Clinical Trials Register

Summary
EudraCT Number:	2011-005973-21
Sponsor's Protocol Code Number:	RTLP
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:	2012-03-07
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

2011-005973-21

A.3

Full title of the trial

A prospective, randomized, open-label trial of two abacavir/lamivudine based regimen (ABC/3TC + darunavir/ritonavir or ABC/3TC + raltegravir) in late presenter naïve patients (with CD4 count <200 cells/µL - advanced HIV disease)

Studio prospettico, randomizzato, in aperto basato su due regimi contenenti abacavir/lamivudina (abacavir/lamivudina + darunavir/ritonavir o abacavir/lamivudina + raltegravir), in pazienti naive late presenter (con conta dei linfociti CD4 <200cell/ µL -stadio avanzato della malattia da HIV).

A.3.1

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

A.3.2

Name or abbreviated title of the trial where available

RTLP

A.4.1

Sponsor's protocol code number

RTLP

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 POLICLINICO 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	ViiV Healthcare
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	Universita' degli Studi di Modena e Reggio Emilia
B.5.2	Functional name of contact point	Clinica Malattie Infettive
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	+39 059 422 3673
B.5.5	Fax number	+39 059 422 2604
B.5.6	E-mail	nb.protocolli@unimore.it

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	KIVEXA*FL 30CPR RIV 600MG+300M
D.2.1.1.2	Name of the Marketing Authorisation holder	VIIV HEALTHCARE 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.3.4	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	ABACAVIR SULFATE
D.3.9.1	CAS number	188062-50-2
D.3.9.4	EV Substance Code	SUB00231MIG
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.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	LAMIVUDINE
D.3.9.1	CAS number	134678-17-4
D.3.9.4	EV Substance Code	SUB08392MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/g milligram(s)/gram
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	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	ISENTRESS*FL 60CPR RIV 400MG
D.2.1.1.2	Name of the Marketing Authorisation holder	MERCK SHARP & DOHME SpA
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.3.4	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	RALTEGRAVIR POTASSIUM
D.3.9.1	CAS number	871038-72-1
D.3.9.4	EV Substance Code	SUB25668
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	400
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: 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	PREZISTA*60CPR RIV 400MG
D.2.1.1.2	Name of the Marketing Authorisation holder	JANSSEN CILAG SpA
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.3.4	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	DARUNAVIR ETHANOLATE
D.3.9.1	CAS number	635728-49-3
D.3.9.4	EV Substance Code	SUB23573
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	400
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: 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	NORVIR*FL 30CPR RIV 100MG
D.2.1.1.2	Name of the Marketing Authorisation holder	ABBOTT 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.3.4	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	RITONAVIR
D.3.9.1	CAS number	155213-67-5
D.3.9.4	EV Substance Code	SUB10342MIG
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	100
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Advanced HIV disease, defined as a CD4 cell count <200 cells/µL or the presence of an AIDS-defining event.

Malattia da HIV in stadio avanzato (conta delle cellule CD4 <200 cell/mL o presenza di un evento definente AIDS).

E.1.1.1

Medical condition in easily understood language

Advanced HIV disease, defined as a CD4 cell count <200 cells/µL or the presence of an AIDS-defining event.

Malattia da HIV in stadio avanzato (conta delle cellule CD4 <200 cell/mL o presenza di un evento definente AIDS).

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	14.1
E.1.2	Level	PT
E.1.2	Classification code	10020161
E.1.2	Term	HIV infection
E.1.2	System Organ Class	10021881 - Infections and infestations

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Proportion of patients with undetectable viremia (HIV-1 RNA<50 copies/mL) after 48 weeks

Confrontare la risposta virologica a 48 settimane di due differenti regimi contenenti abacavir/lamivudina (ABC/3TC) (ABC/3TC + darunavir/ritonavir (DRV/r) vs ABC/3TC + raltegravir (RAL)) in soggetti con infezione da HIV, naive alla terapia antiretrovirale e conta dei linfociti CD4 <200cell/ µL.

