Clinical Trials Register

Summary
EudraCT Number:	2013-001476-37
Sponsor's Protocol Code Number:	PENTA17
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2015-10-05
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

Spain - AEMPS

A.2

EudraCT number

2013-001476-37

A.3

Full title of the trial

SMILE: Strategy for Maintenance of HIV suppression with elvitegravir+darunavir/ritonavir in children (PENTA 17) -
A two-arm, Phase 2/3 multicentre, open-label, randomised study evaluating safety and antiviral effect of current standard antiretroviral therapy compared to elvitegravir (EVG) administered with darunavir/ritonavir (DRV/r) in HIV-1 infected, virologically suppressed paediatric participants.

SMILE: Estrategia para el mantenimiento de la supresión del VIH en niños con elvitegravir+darunavir/ritonavir (PENTA 17) -
Estudio abierto aleatorizado de fase II/III, multicéntrico, con dos grupos, que evalúa la toxicidad y el efecto antiviral de las actuales terapias antirretrovirales estándares en comparación con el elvitegravir (EVG) administrado junto a darunavir/ritonavir (DRV/r) en pacientes pediátricos infectados por el VIH-1 con supresión viral.

A.3.1

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

SMILE: Strategy for Maintenance of HIV suppression with elvitegravir+darunavir/ritonavir in children (PENTA 17)

SMILE: Estrategia para el mantenimiento de la supresión del VIH en niños con elvitegravir+darunavir/ritonavir (PENTA 17)

A.3.2

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

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/310/2013

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.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	alexandra.compagnucci@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.3.4	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.3.4	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	up to
D.3.10.3	Concentration number	675
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.3.4	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	675
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.3.4	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	Yes
D.2.1.1.1	Trade name	Vitekta
D.2.1.1.2	Name of the Marketing Authorisation holder	Gilead Sciences International 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.3.2	Product code	GS-9137
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	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	85
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	Vitekta
D.2.1.1.2	Name of the Marketing Authorisation holder	Gilead Sciences International 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.3.2	Product code	GS-9137
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	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.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

Infeccion por el VIH en la poblacion pediatrica

E.1.1.1

Medical condition in easily understood language

Paediatric HIV-1 Infection

Infeccion por el VIH en la poblacion pediatrica

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	18.0
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 wether children with chronic HIV infection on ART with suppressed viral load will maintain similar levels of suppression with elvitegravir+ darunavir/r (EVG+DRV/r) compared to current standard of care triple ART.

Evaluar si los niños con infección crónica por el VIH que están en tratamiento antirretroviral (TAR) y presentan supresión de la carga viral mantendrán, usando elvitegravir + darunavir/r, niveles de supresión similares a aquellos que tendrían si continuaran con el tratamiento según guías habituales.

E.2.2

Secondary objectives of the trial

- To evaluate the PK of EVG+DRV/r
- To evaluate the impact on clinical progression, inmmunovirological parameters, mitochondrial toxicity, lipid profile, bone mineral density, adherence, acceptability and quality of life of the Dual combination of EVG+DRV/r compared to current standard of care triple ART.

- Evaluar los parametros FC del EVG+DRV/r
- Evaluar el impacto en la progresión clínica, los parámetros inmunovirologicos, la toxicidad mitocondrial, el perfil lipídico, la densidad mineral ósea, la adherencia, la aceptabilidad y la calidad de vida con la terapia EVG+DRV/r en comparación con el tratamiento triterapia según guías habituales.

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

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

1) Pharmacokinetics (PK) Substudy
Objectives: To determine the pharmacokinetics of darunavir (DRV), ritonavir (RTV) and elvitegravir (EVG)
2) Mitochondrial substudy
Objectives: To demonstrate differences in markers of mitochondrial toxicity between arms
3) Lipids/Bone Mineral Density (BMD) substudy
Objectives:
- To document the development and the progression of the lipodystrophy syndrome in a subset of children
-To evaluate the impact of ART simplification on changes of BMD in HIV-infected children.
4) Virology
Objectives: The laboratory tests (resistance testing & Plasma HIV-1 RNA levels or viral load) will be performed locally with the objective to study if the simplified regimen of EVG administered with DRV/r compared to standard NNRTI or PI-based 3-drug ART in HIV infected children maintain similar level of viral load.

