Clinical Trials Register

Summary
EudraCT Number:	2014-003419-12
Sponsor's Protocol Code Number:	SWEAR-1
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2015-01-23
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

2014-003419-12

A.3

Full title of the trial

A Pilot Randomized Controlled Trial of Switch to tenofovir disoproxil
fumarate/emtricitabine/rilpivirine (TDF/FTC/RPV) versus continue
TDF/FTC/efavirenz (EFV) treatment among virologically suppressed, HIV-1
infected subjects with mild or asymptomatic EFV-related neurocognitive or
neuropsychological side effects

Studio pilota randomizzato controllato di switch a tenofovir
disoproxilfumarato/emtricitabina/rilpivirina (TDF/FTC/RPV) versus
prosecuzione di TDF/FTC/efavirenz (EFV) in pazienti HIV-1 positivi,
virologicamente soppressi, con deficit neuro-cognitivo lieve/asintomatico o
con effetti avversi neuropsicologici

A.3.1

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

Switch from Efavirenz/Atripla to Rilpivirine

Switch da Efavirenz/Atripla a Rilpivirina

A.3.2

Name or abbreviated title of the trial where available

SWEAR

A.4.1

Sponsor's protocol code number

SWEAR-1

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 OSPEDALIERA SAN GERARDO, MONZA, ITALIA
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 Srl
B.4.2	Country	Italy
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	AZIENDA OSPEDALIERA SAN GERARDO, MONZA, ITALIA
B.5.2	Functional name of contact point	UFFICIO RICERCA
B.5.3	Address:
B.5.3.1	Street Address	VIA PERGOLESI, 33
B.5.3.2	Town/ city	MONZA
B.5.3.3	Post code	20900
B.5.3.4	Country	Italy
B.5.4	Telephone number	+390392334959
B.5.5	Fax number	+390392334903
B.5.6	E-mail	ufficioricerca@hsgerardo.org

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	EVIPLERA
D.2.1.1.2	Name of the Marketing Authorisation holder	AZIENDA OSPEDALIERA SAN GERARDO, MONZA, ITALIA
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.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
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	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	ATRIPLA
D.2.1.1.2	Name of the Marketing Authorisation holder	GILEAD SCIENCES Srl
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	ATRIPLA
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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

HIV INFECTION

INFEZIONE DA HIV

E.1.1.1

Medical condition in easily understood language

HIV

E.1.1.2

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

MedDRA Classification

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 if the switch from TDF / FTC / EFV to TDF / FTC / RPV is
associated with an improvement in neurocognitive performance or
neuropsychological wellness

Verificare se lo switch da TDF/FTC/EFV a TDF/FTC/RPV sia associato ad
un miglioramento delle performance neurocognitive o del benessere
neuropsicologico

E.2.2

Secondary objectives of the trial

- To evaluate if the switch to TDF / FTC / RPV is associated with a rate of
HIV virologic suppression comparable to that obtained with regimen
containing EFV.
- To evaluate if the switch from TDF / FTC / EFV to TDF / FTC / RPV is
associated with an improvement in fasting lipid parameters.
- To evaluate if the switch from TDF / FTC / EFV to TDF / FTC / RPV is
associated with an improvement in the quality of life perceived by
patients.
- To evaluate if the switch from TDF / FTC / EFV to TDF / FTC / RPV is
associated with an improvement in subjective CNS disorders.
- Measure the proportion of patients who, in the course of a stable
regimen containing EFV, present:
• mild EFV-associated CNS side effects,
• mild or asymptomatic neurocognitive impairment

