXCLUSIÓN
    1. Cualquier cambio previo en el régimen de TAR por razones virológicas, inmunológicas o fracaso del tratamiento clínico.
    2. Evidencia de resistencia previa a 3TC o INSTI.
    3. Cualquier uso previo de regímenes consistentes en NRTI únicos o duales con la
    excepción de un curso de zidovudina para la prevención de la trasmisión de madre a hijo.
    4. Alergia o contraindicaciones conocidas a dolutegravir o lamivudina.
    5. Diagnóstico de tuberculosis y/o tratamiento antituberculoso; podrán incluirse pacientes que hayan recibido un tratamiento eficaz contra la tuberculosis.
    6. Tratamiento de comorbilidades con medicamentos que tienen interacciones con el tratamiento antirretroviral, requiriendo un ajuste de la dosis de los medicamentos del estudio (los pacientes pueden ser incluidos tras la resolución de la enfermedad).
    7. La visita de aleatorización se realiza más de 12 semanas después de la visita de screening más reciente.
    8. HBsAg positivo.
    9. El valor basal de ALT es igual o superior a 3 veces al límite superior de la normalidad Y el nivel de bilirrubina es igual o superior 2 veces al límite superior de la normalidad (ALT ≥3xLSN Y bilirrubina ≥2xLSN).
    10. El valor basal de ALT es igual o superior a 5 veces al límite superior de la normalidad ALT (ALT≥5xLSN)
    11. Pacientes con insuficiencia hepática grave o enfermedad hepática inestable (como
    definida por la presencia de ascitis, encefalopatía, coagulopatía, hipoalbuminemia, várices esofágicas o gástricas, o ictericia persistente), o anomalías biliares conocidas (con la excepción del síndrome de Gilbert o cálculos biliares asintomáticos).
    12. El nivel basal de aclaramiento de creatinina es <30 ml/min/1,73 m2.
    13. Pacientes ≥6 años con riesgo moderado o alto de suicidio determinado por la Escala de clasificación de la gravedad del suicidio de Columbia (C-SSRS).
    14. Pacientes embarazadas o en periodo de lactancia.
    15. Pacientes que están bajo la custodia legal del Estado y no tienen un padre o tutor capaz de dar el consentimiento informado en su nombre.
    E.5 End points
    E.5.1Primary end point(s)
    Proportion of children with confirmed viral rebound (defined as the first of two consecutive HIV-1 RNA ≥50c/mL) by week 96
    Medidas de resultado primarias

    Proporción de menores con un rebrote viral confirmado (definido como el primero de dos resultados consecutivos con VIH-1 ARN ≥50c/) antes de la semana 96.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Week 96
    Semana 96
    E.5.2Secondary end point(s)
    SECONDARY EFFICACY OUTCOME MEASURES
    1 Proportion of children with confirmed viral rebound (defined as the first of two consecutive HIV-1 RNA ≥50c/mL) by week 48.
    2 Proportion of children with confirmed HIV-1 RNA ≥50c/mL at weeks 48 and 96 (modified FDA snapshot)
    3 Proportion of children with HIV-1 RNA ≥50c/mL at weeks 24, 48 and 96 (including blips and confirmed measures ≥50c/mL)
    4 New resistance-associated mutations in those with confirmed HIV-1 RNA ≥50c/mL
    5 Time to any new or recurrent WHO 3 or WHO 4 event or death
    6 Change in CD4 (absolute and percentage) from baseline to weeks 24, 48 and 96
    SECONDARY SAFETY OUTCOME MEASURES
    1 Incidence of serious adverse events, grade ≥3 clinical and laboratory adverse events
    2 Incidence of adverse events leading to discontinuation or modification of the treatment regimen
    3 Proportion of children with a change in ART for toxicity or switch to second-line
    4 Change in blood lipids from baseline to weeks 48 and 96
    5 Change in creatinine clearance estimated using bedside-Schwartz to weeks 48 and 96
    PATIENT-REPORTED OUTCOME MEASURES
    1 Adherence as assessed by participant/care-giver questionnaires
    2 Acceptability, sleep and mood, suicidality ideation and health-related quality of life as assessed by participant/care-giver completed questionnaires
    Medidas de resultado secundarias

    •Proporción de menores con un rebrote viral confirmado (definido como el primero de dos resultados consecutivos con VIH-1 ARN ≥50c/mL) antes de la semana 48.

    •Proporción de menores con VIH-1 ARN ≥50c/mL confirmado en las semanas 48y96(análisis de snapshot FDA modificado).

    •Proporción de menores con VIH-1 ARN ≥50c/mL en las semanas 24, 48 y96 (incluyen “blips” y resultados ≥50c/mL confirmados).