1) Subestudio FC
Objectivos: Determinar los parámetros farmacocineticos del darunavir (DRV), ritonavir (RTV) y elvitegravir (EVG)
2) Subestudio de toxicidad mitocondrial
Objectivos: Demostrar las diferencias entre los marcadores de la toxicidad mitocondrial ente los brazos
3) Subestudio del perfil lipídico/densidad mineral ósea (DMO)
- Documentar el desarrollo y progresión del síndrome de lipodistrofia en un subconjunto de niños
- Evaluar el impacto de la simplificación de TAR en los cambios de DMO en los niños infectados por VIH.
4)Virología
Objectivos:
Las siguientes pruebas de laboratorio serán realizadas localmente con el objetivo de investigar si el régimen simplificado de EVG
administrado con DRV/r comparándolo con los regímenes antirretrovirales estándar basados en 3 medicamentos (PI+2INTI o
INNTI+2INTI) en niños infectados con el VIH mantienen similar nivel de carga viral en sangre.

E.3

Principal inclusion criteria

1.HIV-1 infected children weighting > 17 kg at the screening visit
2.Aged 6 to < 18 years old
3.Parents or guardians, and children where appropriate, willing and able to give informed consent and to adhere to the protocol
4.Children must have all HIV-1 RNA viral loads <50c/mL for at least 12 months with a minimum of two separate results before screening.
5.Children on a 3-drug PI/r or NNRTI containing regimen for at least 6 months.
6.Children/parents/guardians prepared to switch if randomised to elvitegravir + darunavir/ritonavir arm
7.Children and parents prepared to restart the current ART regimen after simplification if viral load restart criteria are met
8.For children aged 6-12 either:
-children and caregivers are willing to participate in the lead-in PK study if the child is aged 6-12 and the PK study (for children randomised to Arm 1) is still enrolling children in their weight band OR
- Data from the lead-in PK study have been analysed and children aged 6-12 can be enrolled directly into the main study

1.Niños infectados por el VIH-1 con un peso igual o superior a 17 kg en el momento de la visita de selección.
2.Niños con al menos 6 años y menores de 18 años.
3.Los padres o tutores y los niños, si procede, están dispuestos y son capaces de dar su consentimiento informado y cumplir con el protocolo.
4.Todos los niños deben haber tenido una carga viral VIH-1 ARN <50 c/ml durante, al menos, los últimos 12 meses, con un mínimo de dos resultados separados anteriores a la selección.
5.Los niños deben haber seguido una pauta de tres fármacos, uno de los cuales es un IP/r o un ITIAN, durante al menos los 6 últimos meses.
6.Los niños/padres/tutores están preparados para cambiar de tratamiento en el caso de que sean asignados aleatoriamente al grupo de elvitegravir + darunavir/ritonavir.
7.Tras la simplificación, los niños y los padres están preparados para retomar el TAR actual si se cumplen los criterios de carga viral.
8.Para niños con edades comprendidas entre los 6 y los 12 años, o bien:
- los niños y sus tutores están dispuestos a participar en el estudio FC preliminar si el niño tiene entre 6 y 12 años y el estudio FC (para los pacientes randomizados en el brazo EVG/DRV/r) aún está reclutando niños en esa banda de peso, O BIEN
- se han analizado los datos del estudio FC y los niños con edades comprendidas entre los 6 y los 12 años pueden inscribirse directamente en el estudio principal.

E.4

Principal exclusion criteria

1.Receiving or requiring agents with interactions with darunavir, RTV, or EVG
2.Evidence of resistance to DRV or integrase inhibitors
3.Previous exposure to integrase inhibitors for more than 2 weeks
4.History of previous encephalopathy
5.Intercurrent illness
6.Creatinine, AST or ALT of grade 3 or above at screening.
7.Diagnosis of tuberculosis and on anti-tuberculosis treatment
8.Hepatitis B or Hepatitis C co-infection
9.Pregnancy or risk of pregnancy in girls of child-bearing potential unless committed to taking effective contraception

1.Reciben o necesitan agentes que interaccionan con darunavir, RTV o EVG.
2.Hay indicios de resistencia al DRV o a inhibidores de la integrasa.
3.Han recibido tratamiento previo de inhibidores de la integrasa durante más de 2 semanas.
4.Antecedente de encefalopatía.
5.Enfermedad intercurrente.
6.Creatinina, AST o ALT de grado 3 o superior en el momento de la selección.
7.Diagnóstico de tuberculosis y en tratamiento para tuberculosis.
8.Hepatitis B o coinfección con Hepatitis C.
9.Embarazo o riesgo de embarazo en niñas en edad reproductiva, a menos que se comprometan a tomar anticonceptivos efectivos.

