Clinical Trials Register

Summary
EudraCT Number:	2014-002632-14
Sponsor's Protocol Code Number:	ODYSSEY(PENTA20)
National Competent Authority:	Portugal - INFARMED
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2017-03-24
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

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A. Protocol Information

A.1

Member State Concerned

Portugal - INFARMED

A.2

EudraCT number

2014-002632-14

A.3

Full title of the trial

A randomised trial of dolutegravir (DTG)-based antiretroviral therapy vs. standard of care (SOC) in children with HIV infection starting first-line or switching to second-line ART.

Ensaio randomizado de terapêutica antirretrovírica (TARV) baseada em dolutegravir (DTG) em comparação com o tratamento padrão (SOC) em crianças infectadas pelo VIH a iniciar primeira linha de TARV ou a mudar para segunda linha de TARV.

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A randomised trial of dolutegravir (DTG)-based antiretroviral treatment vs standard of care (SOC) in children with HIV infection starting first treatment or switching to second-line antiretrovirals.

Ensaio randomizado de terapêutica antirretrovírica baseada em dolutegravir (DTG) em comparação com o tratamento padrão (SOC) em crianças infectadas pelo VIH a iniciar primeira linha de terapêutica antirretrovírica ou a mudar para segunda linha de terapêutica antirretrovírica.

A.3.2

Name or abbreviated title of the trial where available

ODYSSEY (Once daily DTG-based ART in young people vs standard therapy)

A.4.1

Sponsor's protocol code number

ODYSSEY(PENTA20)

A.5.1

ISRCTN (International Standard Randomised Controlled Trial) Number

ISRCTN91737921

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT02259127

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Fondazione PENTA ONLUS
B.1.3.4	Country	Italy
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Viiv Healthcare Ltd
B.4.2	Country	United Kingdom
B.4.1	Name of organisation providing support	Fondazione PENTA ONLUS
B.4.2	Country	Italy
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Inserm SC10-US19
B.5.2	Functional name of contact point	Alexandra COMPAGNUCCI
B.5.3	Address:
B.5.3.1	Street Address	16 Avenue Paul Vaillant Couturier
B.5.3.2	Town/ city	Villejuif
B.5.3.3	Post code	94807
B.5.3.4	Country	France
B.5.4	Telephone number	0033145595290
B.5.5	Fax number	0033146587293
B.5.6	E-mail	arc-penta.sc10@inserm.fr

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Tivicay 50mg film-coated tablets
D.2.1.1.2	Name of the Marketing Authorisation holder	Viiv Healthcare UK Limited
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Tivicay (dolutegravir) 50mg
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Dolutegravir (as sodium)
D.3.9.1	CAS number	1051375-19-9
D.3.9.2	Current sponsor code	GSK1349572
D.3.9.4	EV Substance Code	AS1
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	50
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Tivicay 25mg film-coated tablets
D.2.1.1.2	Name of the Marketing Authorisation holder	ViiV Healthcare UK Limited
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Dolutegravir 25mg
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	Yes
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Dolutegravir (as sodium)
D.3.9.1	CAS number	1051375-19-9
D.3.9.2	Current sponsor code	GSK1349572
D.3.9.4	EV Substance Code	AS5
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	25
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 3
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Tivicay 10 mg film-coated tablets
D.2.1.1.2	Name of the Marketing Authorisation holder	ViiV Healthcare UK Limited
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Dolutegravir 10mg
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	Yes
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Dolutegravir (as sodium)
D.3.9.1	CAS number	1051375-19-9
D.3.9.2	Current sponsor code	GSK1349572
D.3.9.4	EV Substance Code	AS7
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 4
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Triumeq 50mg/600mg/300mg film-coated tablets
D.2.1.1.2	Name of the Marketing Authorisation holder	ViiV Healthcare UK Limited
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Triumeq 50mg/600mg/300mg
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Dolutegravir (as sodium)
D.3.9.1	CAS number	1051375-19-9
D.3.9.2	Current sponsor code	GSK1349572
D.3.9.4	EV Substance Code	AS2
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	50
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Abacavir (as sulphate)
D.3.9.1	CAS number	188062-50-2
D.3.9.4	EV Substance Code	AS3
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	600
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Lamivudine
D.3.9.1	CAS number	134678-17-4
D.3.9.4	EV Substance Code	AS4
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	300
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another 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.1.1

Medical condition(s) being investigated

Paediatric HIV infection

Infecção pelo HIV-1 em participantes pediátricos

E.1.1.1

Medical condition in easily understood language

Paediatric HIV infection

Infecção pelo HIV-1 em participantes pediátricos

E.1.1.2

Therapeutic area

Diseases [C] - Virus Diseases [C02]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10020161
E.1.2	Term	HIV infection
E.1.2	System Organ Class	10021881 - Infections and infestations

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To evaluate whether treatment with DTG works as well as the standard anti-HIV treatment in children.

