Clinical Trials Register

Summary
EudraCT Number:	2014-004297-42
Sponsor's Protocol Code Number:	IN-NL-2641449
National Competent Authority:	Netherlands - Competent Authority
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2015-03-12
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Netherlands - Competent Authority

A.2

EudraCT number

2014-004297-42

A.3

Full title of the trial

Effect of Switching Atripla to Eviplera on neurocognitive and emotional functioning

Effect van switchen van Atripla naar Eviplera op neurocognitief en emotioneel functioneren

A.3.1

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

Effect of changing one medication (Atripla) to another (Eviplera) on functions of the brain and emotions

Het effect van wisselen van het ene medicijn (Atripla) naar het andere medicijn (Eviplera) op de functies van de hersenen en emoties

A.3.2

Name or abbreviated title of the trial where available

ESCAPE

A.4.1

Sponsor's protocol code number

IN-NL-2641449

A.5.4

Other Identifiers

Name:

clinicaltrials.gov

Number:

NCT02308332

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	UMC Utrecht
B.1.3.4	Country	Netherlands
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	Netherlands
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	UMC Utrecht
B.5.2	Functional name of contact point	afdeling infectieziekten
B.5.3	Address:
B.5.3.1	Street Address	Heidelberglaan 100
B.5.3.2	Town/ city	Utrecht
B.5.3.3	Post code	3584 CX
B.5.3.4	Country	Netherlands
B.5.4	Telephone number	0031887555555

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	Gilead Sciences
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.3.4	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	rilpivirine
D.3.9.1	CAS number	700361-47-3
D.3.9.3	Other descriptive name	RILPIVIRINE HYDROCHLORIDE
D.3.9.4	EV Substance Code	SUB31460
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.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Tenofovir
D.3.9.3	Other descriptive name	TENOFOVIR DISOPROXIL
D.3.9.4	EV Substance Code	SUB20643
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	EMTRICITABINE
D.3.9.1	CAS number	143491-57-0
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.3.11 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	Yes
D.3.11.13.1	Other medicinal product type	Eviplera is a fixed-dose combination tablet containing two nucleoside reverse transcriptase inhibitors (emtricitabin, tenofovir) and one non-nucleoside reverse transcriptase inhibitor (Rilpivirine)
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
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.3.4	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	EMTRICITABINE
D.3.9.1	CAS number	143491-57-0
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
D.3.9.3	Other descriptive name	TENOFOVIR DISOPROXIL
D.3.9.4	EV Substance Code	SUB20643
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	efavirenz
D.3.9.3	Other descriptive name	EFAVIRENZ
D.3.9.4	EV Substance Code	SUB06463MIG
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	600
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	Yes
D.3.11.13.1	Other medicinal product type	Atripla is a fixed-dose combination tablet containing two nucleosid transcriptase inhibitors (emtricitabine and tenofovir) and one non-nucleosid transcriptase inhibitor (efavirenz)

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

neurocognitive and emotional functioning in HIV positive men using antiretroviral therapy

neurocognitief en emotioneel functioneren bij HIV positieve mannen die antiretrovirale therapie gebruiken

E.1.1.1

Medical condition in easily understood language

brain functions and emotions with people infected with HIV who use anti-HIV medication.

functies van het brein en emoties bij mensen geïnfecteerd met HIV die anti-HIV medicijnen gebruiken.

E.1.1.2

Therapeutic area

Not possible to specify

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

This study aims to investigate the effect of switching from Atripla to Eviplera on neurocognitive performances (neurocognitive testing) and imaging (functional MRI scanning) in virologically suppressed HIV-infected patients.

De studie wil het effect onderzoeken van switchen van Atripla naar Eviplera op neurocognitief functioneren (neuropsychologisch onderzoek) en beeldvorming (functionele MRI) in virologisch onderdrukte HIV-geïnfecteerde patiënten

E.2.2

Secondary objectives of the trial

not applicable

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Male, between 30 and 50 years
- HIV-1 RNA < 50 copies/mL on last routine measurement during outpatient clinic
- on EFV/FTC/TDF STR (Atripla) continuously for ≥6 months preceding the screening visit
- Have a HIV genotype prior to starting cART with EFV/FTC/TDF STR with no known resistance to any of the study agents at any time in the past including, but not limited to RT mutations K65R, K101E/P, E138G/K/Q/R, Y181C/I/V, M184V/I and H221Y
- Negative TPHA or VDRL < 12 months prior to or at the screening visit
- no signs of an acute or chronic hepatitis C infection within the past 12 months before screening as defined in the Dutch guideline (Arends et al. Neth J Med 2011)
- No subjective neurocognitive complaints in the preceding 12 months
- willingness to take Eviplera together with food according to the manufacturer’s prescriptions.
- Estimated glomerular filtration rate ≥50 mL/min (Cockcroft-Gault formula) on last routine measurement during outpatient clinic
- able to understand and comply to study procedures and to provide written informed consent