− Verificare se lo switch a TDF/FTC/RPV si associ a tassi di soppressione
virologica comparabili alla prosecuzione di un regime virologicamente
efficace contente EFV.
− Verificare se lo switch da TDF/FTC/EFV a TDF/FTC/RPV si associ ad un
miglioramento dei parametri lipidici a digiuno.
− Verificare se lo switch da TDF/FTC/EFV a TDF/FTC/RPV si associ ad un
miglioramento della qualità della vita percepita dai pazienti.
− Verificare se lo switch da TDF/FTC/EFV a TDF/FTC/RPV sia associato
ad un miglioramento dei disturbi soggettivi a carico del SNC.
− Misurare la proporzione di pazienti che, in corso di un regime stabile
contente EFV, presentano:
• Effetti collaterali lievi al SNC, associati ad EFV
• Impairment neurocognitivo lieve o asintomatico

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Age greater than 18 years, and ability to provide informed consent
- Treatment with TDF, FTC and EFV for at least 180 days at the time of
screening co-formulated in Atripla®
- HIV-1 RNA <50 copies /ml in two consecutive surveys (including the
detection at screening)
- Adequate linguistic competence for the performance of
neuropsychological tests
- Presence of at least one of the following conditions:
• Altered score in one or more domains in neuropsychological test scores
• Altered score in the test scores of depression, insomnia or anxiety
- Negative pregnancy test (Gravindex) at baseline

− Età maggiore di 18 anni e capacità di firmare il consenso informato
− Trattamento con TDF, FTC ed EFV da almeno 180 giorni, al momento
dello screening co-formulati in Atripla®
− HIV-1 RNA <50 copie/ml in 2 rilevazioni consecutive (inclusa la
rilevazione allo screening)
− Adeguata competenza linguistica per lo svolgimento dei test
neuropsicologici
− Presenza di almeno una delle seguenti condizioni:
• Punteggio alterato in 1 o più domini nel test di valutazione
neuropsicologico
• Punteggio alterato nei test di valutazione della depressione, insonnia o
ansia
- Test di gravidanza negativo (Gravindex) per le donne fertili
all'arruolamento

E.4

Principal exclusion criteria

- History of previous failure to antiretroviral therapy or of mutations
associated with resistance to NRTIs or NNRTIs;
- Treatment, in progress or planned, with proton pump inhibitors or with
other contraindicated medications
- Presence of any contraindication to the use of the study drugs;
- Diagnosis of AIDS in the 30 days prior to screening;
- Prior diagnosis of AIDS Dementia Complex;
- Dependence on alcohol or other substances
- Major psychiatric disorders
- Plasma creatinine> 1.2 mg / dl or glomerular filtration rate <60 ml /
min (MDRD formula)
- AST, ALT, or serum bilirubin> 3 times the upper normal value
- Decompensated cirrhosis
- Any other medical condition or prior therapy that makes the subject
unsuitable for the study or unable to follow the correct dosage or dietary
prescriptions
- Women of childbearing potential not using contraception

− Storia di precedente fallimento alla terapia antiretrovirale o di
mutazioni associate a resistenza agli NRTI o NNRTI;
− Trattamento, in corso o previsto, con inibitori di pompa protonica o
con altri farmaci controindicati
− Presenza di qualsiasi controindicazione all'uso dei farmaci dello studio;
− Diagnosi di AIDS nei 30 giorni precedenti lo screening;
− Pregressa diagnosi di AIDS Dementia Complex;
− Dipendenza da alcol o da altre sostanze
− Disordini psichiatrici maggiori
− Creatinina plasmatica>1.2 mg/dl o filtrato glomerulare < 60 ml/min
(MDRD formula)
− AST, ALT o bilirubina plasmatica > 3 volte il valore superiore normale
− Cirrosi scompensata
− Qualsiasi altra condizione clinica o precedente terapia che renda il
soggetto non idoneo per lo studio o incapace a seguire il corretto
dosaggio o le prescrizioni dietetiche
− Donne in età fertile che non fanno uso di contraccettivi

E.5 End points

E.5.1

Primary end point(s)

- Proportion of patients with an improvement in neurocognitive
performance in one of the investigated domains, evaluated in binary
form (Normal / Abnormal) or on a continuous scale (absolute change in
deficit score)
- Proportion of patients with an improvement in the scores of
depression, anxiety or sleep quality, measured in binary (Yes / No) and
on a continuous scale
- Proportion of patients with an improvement in any of the two previous
binary end-point (composite end point)

