Clinical Trials Register

Summary
EudraCT Number:	2013-001476-37
Sponsor's Protocol Code Number:	PENTA17
National Competent Authority:	Portugal - INFARMED
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2015-12-11
Trial results	View 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

2013-001476-37

A.3

Full title of the trial

SMILE: Strategy for Maintenance of HIV suppression with once daiLy Integrase inhibitor+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 once daily integrase inhibitor administered with darunavir/ritonavir (DRV/r) in HIV-1 infected, virologically suppressed paediatric participants.

SMILE: Estratégia para manutenção da supressão do HIV com um inibidor da integrase uma vez por dia +darunavir/ritonavir em crianças (PENTA 17)
Um estudo randomizado, aberto, de fase 2/3 multicêntrico de dois grupos para avaliação da segurança e efeito antiviral da terapêutica antiretroviral padrão atual em comparação com um inibidor da integrase uma vez por dia administrado com darunavir/ritonavir (DRV/r) em participantes pediátricos com supressão viral infectados com HIV-1.

A.3.1

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

SMILE: Strategy for Maintenance of HIV suppression with once daiLy Integrase inhibitor+darunavir/ritonavir in childrEn (PENTA 17).

SMILE: Estratégia para manutenção da supressão do HIV com um inibidor da integrase uma vez por dia + darunavir/ritonavir em crianças (PENTA 17).

A.3.2

Name or abbreviated title of the trial where available

PENTA 17 - SMILE

A.4.1

Sponsor's protocol code number

PENTA17

A.5.1

ISRCTN (International Standard Randomised Controlled Trial) Number

ISRCTN11193709

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT02383108

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	Fondazione PENTA ONLUS
B.4.2	Country	Italy
B.4.1	Name of organisation providing support	Gilead Sciences International
B.4.2	Country	United States
B.4.1	Name of organisation providing support	Janssen-Cilag International NV
B.4.2	Country	Belgium
B.4.1	Name of organisation providing support	ViiV Healthcare Ltd
B.4.2	Country	United Kingdom
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	0033145 59 52 90
B.5.5	Fax number	0033146 58 72 93
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	Norvir
D.2.1.1.2	Name of the Marketing Authorisation holder	AbbVie Ltd
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	ritonavir
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	ritonavir
D.3.9.1	CAS number	155213-67-5
D.3.9.4	EV Substance Code	SUB10342MIG
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	100
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	Prezista
D.2.1.1.2	Name of the Marketing Authorisation holder	Janssen-Cilag International NV
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	darunavir
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	darunavir
D.3.9.1	CAS number	206361-99-1
D.3.9.4	EV Substance Code	SUB25394
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.3.11 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	Prezista
D.2.1.1.2	Name of the Marketing Authorisation holder	Janssen-Cilag International NV
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	darunavir
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	darunavir
D.3.9.1	CAS number	206361-99-1
D.3.9.4	EV Substance Code	SUB25394
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	75
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	Prezista
D.2.1.1.2	Name of the Marketing Authorisation holder	Janssen-Cilag International NV
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	darunavir
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	darunavir
D.3.9.1	CAS number	206361-99-1
D.3.9.4	EV Substance Code	SUB25394
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	800
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: 5
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	No
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	elvitegravir
D.3.2	Product code	GS-9137
D.3.4	Pharmaceutical form	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	elvitegravir
D.3.9.1	CAS number	697761-98-1
D.3.9.4	EV Substance Code	SUB69759
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	150
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: 6
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
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
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.3.9.3	Other descriptive name	dolutegravir sodium
D.3.9.4	EV Substance Code	SUB130591
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.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-1 Infection

Infecção pelo HIV-1 em participantes pediátricos

E.1.1.1

Medical condition in easily understood language

Paediatric HIV-1 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	20.1
E.1.2	Level	LLT
E.1.2	Classification code	10068341
E.1.2	Term	HIV-1 infection
E.1.2	System Organ Class	100000004862

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 children with chronic HIV infection on ART with suppressed viral load will maintain similar levels of suppression with once daily integrase inhibitor+ darunavir/r (INSTI+DRV/r) compared to current standard of care triple ART.

Para avaliar se crianças, infectadas pelo VIH-1 com supressão vírica e com regime de TAR triplo atual, manterão níveis de supressão semelhantes com um inibidor da integrase um vez por dia+darunavir/r (ITI+DRV/r) em comparação com a terapêutica tripla habitual.

E.2.2

Secondary objectives of the trial

- 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 INSTI+DRV/r compared to current standard of care triple ART.
- To evaluate INSTI+DRV/r drug exposure and drug-drug interactions.