- mannelijk, tussen 30 en 50 jaar
- HIV-1 RNA < 50 kopieën/mL bij laatste routinemeting bij polibezoek
- op EFV/FTC/TDF STR (Atripla) voor ≥6 maanden voorafgaand aan, of tijdens screening
- hebben van een HIV genotype voorafgaand aan start cART met EFV/FTC/TDF STR zonder bekende resistenties voor een van de studie-middelen inclusief, maar niet beperkt tot RT mutaties K65R, K101E/P, E138G/K/Q/R, Y181C/I/V, M184V/I and H221Y
- negatieve TPHA of VDRL < 12 maanden voor screening
- geen tekenen van acute of chronische hepatitis C infectie in de 12 maanden voorafgaand aan screening zoals gedefineerd in de Nederlandse richtlijn
- geen subjectieve neurologische klachten in de voorgaande 12 maanden
- bereid zijn Eviplera met voedsel te nemen volgens de aanwijzingen van de fabrikant
- EGFR ≥50 mL/min (Cockcroft-Gault formule) bij laatste routinemeting bij polibezoek
- in staat zijn de studie werkwijzen te begrijpen en volgen en om geschreven informed consent te kunnen geven

E.4

Principal exclusion criteria

- Insufficient fluency in written and spoken Dutch
- Proven major depression through psychiatric consultation within the past year or on anti-depressant drugs (SSRI or TCA)
- Active or known from medical history past CNS opportunistic infections
- History of proven neurologic disease (e.g. multiple sclerosis, brain tumor, cerebrovasculair event, etc)
- Active psychiatric disorders classified according to the DSM V criteria
- History or evidence of alcohol or drug abuse defined according to DSM V criteria
- TSH not within normal reference values on last routine measurement during outpatient clinic
- Contraindications for undergoing an MRI; a pacemaker or metallic devices/foreign bodies in situ, proven claustrophobia.

- Nederlands niet voldoende beheersen in woord en geschrift
- bewezen ernstige depressie door psychiatrisch onderzoek in het afgelopen jaar, of gebruik van anti-depressiva (SSRI of TCA)
- CZS opportunistische infectie, actief of in de voorgeschiedenis
- bekend met een bewezen neurologische aandoening (e.g. multipele sclerose, hersentumor, CVA, etc)
- actieve psychiatrische stoornis geclassificeerd volgens de DSM V criteria
- Bekend met of bewijs voor alcohol of drugs abusus gedefinieerd volgens de DSM V criteria
- TSH niet binnen normale referentiewaarden bij laatste routinemeting bij polibezoek
- contra-indicaties voor het krijgen van een MRI, een pacemaker of metaal object/corpus alienum in situ, bewezen claustrofobie

E.5 End points

E.5.1

Primary end point(s)

To evaluate the neurocognitive performance (NP composite score) after 12 weeks in stable HIV-infected patients switched from Atripla to Eviplera compared to a control group of patients on Atripla.

Het evalueren van het neurocognitief functioneren (neuropsychologisch onderzoek totale score) na 12 weken in stabiele HIV-geïnfecteerde patiënten die geswitched zijn van Atripla naar Eviplera vergeleken met een controle groep van patiënten op Atripla.

E.5.1.1

Timepoint(s) of evaluation of this end point

12 weeks

12 weken

E.5.2

Secondary end point(s)

1) To assess functional imaging measured by fMRI after twelve weeks of Eviplera compared to a control group of patients on Atripla 2) To assess the correlation between neurocognition as measured by NP composite score and functional imaging as measured by fMRI after switching Atripla to Eviplera 3) to assess health related quality of life (SF-36 total score) after switching from Atripla to Eviplera. 3) to assess the emotional functioning (HADS total score), and participating (USER-P total score) after switching Atripla to Eviplera. 5) to assess drug levels of Efavirenz and Rilpivirin in relation to changes in neurocognitive performance and fMRI in both patient groups.6) to evaluate the usefulness of PROMIS instruments in HIV research.

1) het vaststellen van functionele beeldvorming gemeten door fMRI op twaalf weken na switchen naar Eviplera 2) het beoordelen van de correlatie tussen neurocognitieve verandering (neuropsychologisch onderzoek) en functionele beeldvorming (fMRI) na het switchen van Atripla naar Eviplera. 3) het vaststellen van de gezondheidsgerelateerde kwaliteit van leven (SF-36 totale score) na het switchen van Atripla naar Eviplera. 4) het beoordelen van het emotioneel functioneren (HADS totale score) en de participatie (USER-P total score) na switchen van Atripla naar Eviplera. 5) het beoordelen van medicatiespiegels in relatie tot de veranderingen in neurocognitief functioneren en fMRI in beide patientengroepen. 6) het evalueren van de nuttigheid van PROMIS instrumenten bij HIV patiënten

E.5.2.1

Timepoint(s) of evaluation of this end point

12 weeks

12 weken

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

neurocognition of HIV-patients using antiretroviral therapy is being evaluated. We will use a switch to an antiretroviral medication which has proven less neurological side effects to evaluate neurocognition in HIV patients.

neurocognitie bij HIV patiënten die antiretrovirale medicatie gebruiken wordt onderzocht. Dit doen we door patiënten te switchen naar een medicijn wat bewezen minder neurologische bijwerkingen heeft. Zo kunnen we het verschil beoordelen.

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

Yes

E.8.1.4

Double blind

E.8.1.5

Parallel group

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.8.5

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

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)

F.2 Gender

F.2.1

Female

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

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.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)

Patients who leave the study or are withdrawn from the study will be given the choice to either continue on Eviplera or switch back to their original regimen of Atripla in consultation with their treating physician. They will receive an appointment for further continuation of their follow-up with their own physician.

Patiënten die klaar zijn met de studie of die uitvallen tijdens de studie zullen de keuze krijgen om danwel door te gaan met Eviplera, danwel met hun originele regime met Atripla in samenspraak met hun behandelend arts. Zij zullen een afspraak krijgen om de follow-up met hun behandelend arts te vervolgen.

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

2015-03-12

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-06-15

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

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials