Clinical Trials Register

Summary
EudraCT Number:	2021-005927-19
Sponsor's Protocol Code Number:	GESIDA11920
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2022-03-02
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Spain - AEMPS

A.2

EudraCT number

2021-005927-19

A.3

Full title of the trial

Phase IV, randomized, multicenter, double-blind clinical trial designed to evaluate the safety and convenience of switching from Dolutegravir/Lamivudine to Bictegravir/Emtricitabine/Tenofovir alafenamide in people with HIV, good virological control and neuropsychiatric vulnerabilities: MIND study

Ensayo clínico fase IV, aleatorizado, multicéntrico y doble ciego diseñado para evaluar la seguridad y la conveniencia del cambio de Dolutegravir/Lamivudina por Bictegravir/Emtricitabina/Tenofovir alafenamida en personas con VIH, buen control virológico y vulnerabilidades neuropsiquiátricas: Estudio MIND

A.3.1

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

Clinical trial designed to evaluate the safety and convenience of switching from Dolutegravir/Lamivudine to Bictegravir/Emtricitabine/Tenofovir alafenamide in people with HIV, good control and neuropsychiatric vulnerabilities: MIND study

Ensayo clínico para evaluar la seguridad y la conveniencia del cambio de Dolutegravir/Lamivudina por Bictegravir/Emtricitabina/Tenofovir alafenamida en personas con VIH, buen control y vulnerabilidades neuropsiquiátricas: Estudio MIND

A.3.2

Name or abbreviated title of the trial where available

MIND

A.4.1

Sponsor's protocol code number

GESIDA11920

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	Fundación SEIMC-GESIDA
B.1.3.4	Country	Spain
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	Gilead Sciences S.A
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Dynamic Science S.L.
B.5.2	Functional name of contact point	Miriam Pérez Marcos
B.5.3	Address:
B.5.3.1	Street Address	Calle Azcona 31
B.5.3.2	Town/ city	Madrid
B.5.3.3	Post code	28028
B.5.3.4	Country	Spain
B.5.4	Telephone number	0034914561105
B.5.5	Fax number	0034914561126
B.5.6	E-mail	m.perez@evidenze.com

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	Biktarvy
D.2.1.1.2	Name of the Marketing Authorisation holder	Biktarvy
D.2.1.2	Country which granted the Marketing Authorisation	Spain
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	Biktarvy
D.3.2	Product code	EU/1/18/1289/004
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	Bictegravir
D.3.9.1	CAS number	SUB182699
D.3.9.2	Current sponsor code	Gilead
D.3.9.3	Other descriptive name	Bictegravir
D.3.9.4	EV Substance Code	SUB182699
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	50
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Emtricitabine
D.3.9.1	CAS number	143491-57-0
D.3.9.2	Current sponsor code	Gilead
D.3.9.3	Other descriptive name	Emtricitabine
D.3.9.4	EV Substance Code	SUB01882MIG
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	200
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	TENOFOVIR ALAFENAMIDE
D.3.9.1	CAS number	379270-37-8
D.3.9.2	Current sponsor code	Gilead
D.3.9.3	Other descriptive name	TENOFOVIR ALAFENAMIDE
D.3.9.4	EV Substance Code	SUB121761
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	25
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 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	DOVATO
D.2.1.1.2	Name of the Marketing Authorisation holder	ViiV Healthcare BV
D.2.1.2	Country which granted the Marketing Authorisation	Spain
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	Dovato
D.3.2	Product code	EU/1/19/1370/002
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	DOLUTEGRAVIR SODIUM
D.3.9.1	CAS number	SUB130591
D.3.9.2	Current sponsor code	ViiV Healthcare BV
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.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Lamivudine
D.3.9.1	CAS number	134678-17-4
D.3.9.2	Current sponsor code	ViiV Healthcare BV
D.3.9.3	Other descriptive name	Lamivudine
D.3.9.4	EV Substance Code	SUB08392MIG
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	200
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Tablet
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Human immunodeficiency virus

Virus de la inmunodeficiencia humana

E.1.1.1

Medical condition in easily understood language

Human immunodeficiency virus

Virus de la inmunodeficiencia humana

E.1.1.2

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10053500
E.1.2	Term	Human immunodeficiency virus transmission
E.1.2	System Organ Class	10021881 - Infections and infestations

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To compare the safety of switching to Bictegravir/Emtricitabine/Tenofovir alafenamide versus continuing treatment with Dolutegravir/Lamivudine.

Comparar la seguridad del cambio a Bictegravir/Emtricitabina/Tenofovir alafenamida frente a continuar tratamiento con Dolutegravir/Lamivudina.

E.2.2

Secondary objectives of the trial

To compare the convenience of switching to Bictegravir/Emtricitabine/Tenofovir alafenamide versus continuing treatment with Dolutegravir/Lamivudine.

Comparar la conveniencia del cambio a Bictegravir/Emtricitabina/Tenofovir alafenamida frente a continuar tratamiento con Dolutegravir/Lamivudina.

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

To compare brain integrity and functionality before and after switching to Bictegravir/Emtricitabine/Tenofovir alafenamide. Primary endpoint: Changes in brain volumes.
Secondary endpoints:
1) Changes in the levels of N-acetyl-aspartate, choline and myo-inositol at the level of the frontal gray matter, the frontal white matter and the basal ganglia.
2) Changes in the integrity of the white matter.
3) Changes in cerebral perfusion.
4) Changes in the resting state of the brain.
Primary analysis: Week 48.
Study population: Participants in the neuroimaging substudy.

