Clinical Trials Register

Summary
EudraCT Number:	2017-002855-27
Sponsor's Protocol Code Number:	IN-CA-311-3963/CTN299
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:	2021-06-08
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

2017-002855-27

A.3

Full title of the trial

BonE health in ageING Women: Improvement or prevention of changes in Bone Mineral
Density by Switching Antiretroviral Agents. Is there an optimal time to intervene?

La salute delle ossa nell¿invecchiamento femminile: miglioramento o prevenzione delle variazioni di densit¿ minerale ossea modificando i farmaci antiretrovirali. Esiste un momento ottimale per intervenire?

A.3.1

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

BonE health in ageING Women: Improvement or prevention of changes in Bone Mineral
Density by Switching Antiretroviral Agents. Is there an optimal time to intervene?

A.3.2

Name or abbreviated title of the trial where available

BEING

A.4.1

Sponsor's protocol code number

IN-CA-311-3963/CTN299

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT02815566

A.5.4

Other Identifiers

Name:

BEING

Number:

BEING

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	UNIVERSITY HEALTH NETWORK
B.1.3.4	Country	Canada
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
B.4.2	Country	United States
B.4.1	Name of organisation providing support	Canadian HIV Trials Network
B.4.2	Country	Canada
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Universit¿ di Modena e Reggio Emilia
B.5.2	Functional name of contact point	Dipartimento di Scienze Mediche e C
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	+390594225318
B.5.5	Fax number	+390594223710
B.5.6	E-mail	giovanni.guaraldi@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.2.1.1.1	Trade name	TRUVADA - 30 COMPRESSE RIVESTITE CON FILM IN FLACONE HDPE DA 200 MG/245 MG
D.2.1.1.2	Name of the Marketing Authorisation holder	GILEAD SCIENCE INTERNATIONAL LIMITED
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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	truvada
D.3.2	Product code	J05AR03
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	EMTRICITABINA/TENOFOVIR DISOPROXIL
D.3.9.2	Current sponsor code	truvada
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	445
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.2.1.1.1	Trade name	STRIBILD - 150MG/150MG/200MG/245MG/ - COMPRESSA RIVESTITA CON FILM - USO ORALE - FLACONE (HDPE) - 30 COMPRESSE
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	Italy
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	stribild
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	TENOFOVIR DISOPROXIL FUMARATO
D.3.9.2	Current sponsor code	TENOFOVIR DISOPROXIL FUMARATO
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	245
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	elvitegravir
D.3.9.2	Current sponsor code	elvitegravir
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.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	cobicistat
D.3.9.2	Current sponsor code	cobicistat
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.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	EMTRICITABINA
D.3.9.2	Current sponsor code	EMTRICITABINA
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	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	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.2.1.1.1	Trade name	EVIPLERA - 25MG RILPIVIRINA/200MG EMTRICITABINA/245MG TENOFOVIR DISOPROXIL-COMPRESSA RIVESTITA CON FILM-USO ORALE-FLACONE (HDPE) 30 COMPRESSE
D.2.1.1.2	Name of the Marketing Authorisation holder	GILEAD SCIENCE INTERNATIONAL LIMITED
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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	eviplera
D.3.2	Product code	eviplera
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	EMTRICITABINA/RILPIVIRINA/TENOFOVIR DISOPROXIL
D.3.9.2	Current sponsor code	eviplera
D.3.10	Strength
D.3.10.1	Concentration unit	Other
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1
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: 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	GENVOYA - 150 MG / 150 MG / 200 MG /10 MG- COMPRESSA RIVESTITA CON FILM- USO ORALE- FLACONE (HDPE)- 30 COMPRESSE
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	Italy
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	genvoya
D.3.2	Product code	J05AR18
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	EMTRICITABINA
D.3.9.2	Current sponsor code	EMTRICITABINA
D.3.9.3	Other descriptive name	EMTRICITABINE
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	cobicistat
D.3.9.2	Current sponsor code	cobicistat
D.3.9.3	Other descriptive name	cobicistat
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.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	tenofovir alafenamide
D.3.9.2	Current sponsor code	tenofovir alafenamide
D.3.9.3	Other descriptive name	tenofovir alafenamide
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	10
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	elvitegravir
D.3.9.2	Current sponsor code	elvitegravir
D.3.9.3	Other descriptive name	elvitegravir
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	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: 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	DESCOVY - 200 MG/10 MG- COMPRESSA RIVESTITA CON FILM- USO ORALE- FLACONE (HDPE)- 30 COMPRESSE
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	Italy
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	descovy
D.3.2	Product code	J05AR17
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	EMTRICITABINA/TENOFOVIR alafenamide
D.3.9.2	Current sponsor code	EMTRICITABINA/TENOFOVIR ALAFENAMIDE
D.3.9.3	Other descriptive name	EMTRICITABINA/TENOFOVIR ALAFENAMIDE
D.3.10	Strength
D.3.10.1	Concentration unit	DF dosage form
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1
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: 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	ODEFSEY - 200 MG/25 MG/25 MG- COMPRESSA RIVESTITA- USO ORALE- FLACONE (HDPE) 30 COMPRESSE
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	Italy
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	Odefsey
D.3.2	Product code	J05AR19
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	EMTRICITABINA/RILPIVIRINA/TENOFOVIR ALAFENAMIDE
D.3.9.2	Current sponsor code	EMTRICITABINA/RILPIVIRINA/TENOFOVIR ALAFENAMIDE
D.3.9.3	Other descriptive name	EMTRICITABINA/RILPIVIRINA/TENOFOVIR ALAFENAMIDE
D.3.10	Strength
D.3.10.1	Concentration unit	DF dosage form
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1
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 and menopause