Para avaliar se o tratamento com DTG funciona tão bem como o padrão de tratamento antiretrovírico em crianças.

E.2.2

Secondary objectives of the trial

To evaluate if treatment with DTG is better in terms of safety than standard anti-HIV treatment in children.

To compare the adherence to treatment and the quality of life of children receiving DTG to those receiving standard anti-HIV treatment.

Para avaliar se o tratamento com DTG é melhor em termos de segurança do que o tratamento antiretrovírico padrão em crianças.

Para comparar a adesão ao tratamento ea qualidade de vida de crianças que recebem DTG com aqueles que receberam o tratamento antiretrovírico padrão.

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

Pharmacokinetic substudy in participants developing TB while on DTG: To confirm DTG dosing in children receiving concomitant rifampicin for the treatment of TB. This substudy will be carried out in regions where TB is prevalent (ie not in Portugal).

Weight band PK substudies WB-PK1 and WB-PK2 will be undertaken in children 14 to < 40 kg with the aims of simplifying doses and formulations of DTG using WHO weight bands (ie not in Portugal).

Immunology/virology substudy: To compare mechanisms of CD4 reconstitution, immune activation and HIV reservoir and replication in DTG vs SOC arms.

Qualitative substudy will investigate how best to support children and young people to maintain optimal adherence to second-line treatment (ie not in Portugal).

The Youth Trial Board will develop a model of meaningful engagement and participation of adolescent patient representatives in paediatric clinical trials (ie not in Portugal).

Farmacocinética (PK) em participantes do estudo que contraiam TB durante a terapêutica com DTG: Para confirmar DTG dosagem em crianças que receberam a rifampicina concomitante para o tratamento de TB. Este sub-estudo será realizado em regiões onde a TB é predominante (ou seja, não em Portugal).

Os sub-estudos PK WB-PK1 e WB-PK2 serão realizados em crianças de 14 a <40 kg com o objectivo de simplificar as doses e formulações de DTG utilizando bandas de peso da OMS (ou seja, não em Portugal).

Subestudo de imunologia/virologia
Serão comparados os mecanismos de reconstituição de CD4, ativação imunológica, reservatórios de VIH e replicação do vírus nos grupos DTG e SOC.

Subestudo qualitativo irá investigar a melhor forma de apoiar as crianças e os jovens a manter a adesão óptima ao tratamento de segunda linha (ou seja, não em Portugal).

O Julgamento juvenil Conselho irá desenvolver um modelo de envolvimento significativo e participação de representantes de pacientes adolescentes em ensaios clínicos pediátricos (ou seja, não em Portugal).

E.3

Principal inclusion criteria

Children <18 years weighing ¿14kg with confirmed HIV-1 infection and DTG dose known for child's weight-band*
Parents/carers and children, where applicable, give informed written consent
Girls who have reached menses must have a negative pregnancy test at screening and randomisation and be willing to adhere to effective methods of contraception if sexually active
Children with co-infections who need to start ART according to local/national guidelines
Parents/carers and children, where applicable, willing to adhere to a minimum of 96 weeks' follow-up

*Children weighing 14 to <20kg must be eligible and willing to participate in the Weight band (WB)-PK1 substudy unless enrolment for this weight band directly into the main trial has opened following the WB-PK1 substudy or dosing information has become available from the IMPAACT P1093 DTG dose-finding study.

Additional criteria for ODYSSEY A:
Planning to start first-line ART

Additional criteria for ODYSSEY B:
Planning to start second-line ART defined as either: (i) switch of at least 2 ART drugs due to treatment failure; or (ii) switch of only the third agent due to treatment failure where drug sensitivity tests show no mutations conferring NRTI resistance
Treated with only one previous ART regimen. Single drug substitutions for toxicity, or simplification, changes in national guidelines or drug availability are allowed.
At least one NRTI with predicted preserved activity available for a background regimen
In settings where resistance tests are routinely available, at least one active NRTI from tenofovir, abacavir or zidovudine should have preserved activity based on cumulative results of resistance tests
In settings where resistance tests are not routinely available, children who are due to switch according to national guidelines should have at least one new NRTI available from tenofovir, abacavir or zidovudine
Viral load ¿500 c/ml at screening visit or within 4 weeks prior to screening

