Clinical Trials Register

Summary
EudraCT Number:	2018-003458-26
Sponsor's Protocol Code Number:	DEBATE
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2020-10-07
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

Italy - Italian Medicines Agency

A.2

EudraCT number

2018-003458-26

A.3

Full title of the trial

Evaluating inflammatory and immunological changes of HIV-positive patients switching to DTG dual regimen compared to those switching to a triple drugs regimen (B/F/TAF).

Valutazione dei cambiamenti a livello infiammatorio e immunologico nei pazienti con infezione da HIV che passano a un doppio regime terapeutico contenente DTG rispetto a quelli che passano a un triplo regime (B/F/TAF).

A.3.1

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

Evaluating inflammatory and immunological changes of HIV-positive patients switching to DTG dual regimen compared to those switching to a triple drugs regimen (B/F/TAF).

A.3.2

Name or abbreviated title of the trial where available

DEBATE

A.4.1

Sponsor's protocol code number

DEBATE

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	AZIENDA OSPEDALIERO-UNIVERSITARIA DI MODENA
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	Gilead Sciences Inc.
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	Azienda Ospedaliero Universitaria Policlinico di Modena
B.5.2	Functional name of contact point	Ufficio Sperimentazioni Cliniche
B.5.3	Address:
B.5.3.1	Street Address	via del Pozzo 71
B.5.3.2	Town/ city	Modena
B.5.3.3	Post code	41124
B.5.3.4	Country	Italy
B.5.4	Telephone number	+390594223673
B.5.5	Fax number	+390594222604
B.5.6	E-mail	nb.protocolli@unimore.it

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Comparator
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.2.5	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	lamivudina
D.3.2	Product code	[3TC]
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	LAMIVUDINA
D.3.9.1	CAS number	134678-17-4
D.3.9.2	Current sponsor code	3TC
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	300
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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	Comparator
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.2.1.2	Country which granted the Marketing Authorisation	Netherlands
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.3.2	Product code	[DTG]
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
D.3.9.1	CAS number	1051375-19-9
D.3.9.2	Current sponsor code	DTG
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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	Biktarvy
D.2.1.1.2	Name of the Marketing Authorisation holder	Gilead Sciences International Ltd.
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
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	bictegravir/emtricitabina/tenofovir alafenamide fumarato
D.3.2	Product code	[B/F/TAF]
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	bictegravir
D.3.9.1	CAS number	1611493-60-7
D.3.9.2	Current sponsor code	BIC
D.3.9.3	Other descriptive name	bictegravir
D.3.9.4	EV Substance Code	SUB 182699
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	EMTRICITABINA
D.3.9.1	CAS number	143491-57-0
D.3.9.2	Current sponsor code	FTC
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	TAF
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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

HIV infection

infezione da HIV

E.1.1.1

Medical condition in easily understood language

HIV infection

infezione da HIV

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 the CD8 slope and consequent CD4/CD8 ratio in HIV-positive patients switching to bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) vs. those who switch to dolutegravir + lamivudine (DTG+3TC).

Valutare l’andamento dei CD8 e conseguentemente il rapporto CD4/CD8 nei pazienti con infezione da HIV che passano a bictegravir/emtricitabina/tenofovir alafenamide (B/F/TAF) rispetto a quelli che passano a dolutegravir+lamivudina (DTG+3TC)

E.2.2

Secondary objectives of the trial

To identify changes in inflammation and immune characteristics among HIV-patients and correlate the inflammatory and immunological data with the type of regimen in order to find early biomarkers to drive the therapeutic decision.

Identificare i cambiamenti a livello infiammatorio e immunologico caratteristici tra i pazienti con infezione da HIV e correlare i dati infiammatori e immunologici al tipo di regime, al fine di identificare biomarcatori precoci in grado di indirizzare la decisione terapeutica.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1) Age = 18 years
2) The ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures
3) Patients infected by HIV-1
4) Patients under the first-line cART regimen with three antiretrovirals
5) HIV-RNA <=50 copies/mL for at least 12 months
6) No previous virological failures/blips
7) A female subject is eligible to enter the study if it is confirmed that she is:
- Not pregnant or nursing
- Of non-childbearing potential (e.g., women who have had a hysterectomy, have had both ovaries removed or medically documented ovarian failure, or are postmenopausal women >54 years of age with cessation for =12 months of previously occurring menses)
- Of chilbearing potential and agrees to utilize highly effective contraception methods or be non-heterosexually active or practice sexual abstinence from screening throughout the duration of study treatment and for 30 days following discontinuation of study drugs
- Female subjects who utilize hormonal contraceptive as one of their birth control methods must have used the same method for at least three months prior to study dosing
8) Male subjects must agree to utilize a highly effective method of contraception (as defined in Appendix 5) during heterosexual intercourse or be non-heterosexually active, or practice sexual abstinence from first dose throughout the study period and for 30 days following the last study drug dose.
9) Male subjects must agree to refrain from sperm donation from first dose until at least 30 days after the last study drug dose.