infezione da HIV e menopausa

E.1.1.1

Medical condition in easily understood language

HIV infection and menopause

infezione da HIV e menopausa

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 determine if:
1. Switching HIV+ women on TDF/FTC to TAF/FTC increases BMD at the spine at 48
weeks relative to those who continue TDF/FTC
2. To determine if any observed improvements continue or stabilize in the year after
switch.

1.Valutare a 48 settimane se vi sia un incremento nella BMD dopo il passaggio da un regime contenente TDF/FTC ad uno contenente TAF/FTC, rispetto al mantenimento di TDF/FTC, in donne con infezione da HIV
2. Determinare se i miglioramenti osservati continuino o si stabilizzino nell¿anno successivo allo switch terapeutico

E.2.2

Secondary objectives of the trial

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Biological female aged 45-55
2. Documented HIV-1 infection
3. Peri-menopausal or within 10 years of menopause
4. Signed Informed Consent Form and willing to comply with the protocol.
5. Receiving a cART regimen containing a ritonavir boosted PI (darunavir, atazanavir,
lopinavir,) or an NNRTI (efavirenz, nevirapine or rilpivirine) or an integrase inhibitor
(dolutegravir, raltegravir or elvitegravir) in combination with TDF-FTC for > 24 weeks.
i. Participants on a single tablet regimen containing TDF/FTC are able to
participate as long as they meet the virologic suppression criteria. Those who are on more than 3 agents are eligible provided they meet these
criteria.
6. Stable viral suppression (plasma HIV-RNA<50 copies/mL for > 24weeks). Single viral
blip <500 copies/mL allowed if re-suppresses.
7. If of childbearing potential, is using effective birth control methods and is willing to continue during the trial.
8. Women will be assessed for vitamin D and calcium dietary intake; if inadequate for age, supplements will be recommended.

1. Donne di età compresa tra 45 e 55 anni
2. Infezione documentata da HIV-1
3. Fase peri-menopausale o entro 10 anni dalla menopausa
4. Soggetti in grado di firmare il consenso informato e disposti a rispettare i requisiti del protocollo
5. Assunzione di un regime ARV contenente un PI potenziato con ritonavir (darunavir, atazanavir, lopinavir,) o un NNRTI (efavirenz, nevirapina o rilpilvirine) o un inibitore dell'integrasi (dolutegravir, raltegravir o elvitegravir) in associazione a TDF/FTC dal almeno 24 settimane. Regimi comprendenti più di 3 agenti antiretrovirali sono permessi, purché rientrino nei criteri precedenti.
6. Soppressione virologica stabile (valori di HIV 1-RNA <50 copie / ml da almeno 24 settimane). Un singolo blip virale <500 copie/ml è consentito se successivamente ri-soppresso
7. Se in età fertile, volontà ad utilizzare metodi contraccettivi efficaci durante tutto il periodo dello studio
8. Se, a seguito di valutazione, i valori di vitamina D e di assunzione del calcio con la dieta risultassero inadeguati per età, verranno raccomandati opportuni integratori.

E.4

Principal exclusion criteria

1. HIV-2 infection
2. High 10-year fracture risk at screening ( > 20%) based on country specific FRAX
3. Current treatment with active bone medications- bisphosphonates, denosumab, calcitonin, raloxifene, teriparatide, stontrium
4. Current use of systemic steroids (inhaled steroids permitted) or chemotherapeutic agents
5. Acute viral hepatitis
6. Chronic hepatitis C with AST and/or ALT >5 x ULN or expected to require HCV treatment during the trial period.
7. Any investigational ARV within 30 days screening
8. Dialysis or renal insufficiency (creatinine clearance < 50ml/min)
9. History of decompensated liver disease (AST or ALT=5x the upper limit of normal (ULN) or ALT = 3 x ULN and bilirubin = 1.5 x ULN with > 35% direct bilirubin), or the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal
or gastric varices.
10. Pregnant or breastfeeding
11. Screening blood result with any grade 3/4 toxicity according to Division of AIDS (DAIDS) grading scale, except: asymptomatic grade 3 amylase, CPK, or lipid
elevation.
12. Any condition (including illicit drug use or alcohol abuse) or lab results which, in the investigator’s opinion, interfere with assessments or completion of the trial.

1. Infezione da HIV-2
2. Rischio elevato di frattura a 10 anni al basale (> 20%) calcolato con FRAX TM paese specifico
3. In trattamento con farmaci attivi sull’osso come bifosfonati, denosumab, calcitonina, raloxifene, teriparatide, stronzio
4. In trattamento con steroidi sistemici (steroidi per via inalatoria sono consentiti) o agenti chemioterapici
5. Epatite virale acuta
6. Epatite C cronica con AST e/o ALT> 5 x ULN o che richieda un trattamento anti-HCV durante il periodo di studio
7. Assunzione di farmaci ARV sperimentali nei 30 giorni precedenti lo screening
8. Dialisi o insufficienza renale (clearance della creatinina <50 ml/min)
9. Storia di malattia epatica scompensata (AST o ALT=5x ULN o ALT = 3 x ULN e bilirubina = 1,5 x ULN con bilirubina diretta >35%), o presenza di ascite, encefalopatia, coagulopatia, ipoalbuminemia, varici esofagee o gastriche
10. Donne in gravidanza o allattamento
11. Qualsiasi valore degli esami ematochimici con tossicità di grado 3/4 in base alla scala di valutazione della Divisione AIDS (DAIDS), ad eccezione di: un incremento di grado 3, asintomatico, di amilasi, CPK o lipidi
12. Qualsiasi condizione (compreso l’uso di droghe illecite o alcool) o valori di laboratorio che, a parere dello sperimentatore, possano interferire con le valutazioni o il completamento dello studio.

E.5 End points

E.5.1

Primary end point(s)

Comparison of the immediate vs delayed group in the % change from baseline in BMD at the
lumbar spine at week 48.

Confronto tra il gruppo di switch immediato vs ritardato nella variazione % di BMD a livello della colonna vertebrale lombare tra il basale e la settimana 48

E.5.1.1

Timepoint(s) of evaluation of this end point

Between baseline and week 48 visit

Tra la visita basale e la settimana 48

E.5.2

Secondary end point(s)

% change from baseline in BMD at lumbar spine at 96 weeks; % change from baseline in BMD at hip at 48 weeks; % change from baseline in BMD at hip at 96 weeks; Changes in Bone architecture as determined by Trabecular bone scan (TBS) and
HRpQCT; Changes in 10 year fracture risk determined by country specific FRAX calculator; % of patient with HIV-1 RNA <50 c/ml; Change from baseline in geriatric functional measures; Change from baseline in muscle quality; Change from baseline in lipid values and Framingham cardiovascular risk scores; Changes in renal tubular and glomerular function; Safety (clinical and laboratory adverse events); Changes in biomarkers of inflammation, coagulation and bone metabolism; Tolerability

variazione in % in BMD a livello lombare dal basale alla settimana 96 ; variazione in % in BMD a livello dell'anca dal basale alla settimana 48; variazione in % in BMD a livello dell'anca dal basale alla settimana 96; Variazioni nell'architettura ossea come determinati dalla scansione osseo trabecolare (TBS) e HRpQCT; Variazioni nel rischio di frattura a 10 anni determinato con un calcolo FRAX paese specifico; % di pazienti con HIV -1 RNA <50 c/ml; Variazioni rispetto al basale delle misurazioni di funzionalit¿ geriatrica; Variazioni rispetto al basale della qualit¿ muscolare; Variazioni rispetto al basale dei valori lipidici e del punteggio del rischio cardiovascolari di Framingham; Variazioni nella funzionalit¿ tubulare e glomerulare; Sicurezza (eventi avversi clinici e di laboratorio); Variazioni dei biomarcatori di infiammazione, coagulazione e metabolismo dell'osso; Tollerabilit¿

E.5.2.1

Timepoint(s) of evaluation of this end point

at 96 week; at 48 week; at week 96; at week 48 and 96; at week 48 and 96; at week 48 and 96; at week 48 and 96; at week 48 and 96; at week 48 and 96; at week 48 and 96; at week 48 and 96; at week 48 and 96; at week 48 and 96

alla 96a settimana; 48a settimana; 96a settimana; 48a e 96a ; 48a e 96a ; 48a e 96a ; 48a e 96a ; 48a e 96a ; 48a e 96a; 48a e 96a ; 48a e 96a ; 48a e 96a ; 48a e 96a settimana

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

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

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

I pazienti saranno randomizzati ad una modifica immediata oppure ritardata della terapia

Patients will be randomised to immediate vs delayed switch

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

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

Information not present in EudraCT

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

Canada

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:

128

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

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

F.3.3.2

Women of child-bearing potential using contraception

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

128

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)

At the end of the study subjects will be followed as per clinical practice

Al termine dello studio i soggetti verranno seguiti secondo normale 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

2018-01-22

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-10-10

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2022-09-26

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