TODOS OS PACIENTES:
¿Menores de 18 anos pesando ¿14kg com infecção pelo HIV-1 confirmada e dose de DTG já estabelecida para a faixa de peso da criança*
¿Assinatura de termo de consentimento livre e esclarecido pelos pais/responsáveis e pela criança, conforme aplicável
¿Meninas após a menarca precisam apresentar teste de gravidez negativo no momento da triagem e no momento da randomização; e, caso sexualmente ativas, precisam concordar em aderir ao uso de métodos eficazes de contracepção
¿Crianças com coinfecção que precisem iniciar TARV conforme as diretrizes locais/nacionais
¿Os pais/responsáveis e as crianças, conforme aplicável, devem estar dispostos a aderir a, no mínimo, 96 semanas de seguimento

*As crianças com peso entre 14 e <20kg devem ser elegíveis e dispostas a participar no subestudo da banda de peso (WB) -PK1, a não ser que a inscrição para esta banda de peso diretamente no ensaio principal tenha aberto após o subestudo WB-PK1 IMPAACT P1093 DTG estudo de pesquisa de dose.

CRITÉRIOS ADICIONAIS PARA ODYSSEY A:
¿Planejando iniciar primeira linha de TARV

CRITÉRIOS ADICIONAIS PARA ODYSSEY B:
¿Planejando iniciar segunda linha de TARV, definida como mudança de pelo menos 2 agentes de TAR devido a falha do tratamento; Ou (ii) mudança de apenas o terceiro agente devido a falha do tratamento quando os testes de sensibilidade aos fármacos não mostram mutações que conferem resistência a ITRN.
¿Tratamento prévio com apenas um regime de TARV. Permite-se substituição de apenas um fármaco por motivo de toxicidade, simplificação ou mudanças nas diretrizes nacionais ou disponibilidade de fármacos do regime.
¿Há pelo menos um ITRN com atividade preservada disponível para regime basal
¿Em locais onde há disponibilidade de exames de resistência como rotina, pelo menos um ITRN ativo, seja TDF, ABC ou ZDV, deve apresentar atividade preservada, com base nos resultados cumulativos de exames de resistência realizados
¿Em locais onde não há disponibilidade de exames de resistência como rotina, deve haver pelo menos um novo ITRN com previsão de atividade, seja TDF, ABC ou ZDV, disponível para as crianças que serão submetidas a troca de regime de acordo com as diretrizes nacionais
¿Carga viral ¿ 500 c / ml na visita de triagem ou dentro de 4 semanas antes da visita de triagem.

E.4

Principal exclusion criteria

History or presence of known allergy or contraindications to DTG.
History or presence of known allergy or contraindications to proposed available NRTI backbone or proposed available SOC third agent.
Alanine aminotransferase (ALT) ¿5 times the upper limit of normal (ULN), OR ALT ¿3xULN and bilirubin ¿2xULN.
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), known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
Anticipated need for Hepatitis C virus (HCV) therapy during the study.
Pregnancy or breastfeeding.
Evidence of lack of susceptibility to integrase inhibitors or more than a 2-week exposure to antiretrovirals of this class .

CRITÉRIOS PARA EXCLUSÃO DE PACIENTES
¿Histórico ou presença de alergia ou contra-indicações ao DTG.
¿Histórico ou presença de alergia conhecida ou contra-indicações ao esqueleto de ITRN disponível proposto ou ao terceiro agente SOC disponível proposto.
¿Alanina aminotransferase (ALT) ¿5 vezes o limite superior da normalidade (LSN) OU ALT ¿3x LSN e bilirrubina ¿2x LSN
¿Pacientes com comprometimento grave da função hepática ou doença hepática instável (definida pela presença de ascite, encefalopatia, coagulopatia, hipoalbuminemia, varizes esofágicas ou gástricas ou icterícia persistente), alterações biliares conhecidas (exceto síndrome de Gilbert ou cálculos biliares assintomáticos)
¿Expectativa de precisar de tratamento contra o vírus da hepatite C (HCV) durante o estudo
¿Gravidez ou lactação
¿Indícios de ausência de suscetibilidade aos inibidores da integrase ou mais de 2 semanas de exposição prévia a antirretrovirais desta classe.