− Proporzione di pazienti con un miglioramento nelle performance
neurocognitive in uno dei domini investigati, valutata in forma binaria
(Normale/Anormale) o su una scala continua (variazione assoluta del
punteggio di deficit)
− Proporzione di pazienti con un miglioramento nei punteggi di
depressione, ansia o qualità del sonno, valutati in forma binaria (Si/No)
e su scala continua
− Proporzione di pazienti con un miglioramento in uno qualsiasi dei due
precedenti end-point binari (end-point composito)

E.5.1.1

Timepoint(s) of evaluation of this end point

28 WEEKS

28 SETTIMANE

E.5.2

Secondary end point(s)

- Symptomatic, neuropsychological or neurcognitive end-points
• Variation in scores of quality of life
• Proportion of patients with an improvement in CNS symptoms
• Proportion of patients with an improvement in the CFQ
- Virological end-points
• Proportion of patients with HIV-RNA <50 copies /ml after 12 and 24
weeks of treatment (ITT M = F)
• Proportion of patients with HIV-RNA <400 copies /ml after 12 and 24
weeks (ITT M = F)
• Proportion of patients who develop virologic rebound, defined as two
HIV-RNA> 50 copies /ml results in two consecutive determinations,
distant at least 4 weeks apart
• Number of patients with genotypic resistance at failure
- Immunological end-points
• Modification from baseline of CD4+ and CD8+ T cells at weeks at 12
and 24
- Safety and tolerability end-points
• Proportion of patients who discontinue treatment because of intolerance to study drugs or due to the development of adverse events
• Proportion of patients who develop an adverse event of grade III or IV

− End-point sintomatici, neuropsicologici o neurcognitivi
• Variazione degli score di qualità della vita
• Proporzione di pazienti con un miglioramento dei sintomi a carico del
SNC
• Proporzione di pazienti con un miglioramento nel CFQ
− End-point virologici
• Proporzione di pazienti con HIV-RNA <50 copie/ml dopo 12 e 24
settimane di trattamento (ITT-M=F)
• Proporzione di pazienti con HIV-RNA <400 copie/ml dopo 12 e 24
settimane (ITT-M=F)
• Proporzione di pazienti che sviluppano un rebound virologico, definito
come due HIV-RNA >50 copie/ml in due determinazioni consecutive,
distanti almeno 4 settimane l'una dall'altra
• Numero di pazienti con resistenza genotipica al fallimento
− End-point ImmunologicI
• Modificazione dal baseline dei linfociti T CD4+ e CD8+ alle settimane
12 e 24
− End-point di sicurezza e tollerabilità
• Proporzione dei pazienti che sospendono il trattamento per
intolleranza ai farmaci in studio o per eventi avversi
• Proporzione di pazienti che sviluppano un evento avverso di grado III
o IV

E.5.2.1

Timepoint(s) of evaluation of this end point

28 WEEKS

28 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

Yes

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)

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

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

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

ULTIMA VISITA DELL'ULTIMO SOGGETTO

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

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.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)

BOTH TREATMENT ARE COMMONLY USED IN NORMAL PRACTICE IN THE
TREATMENT OF HIV INFECTION, SO AT THE END OF THE STUDY IS NOT
PROVIDED ANY FURTHER STEP OF ADDITIONAL SURVEILLANCE

ENTRAMBI I TRATTAMENTI SONO UTILIZZATI IN NORMALE PRATICA
CLINICA NELL'INFEZIONE DA HIV E PERTANTO ALLA FINE DELLO
STUDIO NON E' PREVISTA UN UN'ULTERIORE FASE DI VIGILANZA
AGGIUNTIVA

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

2015-04-28

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-06-18

P. End of Trial
P.	End of Trial Status	Ongoing

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