Clinical Trials Register

Summary
EudraCT Number:	2014-002471-28
Sponsor's Protocol Code Number:	TMC278IFD3004
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Trial now transitioned
Date on which this record was first entered in the EudraCT database:	2021-01-21
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

2014-002471-28

A.3

Full title of the trial

An open-label, roll-over study with rilpivirine in combination with a background regimen containing antiretrovirals (ARVs) in human immunodeficiency virus type 1 (HIV-1) infected subjects who participated in rilpivirine pediatric studies

Studio di rollover in aperto con rilpivirina in combinazione con un regime di base contenente altri antiretrovirali (ARV) in soggetti affetti dal virus dell’immunodeficienza umana di tipo 1 (HIV-1), che hanno partecipato a studi pediatrici su rilpivirina

A.3.1

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

A roll-over study with rilpivirine for human immunodeficiency virus type 1 (HIV-1) infected subjects who participated in rilpivirine pediatric studies

Studio di rollover con rilpivirina in soggetti affetti dal virus dell’immunodeficienza umana di tipo 1 (HIV-1) che hanno partecipato a studi pediatrici su rilpivirina

A.3.2

Name or abbreviated title of the trial where available

TMC278IFD3004

A.4.1

Sponsor's protocol code number

TMC278IFD3004

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT02494986

A.5.4

Other Identifiers

Name:

Unique Protocol ID

Number:

CR107451

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/205/2019

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Janssen Sciences Ireland Unlimited Company
B.1.3.4	Country	Ireland
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Janssen Sciences Ireland UC
B.4.2	Country	Ireland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Janssen-Cilag International NV
B.5.2	Functional name of contact point	Clinical Registry Group
B.5.3	Address:
B.5.3.1	Street Address	Archimedesweg 29
B.5.3.2	Town/ city	Leiden
B.5.3.3	Post code	2333 CM
B.5.3.4	Country	Netherlands
B.5.4	Telephone number	3100715242166
B.5.5	Fax number	3100715242110
B.5.6	E-mail	ClinicalTrialsEU@jnj.its.com

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	EDURANT - 25 MG - COMPRESSA RIVESTITA CON FILM - USO ORALE - FLACONE (HDPE) 30 COMPRESSE
D.2.1.1.2	Name of the Marketing Authorisation holder	JANSSEN-CILAG INTERNATIONAL N.V.
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	Edurant® (rilpivirine) 25mg tablets
D.3.2	Product code	[TMC278/GFI-314585-CA-026]
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.3.9.1	CAS number	700361-47-3
D.3.9.2	Current sponsor code	TMC278
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.3.11 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	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	No
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	Rilpivirine Hydrochloride
D.3.2	Product code	[TMC278 (G009-01)]
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	Yes
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 hydrochloride
D.3.9.1	CAS number	700361-47-3
D.3.9.2	Current sponsor code	TMC278 (G009-01)
D.3.9.4	EV Substance Code	SUB31460
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	2500
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-1 Infection

Infezione da HIV-1

E.1.1.1

Medical condition in easily understood language

HIV-1 Infection

Infezione da HIV-1

E.1.1.2

Therapeutic area

Diseases [C] - Virus Diseases [C02]

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

The primary objective is to provide continued access to RPV for subjects who were treated with RPV in a clinical development pediatric study with rilpivirine and who, at the time of roll-over, experience and are expected to continue experiencing clinical benefit from RPV treatment

L’obiettivo primario di questo studio è fornire accesso continuo a RPV ai soggetti che sono stati trattati con RPV in uno studio pediatrico di sviluppo clinico di RPV e che, al momento del rollover, traggono e si prevede che continuino a trarre beneficio clinico dal trattamento con RPV

E.2.2

Secondary objectives of the trial

The major secondary objective is to evaluate the long-term safety and tolerability of RPV in combination with a background regimen containing other ARVs. Another secondary objective is to evaluate available efficacy data, including HIV-1 resistance data in case of virologic failure.

L’obiettivo secondario principale è valutare la sicurezza e la tollerabilità a lungo termine di RPV in combinazione con un regime di base contenente altri antiretrovirali (ARV).Un altro obiettivo secondario è valutare i dati di efficacia disponibili, inclusi quelli relativi alla resistenza dell’HIV-1 in caso di insufficienza virologica.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Each potential subject must satisfy all of the following criteria to be enrolled in the study.
1. Subjects (or their legally acceptable representative) must sign an Informed Consent Form (ICF) indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study. Assent is also required of children capable of understanding the nature of the study (typically 7 years of age and older).
2. Subjects must be HIV-1 infected and must have previously been treated with RPV 25 mg qd (or weight-adjusted dose) in a clinical development pediatric study and completed the protocol-defined treatment period.
3. Subjects must benefit from treatment with RPV, according to the efficacy and safety criteria as set out in the protocol of the pediatric study with RPV the subject was participating in prior to this rollover study, and must be expected to continue to benefit from this treatment in the opinion of the investigator.
4. Subjects must be able and willing to comply with the current protocol requirements.
5. Subjects’ general medical condition, in the opinion of the investigator, does not interfere with participation in this study.

Ogni potenziale soggetto deve soddisfare tutti i seguenti criteri per essere arruolato nello studio.
1. I soggetti (o i loro rappresentanti legali) devono firmare un Modulo di Consenso Informato (ICF) nel quale indicano di aver compreso lo scopo e le procedure necessarie per lo studio e che sono disposti a parteciparvi. L’assenso è necessario anche per i bambini in grado di comprendere la natura dello studio (in genere di età pari o superiore a 7 anni) come descritto nella Sezione 16.2.3. del protocollo di studio.
2. I soggetti devono essere affetti da HIV-1 e devono essere stati precedentemente trattati con RPV 25 mg qd (o con una dose adeguata al peso) in uno studio pediatrico di sviluppo clinico e devono aver completato il periodo di trattamento definito dal protocollo.
3. I soggetti devono trarre beneficio dal trattamento con RPV, in base ai criteri di efficacia e sicurezza descritti nel protocollo dello studio pediatrico con RPV a cui hanno partecipato prima di questo studio di rollover e deve essere plausibile che continuino a trarre beneficio da questo trattamento a giudizio dello sperimentatore.
4. I soggetti devono essere in grado e disposti ad attenersi ai requisiti del protocollo attuale.
5. La condizione clinica generale dei soggetti, a giudizio dello sperimentatore, non interferisce con la partecipazione a questo studio.

E.4

Principal exclusion criteria

Any potential subject who meets any of the following criteria will be excluded from participating in the study.
1. Subjects using disallowed concomitant treatment.
2. Pregnant subjects.
3. Female subjects of childbearing potential and non-vasectomized heterosexually active male subjects not willing to continue practicing birth control methods during the study and for =1 month after the end of the study (or after last intake of RPV). Effective birth control methods are:
a. male condom* in combination with diaphragm or cervical cap**;
b. intrauterine device or hormonal contraceptive in combination with a barrier contraceptive (ie, male or female condom*, diaphragm, or cervical cap**);
c. practice sexual abstinence, or have no heterosexual interaction, or have a vasectomized
partner (vasectomy should have been performed >1 month prior to withdrawal of these other effective birth control methods).
* A male and female condom should not be used together due to risk of breakage or damage caused by latex friction.
** A cervical cap has been shown to be less effective in parous women. Therefore, this barrier method is preferably not used in parous women in this trial.
Note: Spermicides should not be used as this can potentially increase the rate of HIV-1 transmission.20
4. Subjects who were withdrawn from a pediatric study with RPV that they were participating in prior to this rollover study, based on any of the mandatory withdrawal criteria.
NOTE: Investigators should ensure that all study enrollment criteria have been met at the Roll-over Visit.

