Clinical Trials Register

Summary
EudraCT Number:	2013-001476-37
Sponsor's Protocol Code Number:	PENTA17-ANRS152
National Competent Authority:	France - ANSM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2017-10-20
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

France - ANSM

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: Stratégie de maintenance de la supression virale du VIH avec
un inhibiteur d'integrase administré 1 fois/jour + darunavir/ritonavir chez les enfants infectés par le VIH-1 (PENTA 17)
Etude randomisée, ouverte, de phase 2/3 multicentrique, à deux bras d'étude, évaluant la sécurité et l'efficacité d'un inhibiteur d'intégrase administré 1 fois/jour en association avec darunavir/ritonavir (DRV/r) comparé à un traitement antirétroviral standard chez les enfants infectés par le VIH-1 contrôlés virologiquement.

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: Stratégie de maintenance de la supression virale du VIH avec un inhibiteur d'intégrase administré 1 fois/jour en association avec darunavir/ritonavir chez les enfants infectés par le VIH-1 (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-ANRS152

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 Inc
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	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

Infection par le VIH-1 chez des patients pédiatriques

E.1.1.1

Medical condition in easily understood language

Paediatric HIV-1 Infection

Infection par le VIH-1 chez des patients pédiatriques

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.

Evaluer si les enfants, infectés par le VIH-1 présentant une charge virale indétectable et sous trithérapie standard maintiennent un niveau de suppression de la charge virale similaire avec un traitement composé d'un inhibiteur de l'intégrase administré 1 fois/jour en association avec darunavir/r (INSTI+DRV/r) en comparaison à une trithérapie standard.

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.

- Evaluer les effets de la combinaison INSTI+DRV/r sur la progression de la maladie, les paramètres immunologiques, la toxicité mitochondriale, le profil lipidique, la densité minérale osseuse, l'adhérence, l'acceptabilité et la qualité de vie en comparaison avec une trithérapie actuelle standard.
- Caractériser l'exposition au DVR/r+INSTI et les intéractions entre les médicaments.

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 pharmacokinetic parameters of darunavir (DRV), ritonavir (RTV) and INSTI.

1) Sous-étude toxicité mitochondriale
Objectifs: Caractériser les profils d'expression des marqueurs spécifiques de la toxicité mitochondriale entre les 2 groupes de l'étude.
2) Sous-étude Lipides/Densité minérale osseuse (DMO)
Objectifs:
-Documenter le développement et la progression du syndrome lipodystrophique dans une sous-population d'enfants.
-Evaluer l'effet d'une simplification de la trithérapie standard sur la densité minérale osseuse chez des enfants infectés par le VIH-1.
3) Virologie
Objectifs: Les analyses biologiques suivantes (résistance, plasma VIH-1, niveau ARN ou charge virale) seront réalisées localement afin d'évaluer si un régime composé d'un inhibiteur d'intégrase administré 1 fois/jour en association avec DRV/r en comparaison avec une trithérapie standard, chez des enfants infectés par le VIH-1 permet de maintenir un niveau de charge virale similaire.
4) Sous-étude de modélisation de l'exposition au DRV/r+INSTI
Objectifs: Déterminer les paramètres pharmacocinétiques du darunavir (DRV), ritonavir (RTV) et de l'inhibiteur d'integrase (INSTI).

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.Enfants infectés par le VIH-1 âgés d'au moins 12 ans et pesant au minimum 40 kg* à la visite de screening
2.Âgés de 6 ans à 18 ans **
3.Parents/Tuteur légal et Enfants doivent avoir donné leur consentement et être capable d’adhérer au protocole
4.Avoir toutes les charges virales des 12 derniers mois <50cps/ml dont au minimum 2 charges virales distinctes avant le screening
5.Être sous une trithérapie composée d' IP/r ou de NNRTI depuis au moins 24 semaines
6.Parents/Tuteur légal et Enfants doivent être préparés à changer de traitement si l'enfant est randomisé dans le groupe 1 (darunavir/r + INSTI)
7. Parents/Tuteur légal et Enfants doivent être préparés à ce que l'enfant revienne à un traitement antirétroviral standard si les critères de reprise sont atteints
8. Etre affilié ou bénéficaire à un système de sécurité sociale

*. Dans un premier temps, seuls les participants âgés d'au moins 12ans et pesant au minimum 40kg pourront être inclus dans l'essai.
**. Lorsque des données pharmacologiques supplémentaires pour les plus jeunes enfants seront disponibles, un amendement au protocole est prévu pour inclure les participants âgés entre 6-12 ans et pesant moins de 40kg.