Comparar la integridad y la funcionalidad cerebral antes y después del cambio a Bictegravir/Emtricitabina/Tenofovir alafenamida. Endpoint primario: Cambios en los volúmenes cerebrales.
Endpoint secundarios:
1) Cambios en los niveles de N-acetil-aspartato, colina y mioinositol a nivel de la sustancia gris frontal, de la sustancia blanca frontal y de los ganglios basales.
2) Cambios en la integridad de la sustancia blanca.
3) Cambios en la perfusión cerebral.
4) Cambios en el estado de reposo cerebral.
Análisis primario: Semana 48.
Población de estudio: Participantes en el subestudio de neuroimagen.

E.3

Principal inclusion criteria

• Adult >18 years old diagnosed with HIV by standard microbiological techniques.
• Active antiretroviral treatment with Dolutegravit/Lamivudine.
• Last HIV viral load performed on the participant in the 6 months prior to the screening visit < 50 copies/mL. If the participant does not have an HIV viral load <50 cop/mL performed in the 14 days prior to the screening visit, it will be necessary to confirm at the screening visit that the participant's HIV viral load is <50 cop/mL .
• Previous clinical diagnosis of any of the following pathologies:
or insomnia
or anxiety disorders
or depressive disorders

• Adulto >18 años diagnosticado de VIH mediante técnicas microbiológicas habituales.
• Tratamiento antirretroviral activo con Dolutegravit/Lamivudina.
• Última carga viral de VIH realizada al participante en los 6 meses previos a la visita de screening < 50 copias/mL. Si el participante no dispone de una carga viral de VIH <50 cop/mL realizada en los 14 días previos a la visita de selección, será necesario confirmar en la visita de selección que la carga viral de VIH del participante es <50 cop/mL.
• Diagnóstico clínico previo de alguna de las siguientes patologías:
o Insomnio
o Trastornos de ansiedad
o Trastornos depresivos

E.4

Principal exclusion criteria

• Allergy or intolerance to any of the components of Bictegravir/Emtricitabine/Tenofovir alafenamide.
• History of active central nervous system infections.
• Active psychosis or suicidal ideation
• Pregnant or lactating women, as well as women of childbearing age who do not agree to use at least two contraceptive methods.
• Any clinical or laboratory condition that in the opinion of the investigator will prevent the participant from completing the study procedures.
• Participant included in the neuroimaging substudy: Claustrophobia or presence of magnetizable body devices.

• Alergia o intolerancia a cualquiera de los componentes de Bictegravir/Emtricitabina/Tenofovir alafenamida.
• Historia de infecciones activas del sistema nervioso central.
• Psicosis activa o ideación autolítica
• Mujeres embarazadas o lactantes, así como mujeres en edad fértil que no se comprometan a utilizar al menos dos métodos contraceptivos.
• Cualquier condición clínica o de laboratorio que a opinión del investigador van a impedir al participante completar los procedimientos del estudio.
• Participante incluidos en el subestudio de neuroimagen: Claustrofobia o presencia de dispositivos corporales magnetizables.

E.5 End points

E.5.1

Primary end point(s)

- Proportion of grade 2-4 neuropsychiatric adverse effects.
- Proportion of grade 2-4 adverse effects.
- Proportion of antiretroviral treatment discontinuations due to neuropsychiatric adverse effects.
- Proportion of antiretroviral treatment discontinuations for any reason.

- Proporción de efectos adversos neuropsiquiátricos grado 2-4.
- Proporción de efectos adversos grado 2-4.
- Proporción de discontinuaciones del tratamiento antirretroviral por efectos adversos neuropsiquiátricos.
- Proporción de discontinuaciones del tratamiento antirretroviral por cualquier causa.

E.5.1.1

Timepoint(s) of evaluation of this end point

Endpoints will be continuously assessed during the clinical trial at Week 24 and Week 48 for grade 2-4 neuropsychiatric adverse events and grade 2-4 adverse events and reasons for antiretroviral treatment discontinuation.

Las variables serán evaluadas de forma continua durante el ensayo clínico en la Semana 24.
y la Semana 48 de acontecimientos adversos neuropsiquiatricos grado 2-4 y Acontecimientos adversos grado 2-4 y motivos de discontinuación del tratamiento antiretroviral.

E.5.2

Secondary end point(s)

- Changes in sleep quality estimated using the Pittsburgh Sleep Quality Questionnaire (PSQI).
- Changes in mood estimated using the Hospital Anxiety and Depression Scale (HADS).
- Changes in the scale of satisfaction with ART (ESTAR).
- Changes in the Spanish version of the MOS-HIV quality of life questionnaire.

- Cambios en la calidad del sueño estimada mediante el cuestionario de calidad del sueño de Pittsburg (PSQI).
- Cambios en el estado anímico estimado mediante la escala hospitalaria de ansiedad y depresión (HADS).
- Cambios en la escala de satisfacción con el TAR (ESTAR).
- Cambios en la versión española del cuestionario de calidad de vida MOS-HIV.

E.5.2.1

Timepoint(s) of evaluation of this end point

The variables will be continuously evaluated during the clinical trial at Week 24 and Week 48 by evaluating the Pittsburgh Sleep Quality Questionnaire, the Hospital Anxiety and Depression Scale, the STAR Scale, and the MOS-HIV Quality of Life Questionnaire.

Las variables serán evaluadas de forma continua durante el ensayo clínico en la Semana 24 y Semana 48 evaluando el cuestionario de calidad del sueño de Pittsburg , la escala hospitalaria de ansiedad y depresión, la escala STAR y el cuestionario de calidad de vida MOS-HIV

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

E.6.4

Safety

Yes

E.6.5

Efficacy

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

Yes

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

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)

E.8.2.2

Placebo

Yes

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

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

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

Última visita del último paciente

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

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

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)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

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

F.3.3.1

Women of childbearing potential not using contraception