E.2.2

Secondary objectives of the trial

Change in CD4+ cell count from baseline through week 48; Time to virological rebound, defined as plasma HIV RNA >50 copies/mL measured on two consecutive occasions at least one month apart.

Confrontare la risposta immunologica a 48 settimane Determinare la sicurezza e la tollerabilità dei due regimi

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Males or females aged 18-64 years who are HIV-1 antibody seropositive, with a CD4 count <200 cells/uL. 2. All patients should be antiretroviral-naive 3. All patients should be HLA B57 or HLA B5701 negative 4. Patients must have an HIV RNA level <500,000 copies/mL 5. Patients with an active opportunistic infection could be enrolled as long as this was diagnosed more than 2 weeks prior to screening. 6. Patients must meet the following laboratory criteria. Neutrophil count  1,000 cells/mm3 Haemoglobin > 9.0 grams/dl (men and women) Platelet count ≥ 75,000 cells/mm3 Alkaline phosphatase < 3.0 the upper limit of normal ALT and AST < 3.9 times the upper limit of normal Total bilirubin < 1.5 times the upper limit of normal. 7. Female patients of childbearing potential must be willing to use a reliable form of contraception, which will include a medically approved form of barrier contraception. 8. Patients must be able to provide written consent to comply with study requirements.

 Uomini e donne con età compresa tra 18 e 64 anni  Sieropositività per HIV  Conta dei linfociti CD4 <200cell/ µL  Tutti i soggetti non devono avere mai assunto farmaci antiretrovirali  Test HLA B5701, o HLA B57, negativo  Carica virale per HIV-RNA < 500.000 copie/ml  I soggetti possono avere un’infezione opportunistica in atto, purché sia stata diagnosticata più di 2 settimane prima della visita di screening  Presenza dei seguenti parametri di laboratorio - Conta dei neutrofili >1000 cell/mm3 - emoglobina >9.0 g/dl - piastrine ≥ 75.000 cell/ mm3 - fosfatasi alcalina <3 volte il limite maggiore di normalità - ALT e AST < 3.9 volte il limite maggiore di normalità - Bilirubina totale < 1.5 volte il limite maggiore di normalità  Donne potenzialmente fertili devono acconsentire ad utilizzare un metodo contraccettivo sicuro, che includa un metodo a barriera  I soggetti devono essere in grado di fornire un consenso informato scritto e rispettare le procedure dello studio

E.4

Principal exclusion criteria

1. Patients with genotypic mutations for any of the study drugs. 2. Patients with an opportunistic infection diagnosed in the 2 weeks prior to screening. 3. Female patients who are pregnant or breastfeeding. 4. Patients who are receiving any investigational drug or anti-neoplastic radiotherapy/chemotherapy other than local skin radiotherapy within 12 weeks before randomization. 5. Patients with a current history of intravenous drug abuse, alcohol or substance abuse.

 Test genotipico che presenti resistenze ai farmaci antiretrovirali in studio  Donne in gravidanza o in allattamento  Soggetti che stiano assumendo qualsiasi farmaco sperimentale o radioterapia/chemioterapia anti-tumorale ad eccezione della radioterapia cutanea locale, entro 12 settimane dallo screening  Soggetti con dipendenza attiva da droghe per via endovenosa, alcool o altre sostanze tossiche.

E.5 End points

E.5.1

Primary end point(s)

Proportion of patients with undetectable viremia (HIV-1 RNA<50 copies/mL) after 48 weeks

E.5.1.1

Timepoint(s) of evaluation of this end point

48 weeks

48 settimane

E.5.2

Secondary end point(s)

Time to virological rebound, defined as plasma HIV RNA >50 copies/mL measured on two consecutive occasions at least one month apart.

Confrontare la risposta immunologica a 48 settimane Determinare la sicurezza e la tollerabilità dei due regimi

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

Yes

E.6.4

Safety

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)

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

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

Number of subjects for this age range:

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:

350

F.1.3

Elderly (>=65 years)

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

350

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)

Usual care practise

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

2013-11-20

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-03-06

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

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