Tutti i potenziali soggetti che soddisfano uno qualsiasi dei seguenti criteri saranno esclusi dalla partecipazione allo studio.
1. Soggetti che utilizzano trattamenti concomitanti non consentiti (vedere Sezione 8 del protocollo di studio).
2. Soggetti in stato di gravidanza.
3. Soggetti di sesso femminile potenzialmente fertili e soggetti di sesso maschile non vasectomizzati etero sessualmente attivi non disposti a continuare ad adottare metodi contraccettivi durante lo studio e per =1 mese dopo la fine dello studio (o dopo l’ultima assunzione di RPV). I metodi contraccettivi efficaci sono:
a. preservativo maschile* associato a diaframma o cappuccio cervicale**;
b. dispositivo intrauterino o contraccettivo ormonale in combinazione con un contraccettivo a barriera (ovvero, preservativo maschile o femminile*, diaframma o cappuccio cervicale**);
c. pratica dell’astinenza sessuale o non avere alcun rapporto eterosessuale o avere un compagno vasectomizzato (la vasectomia deve essere stata eseguita >1 mese prima della sospensione di questi altri metodi contraccettivi efficaci).
* L’uso concomitante di preservativo maschile e femminile deve essere evitato a causa del rischio di rottura o danno causato dalla frizione del lattice.
** Il cappuccio cervicale ha dimostrato di essere meno efficace in donne che hanno avuto più di un figlio Pertanto, è preferibile non utilizzare questo metodo barriera nelle donne con figli che partecipano a questa sperimentazione.
Nota: Gli spermicidi non devono essere utilizzati in quanto è possibile che facciano aumentare il tasso di trasmissione dell’HIV-1.
4. I soggetti che sono stati ritirati da uno studio pediatrico con RPV a cui partecipavano prima di questo studio di rollover, sulla base di uno qualsiasi dei criteri di interruzione obbligatori.

E.5 End points

E.5.1

Primary end point(s)

No primary endpoint is defined for this study

In considerazione dell’obiettivo primario dello studio, atto a fornire accesso continuo a RPV, non è stato definito alcun endpoint primario per questo studio.

E.5.1.1

Timepoint(s) of evaluation of this end point

Not applicable

non applicabile

E.5.2

Secondary end point(s)

The proportion of subjects experiencing adverse events (AEs) considered to be at least possibly related to RPV, AEs leading to discontinuation, serious AEs (SAEs), pregnancies, and grade 3/4 rash regardless of causality throughout the study. Results of routine safety laboratory tests will only be collected if related to these types of AEs.; The proportion of subjects maintaining viral suppression (ie, <50 HIV-1 RNA copies/mL) based on available viral load data throughout the study. In case of virologic failure, emergence of resistance will also be evaluated based on available genotype/phenotype data.

Percentuale di soggetti che manifestano eventi avversi (AE) considerati almeno probabilmente correlati a RPV, AE che portano all’interruzione del trattamento, eventi avversi seri (SAE), gravidanze ed eruzioni cutanee di grado 3/4, a prescindere dalla causalità per tutta la durata dello studio. I risultati degli esami di laboratorio di routine di sicurezza saranno raccolti solo se correlati a questi tipi di AE; Percentuale di soggetti che mantengono la soppressione virale (vale a dire <50 copie/ml di HIV-1 RNA) sulla base dei dati sulla carica virale disponibili per tutta la durata dello studio. In caso di fallimento virologico, sarà inoltre valutata la comparsa di resistenza sulla base dei dati sul genotipo/fenotipo disponibili.

E.5.2.1

Timepoint(s) of evaluation of this end point

Throughout the study; Throughout the study

tutta la durata dello studio; tutta la durata dello studio

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

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

Yes

E.6.13.1

Other scope of the trial description

Tolerability and Roll-over study

Tolletabilità e studio di Roll-over

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)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

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

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

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

Kenya

South Africa

Thailand

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

The study is considered completed when all subjects have switched to one of the following options, as appropriate for the subject’s age: (1) locally available RPV (ie, commercially available AND reimbursed, OR accessible through another source [eg, access program or government program]), (2) other local RPV-based regimens, or (3) local standard of care

LVLS
Lo studio è considerato completato quando tutti i soggetti sono passati a una delle seguenti opzioni, a seconda dell'età del soggetto: (1) RPV disponibile localmente (ovvero, disponibile in commercio E rimborsato, O accessibile tramite un'altra fonte [ad esempio, programma di accesso o governo programma]), (2) altri regimi locali basati su RPV o (3) standard di cura locali

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

Yes

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)

Yes

F.1.1.5.1

Number of subjects for this age range:

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

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

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

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Children (minors) or subjects who are unable to comprehend the information provided can be enrolled only after obtaining consent of a legally acceptable representative

Bambini (minori) o soggetti che non sono in grado di comprendere le informazioni fornite possono essere arruolati solo dopo aver ottenuto il consenso di un rappresentante legalmente accettabile

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

100

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)

Standard of care

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

2020-09-04

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-07-29

P. End of Trial
P.	End of Trial Status	Trial now transitioned

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