E.5 End points

E.5.1

Primary end point(s)

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

Porcentaje de pacientes con VIH-1 ARN ≥50 c/ml (confirmado en 4 semanas)

E.5.1.1

Timepoint(s) of evaluation of this end point

Any time up to week 48

En todo momento hasta la semana 48

E.5.2

Secondary end point(s)

-Percentage of patients with HIV-1 RNA < 50 c/mL at week 48
-Percentage of patients with HIV-1 RNA > 50 c/mL at week 24 and week 48
-Percentage of patients with HIV-1 RNA > 400c/mL at week 24 and week 48
-All grade 3 or 4 clinical adverse events (particularly lipodystrophy)
-All grade 3 or 4 laboratory adverse events
-Any adverse event at least possibly related to study drugs or leading to treatment modifications
-Occurrence of new major and minor resistance mutations defined by the current IAS-USA list
-Changes in CD4 from baseline to weeks 24 and 48
-Change in ART (defined as any change from the ART regimen at randomisation)
-New or recurrent CDC/WHO stage C or severe stage B event or death
-Change in blood lipids from baseline to weeks 24 and 48
-Adherence as measured by questionnaire and visual analogue scale
-Acceptability and quality of life over 48 weeks as assessed by patient completed questionnaires
-Height and weight; Tanner scales (in participants aged over 8 years)
-date of first menses

-Porcentaje de pacientes con VIH-1 ARN <50 c/ml a la semana 48
-Porcentaje de pacientes con VIH-1 ARN ≥50 c/ml a la semana 24 y 48
-Porcentaje de pacientes con VIH-1 ARN ≥400 c/ml a las semanas 24 y 48
-Todos los acontecimientos adversos de carácter clínico de grado 3 ó 4 (en particular la lipodistrofia)
-Todos los acontecimientos adversos a nivel de laboratorio de grado 3 ó 4
-Cualquier acontecimiento adverso que pueda estar relacionado con los fármacos del estudio o que haga necesario modificar el tratamiento
-Aparición de nuevas mutaciones de resistencia tal como se definen en la lista IAS-USA corriente
-Cambios en los niveles de CD4 (absolutos y porcentuales) desde el momento del inicio del estudio hasta las semanas 24 y 48
-Modificaciones del TAR (definidos como cualquier cambio en la pauta posológica del TAR en el momento de la aleatorización)
-Un acontecimiento nuevo o recurrente de estadio C o de estadio B grave según la CDC/OMS o un fallecimiento
-Cambios en los parámetros lipídicos a partir del inicio hasta las semanas 24 y 48
-Adherencia, medida a través de cuestionarios y escala análoga visual
-Aceptabilidad y calidad de vida en el transcurso de 48 semanas, valoradas a través de los cuestionarios cumplimentados por los pacientes
-Altura y peso; estadios de Tanner (en los pacientes de más de 8 años)
-Fecha de la primera menstruación

E.5.2.1

Timepoint(s) of evaluation of this end point

At several time during the trial depending the secondary enpoints (Describe in E.5.2)

En varias veces durante el ensayo segun los criterios secundarios de valoración (ver E.5.2)

E.6 and E.7 Scope of the trial

E.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

Denmark

France

Germany

Ireland

Italy

Mexico

Netherlands

Poland

Portugal

Romania

South Africa

Spain

Sweden

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 under 18 years old.

Ninos menos de 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)

Drugs will be supplied by collaborating pharmaceutical companies or PENTA free of charge to participants deriving benefit until they become available locally.

Las compañías farmacéuticas colaboradoras o PENTA suministrarán los fármacos a los participantes de forma gratuita hasta que estos estén disponibles a nivel local.

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1
G.4.1	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

2015-12-16

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-11-05

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2021-11-17

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