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.Recevoir ou avoir besoin de médicaments interagissant avec le DRV, RTV, ou un inhibiteur d'intégrase
2.Avoir une résistance vis-à-vis du DRV ou des inhibiteurs d’intégrase
3.Avoir déjà été exposé aux inhibiteurs d’intégrase pendant plus de 2 semaines
4.Avoir une maladie intercurrente. L'inclusion pourra avoir lieu après résolution de la maladie.
5.Créatinine ≥ 1.8N ou ALAT ≥5N ou ALAT ≥ 3N et bilirubine ≥ 2N au moment du screening
6. Avoir une maladie sévère du foie
7.Avoir une tuberculose et être sous traitement anti-tuberculeux
8.Avoir une hépatite B ou C
9.Etre enceinte ou risque de grosses. Un moyen de contraception efficace est nécessaire pour les femmes en âge de procréer.
10.Antécédents ou présence d'une allergie connue ou autres contraindications avec les médicaments à l'étude ou avec leurs composants mentionnés dans les RCPs.

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)

Pourcentage de patients avec VIH-1 RNA ≥ 50 c/mL (confirmée dans les 4 semaines)

E.5.1.1

Timepoint(s) of evaluation of this end point

Any time up to week 48

Pendant les 48 semaines de participation

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)
-Percentage of patients with 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
-Change in blood lipids from baseline to weeks 24 and 48
-Adherence as measured by questionnaire and visual analogue scale
-Acceptability and quality of life over 48 weeks as assessed by patient completed questionnaires
-Height and weight
-Tanner scales (in participants aged over 8 years)
-Date of first menses

•Pourcentage de patients avec VIH-1 RNA ≥50 c/mL aux semaines 24 et 48
•Pourcentage de patients avec VIH-1 RNA ≥400 c/mL aux semaines 24 et 48
•Pourcentage de patients avec des effets indésirables cliniques de grade 3 ou 4 (particulièrement la lipodystrophie)
•Pourcentage de patients avec des effets indésirables biologiques de grade 3 ou 4
•Tout effet indésirable entrainant un arrêt ou une modification du régime de traitement.
•Présence de mutations conduisant à une résistance aux médicaments définie dans la liste IAS-USA
•Évolution des CD4 (valeur absolue et %) entre le début de l’essai et les semaines 24 et 48
•Modifications du traitement antirétroviral (défini comme tout changement d'ART à partir de la randomisation)
•Tout évènement nouveau ou récurrent de stade CDC C, CDC B sévère ou décès
•Modification du profil lipidique dans le sang entre le début de l’essai et les semaines 24 et 48
•Adhérence évaluée par des questionnaires et des échelles visuelles analogiques
•Acceptabilité et qualité de vie après 48 semaines à travers des questionnaires
•Poids, taille
•Echelle de Tanner (pour les enfants de plus de 8 ans)
•Date des premières règles.

E.5.2.1

Timepoint(s) of evaluation of this end point

At several time during the trial depending the secondary endpoints.

Plusieurs fois pendant l'étude en fonction des résultats secondaires.

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

Enfants âgés de 6 à 18 ans

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.

Dans la cas où la charge virale reste indécelable, le participant pourra soit continuer la stratégie de l'essai ou reprendre un régime de traitement équivalent en efficacité et sécurité en accord avec la décisison du clinicien et après discussion avec la famille.

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

2017-10-03

Ethics Committee Opinion of the trial application

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

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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Orphan Designation Number:
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