    •Nuevas mutaciones asociadas a resistencia en participantes con VIH-1 ARN ≥50c/mL confirmado.

    •Periodo de tiempo transcurrido hasta un acontecimiento nuevo o recurrente de grado 3 o 4 OMS o defunción.

    •Desviaciones en el recuento CD4 (absoluto y en porcentaje) con respecto al valor base en las semanas 24, 48 y 96.

    Medidas de resultados de seguridad secundarias

    •Incidencia de acontecimientos adversos graves, acontecimientos clínicos y de laboratorio adversos de grado ≥ 3.

    •Incidencia de acontecimientos adversos graves que resultan en interrupción o modificación del régimen de tratamiento

    •Proporción de menores con cambios en el TAR debido a toxicidad o transferencia a TAR de segunda línea.

    •Cambio en los lípidos en sangre con respecto al valor base en las semanas 48 y 96.

    •Cambio en la depuración de creatinina estimada con la fórmula Bedside-Schwartz en las semanas 48 y 96.

    Medidas de resultados percibidos por los pacientes

    •Adherencia evaluada según los cuestionarios completados por participante/cuidador.
    •Aceptabilidad, calidad de sueño y estado de ánimo, pensamientos suicidas y calidad de vida con respecto a la salud evaluados según los cuestionarios completados por el paciente/cuidador.
    E.5.2.1Timepoint(s) of evaluation of this end point
    SECONDARY EFFICACY OUTCOME MEASURES
    1 Week 48.
    2 Weeks 48 and 96
    3 Weeks 24, 48 and 96
    4 Week 96
    5 End of trial visit
    6 Weeks 24, 48 and 96
    SECONDARY SAFETY OUTCOME MEASURES
    1 End of trial visit
    2 End of trial visit
    3 End of trial visit
    4 Weeks 48 and 96
    5 Weeks 48 and 96
    PATIENT-REPORTED OUTCOME MEASURES
    1 Week 0, Week 4, Week 12, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84, Week 96
    2 Acceptability, Sleep and Mood, Health Related Quality of Life : Week 0, Week 4, Week 24, Week 48, Week 72, Week 96
    2 Suicidality: Week 0, Week 4, Week 12, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84, Week 96
    1.Medidas de resultados de eficacia secundarias
    Semana 48
    Semanas 48 and 96
    Semanas 24, 48 and 96
    Semana 96
    Visita de fin de tratamiento
    Semanas 24, 48 and 96

    2.Medidas de resultados de seguridad secundarias
    Visita de fin de tratamiento
    Visita de fin de tratamiento
    Visita de fin de tratamiento
    Semanas 48 and 96
    Semanas 48 and 96

    3.Medidas de resultados percibidos por los pacientes
    Semana 0
    Semana 4
    Semana 12
    Semana 24
    Semana 36
    Semana 48
    Semana 60
    Semana 72
    Semana 84
    Semana 96

    Aceptabilidad, calidad de sueño y estado de ánimo y calidad de vida con respecto a la salud: Semana 0, Semana 4, Semana 24, Semana 48, Semana 72, Semana 96

    Suicidio: Semana 0, Semana 4, Semana 12, Semana 24, Semana 36, Semana 48, Semana 60, Semana 72, Semana 84, Semana 96
    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 No
    E.6.10Pharmacogenetic Yes
    E.6.11Pharmacogenomic Yes
    E.6.12Pharmacoeconomic Yes
    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 Yes
    E.8.1.7.1Other trial design description
    Non-inferiority trial
    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 concerned2
    E.8.5The trial involves multiple Member States No
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA 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
    South Africa
    Thailand
    Uganda
    Spain
    United Kingdom
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    The end of trial will be when all participants have completed follow-up, including extra visits for viral load, all data have been obtained and the database has been locked.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years3
    E.8.9.1In the Member State concerned months
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years3
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 Yes
    F.1.1Number of subjects for this age range: 6
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) Yes
    F.1.1.5.1Number of subjects for this age range: 1
    F.1.1.6Adolescents (12-17 years) Yes
    F.1.1.6.1Number of subjects for this age range: 3
    F.1.2Adults (18-64 years) No
    F.1.3Elderly (>=65 years) No
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception 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 as they are below the age of consent will give assent to the trial, where they are deemed old enough and mature enough to understand the
    trial information. Parents/caregivers will consent to their child participating in the trial.
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state10
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 10
    F.4.2.2In the whole clinical trial 370
    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)
    The contract with supporting pharmaceutical companies will specify that the supply of study drugs is limited to the duration of the trial in each
    individual participant, however, the provision of DTG/3TC to participants randomised to the formulation may be extended in particular circumstances.
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2023-04-25
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2023-04-03
    P. End of Trial
    P.End of Trial StatusOngoing
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