1) Età = 18 anni
2) Capacità di comprendere e firmare il modulo di consenso informato scritto
3) Infezione da HIV-1
4) Pazienti in regime cART di prima linea con tre antiretrovirali
5) HIV-RNA <=50 copie/mL per almeno 12 mesi
6) Assenza di precedenti blip/fallimenti virologici
7) Un soggetto di sesso femminile potrà essere arruolato nello studio qualora si confermi che:
- Non è in stato di gravidanza o in allattamento
- Non è in età fertile (ad es., donne che abbiano avuto un'isterectomia, donne alle quali sono state rimosse entrambe le ovaie o che abbiano una insufficienza ovarica documentata da un medico, o donne in postmenopausa con età > 54 anni e assenza di mestruazioni da almeno 12 mesi)
- E’ in età fertile e accetta di utilizzare metodi contraccettivi altamente efficaci o di non essere eterosessualmente attiva o di praticare l’astinenza sessuale per l’intera durata del trattamento, a partire dalla data di screening e fino a 30 giorni dopo l’ultima assunzione di farmaco dello studio
- I soggetti femminili che utilizzano contraccettivi ormonali come uno dei metodi di controllo delle nascite devono avere usato il medesimo metodo per almeno tre mesi prima dell’assunzione della prima dose di farmaco dello studio
8) I soggetti di sesso maschile devono accettare di utilizzare un metodo contraccettivo altamente efficace durante i rapporti eterosessuali o di non essere eterosessualmente attivi o di praticare l’astinenza sessuale per l’intera durata del trattamento, a partire dalla data di assunzione della prima dose di farmaco e fino a 30 giorni dopo l’ultima assunzione di farmaco dello studio.
9) I soggetti di sesso maschile devono accettare di astenersi dalla donazione di sperma dalla prima dose fino ad almeno 30 giorni dopo l'ultima dose del farmaco in studio.

E.4

Principal exclusion criteria

1) Patients with chronic hepatitis B
2) Pregnant or breastfeeding women
3) Current alcohol or substance use judged by the Investigator to potentially interfere with subject study compliance
4) Known hypersensitivity to B/F/TAF FDC tablets, DTG and 3TC, their metabolites, or formulation excipient
5) Subjects receiving ongoing therapy with any of the following medications in the table below, including drugs not to be used with B, F, TAF, DTG and 3TC.
Administration of any of the previous medications must be discontinued at least 30 days prior to the Day 1 visit and for the duration of the study
6) Documented resistance to any of the study drugs
7) Active, serious infection (other than HIV-1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to Day 1.
8) Any other clinical condition or prior therapy that, in the opinion of the Investigator, would make the subject unsuitable for the study or unable to comply with protocol requirements.

1) Epatite B cronica
2) Donne in gravidanza o allattamento
3) Uso corrente di alcol o di sostanze che, a discrezione dello sperimentatore, possa potenzialmente interferire con l’aderenza ai requisiti dello studio
4) Ipersensibilità nota alle compresse di B/F/TAF, DTG e 3TC, ai loro metaboliti o a eccipienti di formulazione
5) Soggetti in terapia con farmaci che non devono essere usati in concomitanza con B, F, TAF, DTG e 3TC, a meno che tali farmaci non vengano interrotti almeno 30 giorni prima della visita di arruolamento e non vengano più assunti per tutta la durata dello studio
6) Resistenza documentata ad uno qualsiasi dei farmaci in studio
7) Infezione attiva grave (diversa dall'infezione da HIV-1) che richieda terapia antibiotica o antimicotica per via parenterale entro 30 giorni dalla visita di arruolamento.
8) Qualsiasi altra condizione clinica o terapia precedente che, secondo il parere dello sperimentatore, renderebbe il soggetto inadatto per lo studio o incapace di soddisfare i requisiti del protocollo.

E.5 End points

E.5.1

Primary end point(s)

CD8 slope and consequent CD4/CD8 ratio difference between the 2 arms

Andamento dei CD8 e conseguente differenza nel rapporto CD4/CD8 tra i 2 bracci

E.5.1.1

Timepoint(s) of evaluation of this end point

48 weeks

48 settimane

E.5.2

Secondary end point(s)

To identify molecules and pathways related to changes in immune-inflammatory status and correlate to the regimen.

Identificare le molecole e i meccanismi correlati alle variazioni dello status immuno-infiammatorio e rapportarli al regime terapuetico

E.5.2.1

Timepoint(s) of evaluation of this end point

48 weeks

48 settimane

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

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

Yes

E.6.13.1

Other scope of the trial description

immunological evaluations

valutazioni immunologiche

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

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

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

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

Information not present in EudraCT

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

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

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

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

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

F.4.2.2

In the whole clinical trial

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)

as per clinical practice

come da pratica clinica

G. Investigator Networks to be involved in the Trial

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

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2019-03-25

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-03-05

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2022-07-28

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