E.5 End points

E.5.1

Primary end point(s)

Difference in the probability of virological or clinical failure by 96 weeks, estimated by Kaplan-Meier methods, using time to the first occurrence of any of the following components:
Insufficient virological response defined as <1 log10 drop at week 24
Viral load ¿400 c/ml at or after 36 weeks confirmed by next visit
Death due to any cause
Any new or recurrent AIDS defining event (WHO 4) or severe WHO 3 events, confirmed by the Endpoint Review Committee

Diferença na proporção de falência do tratamento (clínica ou virológica) em 96 semanas, estimada usando-se o tempo decorrido até a primeira ocorrência de qualquer um dos seguintes componentes:
¿Resposta virológica insuficiente, definida como redução <1 log10 na 24ª semana
¿Carga vírica (CV)¿400 cópias/mL na 36ª semana ou após (confirmada na visita seguinte)
¿Morte por qualquer causa
¿Qualquer evento definidor de SIDA (OMS 4), novo ou recorrente, ou evento grave (OMS 3), conforme adjudicação pelo Comité de Revisão de Resultados

E.5.1.1

Timepoint(s) of evaluation of this end point

96 weeks

96 semanas

E.5.2

Secondary end point(s)

Secondary efficacy outcomes:
Difference in proportion with clinical or virological failure (as defined above) by 48 weeks.
Time to any new or recurrent AIDS defining event (WHO 4) or severe WHO 3 events, confirmed by the Endpoint Review Committee
Proportion of children with VL <50 c/ml at 48 and 96 weeks
Proportion of children with VL <400 c/ml at 48 and 96 weeks
Rate of clinical events over 96 weeks: WHO 4, severe WHO 3 events and death
Change in CD4 count and CD4 percentage and CD4/CD8 ratio from baseline to weeks 48 and 96
Proportion developing new resistance mutations

Secondary safety outcomes:
Change in total cholesterol, triglycerides and lipid fractions (LDL, HDL) from baseline to weeks 48 and 96. Change in total cholesterol from baseline to week 96 will be used to formally assess superiority of DTG based regimen vs. SOC
Incidence of serious adverse events
Incidence of new clinical and laboratory grade 3 and 4 adverse events
Incidence of adverse events (of any grade) leading to treatment modification

Other secondary outcomes:
Quality of life
Adherence and acceptability

Resultados secundários de eficácia:
¿Diferença na proporção de falência clínica ou virológica (conforme definida acima) em 48 semanas
¿Tempo até a ocorrência de qualquer evento definidor de SIDA (OMS 4), novo ou recorrente, ou evento grave (OMS 3), conforme ao Comité de Revisão de Resultados, após 24 semanas da randomização
¿Proporção de crianças com supressão da carga vírica a <50 cópias/mL em 48 e 96 semanas
¿Proporção de crianças com supressão da carga vírica a <400 cópias/ml em 48 e 96 semanas
¿Proporção de eventos clínicos ao longo de 96 semanas: eventos OMS 4, eventos OMS 3 graves e morte
¿Alteração na contagem de CD4 e percentagem de CD4 e CD4 / CD8 desde a linha de base até as semanas 48 e 96
¿Proporção de participantes do estudo com desenvolvimento de novas mutações de resistência

Resultados secundários de segurança:
¿Alteração no colesterol total, frações (LDL, HDL) e triglicerídeos em relação ao valor basal nas semanas 48 e 96. Alteração do colesterol total desde a linha de base até a semana 96 será utilizada para avaliação formal do grupo DTG em comparação com o grupo SOC.
¿Incidência de eventos adversos sérios
¿Incidência de eventos adversos clínicos e laboratoriais de graus 3 e 4
¿Incidência de eventos adversos (de qualquer grau) necessitando modificação do tratamento

Outros resultados secundários:
¿Qualidade de vida
¿Adesão e aceitabilidade

E.5.2.1

Timepoint(s) of evaluation of this end point

48 weeks and 96 weeks

Entre 48 semanas e 96 semanas

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

Braço SOC: TARV com NNRTI/bPI/RAL + 2/3NRTIs escolhidos pelo o médico conforma as recomendações

SOC ARM: ART using either NNRTI/bPI/RAL + 2/3NRTIs at clinician choice following relevant guidelines

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Argentina

Brazil

France

Germany

Portugal

South Africa

Spain

Thailand

Uganda

United Kingdom

United States

Zimbabwe

E.8.7

Trial 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 trial will be considered closed when the last patient to be enrolled reaches 96 weeks of follow-up and exits the trial (for all other patients the exit visit will be their scheduled visit immediately prior to this), all data has been entered in the database, and queries have been resolved.

O ensaio será considerado encerrado quando o último paciente a ser incluído atinge 96 semanas de seguimento e sai do ensaio (para todos os outros pacientes a visita de saída será a sua visita agendada imediatamente anterior a este), todos os dados foram inseridos no banco de dados e consultas foram resolvidos

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

F.1.1