- Para avaliar o efeito sobre a progressão clínica, os parâmetros imunológicos, a toxicidade mitocondrial, o perfil dos lipídios, a densidade mineral óssea, a adesão, a aceitação e a qualidade de vida com a combinação ITI+DRV/r em comparação com o regime TAR triplo atual standard.
- Para avaliar a exposição com ITI + DRV / r e as interações medicamentosas

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

1) Mitochondrial substudy
Objectives: To demonstrate differences in markers of mitochondrial toxicity between arms
2) 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.
3) 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 INSTI administered with DRV/r compared to standard NNRTI or PI-based 3-drug ART in HIV infected children maintain similar level of viral load.
4) DRV/r + INSTI sparse sampling and modeling
Objectives: To determine the pharmacokinetics of darunavir (DRV), ritonavir (RTV) and INSTI

1) Subestudo de toxicidade mitocondrial
Objectivos: Caracterizar os perfis de expressão de marcadores específicos de toxicidade mitocondrial entre os dois grupos.
2) Subestudo Lipídios/Densidade mineral óssea (DMO)
Objectivos: Documentar o desenvolvimento e a progressão de síndrome de lipodistrofia em um subgroupo de crianças.
Avaliar o efeito de uma simplificação de TAR sobre as modificações de DMO em crianças infectadas pelo HIV-1.
3) Virology
Objectivos: Os testes siguentes de laboratorio (resistencia, plasma HIV-1, RNA niveis ou carga virica) serão realizadas localmente com o objectivo de estudar se o regime ITI administrado com DRV/r em comparação com a terapêutica tripla habitual, em crianças infectadas pelo HIV-1 manterão níveis de carga virica semelhantes.
4) DRV/r + ITI amostragem e modelagem (farmacocinetica)
Objectivos: Determinar os parâmetros farmacocinéticos de darunavir (DRV), ritonavir (RTV) e INI

E.3

Principal inclusion criteria

1.HIV-1 infected children aged ≥12 years old and weighting ≥ 40kg* 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 24 weeks.
6.Children/parents/guardians prepared to switch if randomised to INSTI + darunavir/ritonavir arm
7.Children and parents prepared to restart the current ART regimen after simplification if viral load restart criteria are met
8.Be affiliated or beneficiary to Health Social security scheme (in countries where this is mandatory)

*. Initially, enrolment will be of participants ≥ 12 years old and ≥40kg only.
**. As more data become available on younger children, a protocol amendment is planned to include younger children and/or lower weight bands.

1.Crianças infectadas pelo HIV-1 com idades ≥ 12 anos e com peso ≥ 40kg* na visita de screening
2. Idades entre 6 a < 18 anos**
3.Pais ou responsáveis pela educação, e crianças, quando adequado, dispostos e com capacidade para darem o consentimento informado e a cumprirem o protocolo
4.As crianças devem ter a carga viral de RNA HIV-1 <50c/mL durante um mínimo de 12 meses com pelo menos dois resultados separados antes da observação.
5.As crianças sujeitas a PI/r com 3 fármacos ou NNRTI com um regime durante pelo menos 24 semanas.
6.Crianças/Pais/Responsável legal preparados para mudar se aleatorizados para o grupo de ITI + darunavir/ritonavir
7.Crianças e pais preparados para reiniciar o regime ART atual após simplificação se os critérios de reinício da carga viral forem cumpridos
8. Ser afiliado ou beneficiário ao regime de Segurança Social da Saúde (nos países onde é obrigatório)

*. Inicialmente, os participantes ≥ 12 anos e ≥40kg serão incluídos apenas.
**. À medida que mais dados estiverem disponíveis em crianças mais novas, uma adenda de protocolo é planejada para incluir crianças mais jovens e / ou faixas de menor peso.

E.4

Principal exclusion criteria

1.Receiving or requiring agents with interactions with DRV, RTV, or any once daily integrase inhibitor
2.Evidence of resistance to DRV or integrase inhibitors
3.Previous exposure to integrase inhibitors for more than 2 weeks
4.Intercurrent illness
5.Creatinine ≥ 1.8ULN or ALT ≥ 5ULN or ALT ≥ 3ULN and bilirubin ≥2ULN at screening.
6.Patients with severe hepatic impairment or unstable liver disease known biliary abnormalities
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
10. History or presence of known allergy or some other contraindication to the study drugs or their components as described in the SmPC

1.Que recebem ou necessitam de medicações que interagem com DRV, RTV ou um inibidor da integrase
2.Evidências de resistência ao DRV ou inibidores da integrase
3.Exposição prévia a inibidores da integrase durante mais de 2 semanas
4.Doença intercorrente
5. Creatinina ≥1.8ULN ou ALT ≥5ULN ou ALT ≥ 3ULN e bilirubina ≥2ULN no momento da observação.
6.Pacientes com insuficiência hepática grave ou doença hepática instável conhecidas anormalidades biliares
7. Diagnóstico de tuberculose e tratamento anti-tuberculose
8.Co-infecção com Hepatite B ou Hepatite C
9.Gravidez ou risco de gravidez em meninas em idade fértil a menos que assumam o compromisso de usarem contraceptivos eficazes
10. História ou presença de alergia conhecida ou alguma outra contra-indicação aos fármacos do estudo ou seus componentes conforme descrito no RCM

E.5 End points

E.5.1

Primary end point(s)

Percentage of patients with HIV-1 RNA ≥ 50 c/mL (confirmed within 4 weeks)

Percentagem de doentes com RNA VIH-1 que alguma vez tiveram ≥ 50 c/mL (confirmado no prazo de 4 semanas)

E.5.1.1

Timepoint(s) of evaluation of this end point

Any time up to week 48

em qualquer momento até à semana 48

E.5.2

Secondary end point(s)

•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
•Percentage of patients with any grade 3 or 4 clinical adverse events (particularly lipodystrophy); any grade 3 or 4 laboratory adverse events
•Any adverse event leading to discontinuation or modification of the treatment regimen
•Occurrence of resistance mutations defined by the current IAS-USA list
•Changes in CD4 (absolute and percentage) from baseline to weeks 24 and 48
•Change in ART (defined as any change from the ART regimen at randomisation)
•New or recurrent CDC stage C or severe stage B event or death
•Changes 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 older than 8 years)
•Date of first menses

•Percentagem de doentes com VIH-1 RNA ≥ 50 c/mL na semana 24 e na semana 48
•Percentagem de doentes com VIH-1 RNA ≥ 400c/mL na semana 24 e na semana 48
•Percentagem de doentes com quaiquer efeitos adversos clínicos de grau 3 ou 4 (especialmente lipodistrofia), quaiquer efeitos adversos laboratoriais de grau 3 ou 4
•Qualquer evento adverso que leve à interrupção ou modificação do regime de tratamento
•Ocorrência das mutações de resistência definidas pela lista da IAS-USA atual
•Alterações nos CD4 (absolutas e percentuais) desde o nível basal até às semanas 24 e 48
•Alteração no TAR (definida como qualquer alteração do regime TAR na altura da randomização)
•Evento novo ou recorrente de estádio C ou B grave do CDC ou morte
•Alteração de lipídos desde o nível basal até às semanas 24 e 48
•Adesão conforme avaliado por questionário e escala visual analógica
•Aceitabilidade e qualidade de vida durante 48 semanas conforme avaliado por questionários preenchidos pelos doentes
•Altura e peso
•Escalas de Tanner (em participantes com idade superior a 8 anos)
•Data da primeira mentruação (menarca)

E.5.2.1

Timepoint(s) of evaluation of this end point

At several time during the trial depending the secondary enpoints

Várias vezes durante o ensaio em função dos resultados secundários

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

Yes

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

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

Belgium

Brazil

France

Germany

Mexico

Portugal

South Africa

Spain

Switzerland

Thailand

Uganda

Ukraine

United Kingdom

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

LVLS

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 months

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

F.1.1

Number of subjects for this age range:

300

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

Yes

F.1.1.5.1

Number of subjects for this age range:

120

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

180

F.1.2

Adults (18-64 years)

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Children aged 6 to < 18 years old.

Crianças com idades entre 6 <18 anos.

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

100

F.4.2.2

In 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)

If the HIV-1 viral load remains suppressed, the participant can continue with the current strategy at the discretion of the responsible physician and after discussion with families or switch to a regimen equivalent to the current regimen in efficacy and safety.

Se a carga viral HIV-1 permanecer reprimida, o participante pode continuar com a estratégia atual ou mudar para um regime equivalente ao regime atual de eficácia e segurança de acordo com a decisão do médico responsável e após discussão com a família.

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1
G.4.1	Name of Organisation	Inserm SC10-US19
G.4.3.4	Network Country	France
G.4 Investigator Network to be involved in the Trial: 2
G.4.1	Name of Organisation	MRC CTU
G.4.3.4	Network Country	United Kingdom
G.4 Investigator Network to be involved in the Trial: 3
G.4.1	Name of Organisation	PHPT-IRD 174
G.4.3.4	Network Country	Thailand

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2016-04-21

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-07-11

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2020-10-01

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