Clinical Trials Register

Summary
EudraCT Number:	2011-003593-85
Sponsor's Protocol Code Number:	VX-950HPC3005
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:	2012-01-13
Trial results	View 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

2011-003593-85

A.3

Full title of the trial

Multicenter, Open-Label, Study of Telaprevir in Combination With Peginterferon Alfa and Ribavirin in Human Immunodeficiency Virus/Genotype 1 Chronic Hepatitis C Coinfected Subjects With Severe Fibrosis or Compensated Cirrhosis

Studio multicentrico, in aperto di Telaprevir in combinazione con Peginterferone Alfa e Ribavirina in soggetti co-infetti da virus della immunodeficienza umana/epatite C cronica di genotipo 1 con fibrosi grave o cirrosi compensata

A.3.1

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

Telaprevir Open-Label Study in Co-Infected Patients

Studio in aperto con Telaprevir in pazienti co-infetti

A.4.1

Sponsor's protocol code number

VX-950HPC3005

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	JANSSEN-CILAG INTERNATIONAL N.V.
B.1.3.4	Country	Belgium
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-Cilag SpA
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	Janssen-Cilag International NV- Clinical Register Group
B.5.2	Functional name of contact point	Janssen Biologics BV
B.5.3	Address:
B.5.3.1	Street Address	Archimedesweg
B.5.3.2	Town/ city	Leiden
B.5.3.3	Post code	2333CM
B.5.3.4	Country	Netherlands
B.5.4	Telephone number	+31 0715242166
B.5.5	Fax number	+31 0715242110
B.5.6	E-mail	ClinicalTrialsEU@its.jnj.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	INCIVO
D.2.1.1.2	Name of the Marketing Authorisation holder	JANSSEN CILAG INTERNATIONAL NV
D.2.1.2	Country which granted the Marketing Authorisation	Belgium
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.3.9.1	CAS number	402957-28-2
D.3.9.2	Current sponsor code	VX-950
D.3.9.3	Other descriptive name	TELAPREVIR
D.3.9.4	EV Substance Code	SUB31651
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	375
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

Chronic Hepatitis C infection

Infezione cronica epatite C

E.1.1.1

Medical condition in easily understood language

Chronic Hepatitis C infection

Infezione cronica epatite C

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	LLT
E.1.2	Classification code	10047457
E.1.2	Term	Viral hepatitis C
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

The objective of this open-label safety study is to collect safety and tolerability data on telaprevir treatment in combination with Peg-IFNalfa and RBV in subjects with HIV/genotype 1 chronic HCV coinfection with severe fibrosis or compensated cirrhosis who are not eligible for enrollment into an ongoing clinical study of telaprevir.

L'obiettivo di questo studio in aperto è quello di raccogliere ulteriori dati di sicurezza e tollerabilità sul trattamento con Telaprevir in combinazione con Peg IFN alfa e RBV in soggetti affetti da co-infezione HIV/epatite C cronica di genotipo 1 con fibrosi grave o cirrosi compensata che non sono idonei all’arruolamento in uno studio clinico di Telaprevir attualmente in corso.

E.2.2

Secondary objectives of the trial

NAP

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Be a man or woman, between 18 and 70 years of age, inclusive,Have diagnosis of HIV-1 or HIV-2 infection, or HIV-1 and HIV-2 coinfection for more than 6 months before the screening visit. Should have been on a stable permissible HAART regimen for more than 8 weeks before Day 1 without switches. If on stable permissible HAART regimen, have CD4 count ≥200 cells/mm3 or ≥15% and HIV-1 and/or HIV-2 viral load <50 copies/mL for at least 6 months before starting treatment is recommended Have evidence of HCV infection genotype 1. Have a quantifiable plasma HCV RNA Have documentation of severe fibrosis (Metavir F3 or Ishak 3-4) or cirrhosis (Metavir F4 or Ishak 5 6) assessed by liver biopsy or non-invasive test (eg, fibrotest, fibroscan)within 18 months before screening. Have compensated liver disease (Child-Pugh Grade A clinical classification) Have access to the hepatitis C treatments Peg-IFN-alfa and RBV Have laboratory values (assessed at local laboratory) that meet the following or adhere to local prescribing information or standard of care:•Absolute neutrophil count (ANC) ≥1,500 cells/mm3;•Platelet count ≥90,000 cells/mm3,•Hemoglobin concentration ≥12 g/dL in females or ≥13 g/dL in males •Calculated creatinine clearance ≥70 mL/min;•Potassium ≥3.5 mmol/L If a women of childbearing potential, must have a negative serum  human chorionic gonadotropin ( hCG) or urine pregnancy test documented at the screening visit and a negative serum or urine pregnancy test before the first dose of study drug to ensure that they are not pregnant at the time of starting treatment.If heterosexually active, a female subject of childbearing potential and a nonvasectomized male subject who has a female partner of childbearing potential must agree to use 2 effective contraceptives from screening onwards until 4 months (female subject) or 7 months (male subject) after RBV therapy has ended. To be eligible for this early access program, subjects should agree to use 2 effective non-hormonal methods of contraception during combination therapy and for 2 months after the last intake of telaprevir; 13. Sign the informed consent document indicating that they understand the purpose of and procedures required for the early access program and are willing to participate in the early access program14.Sign the informed consent form for pharmacogenomic research in order to participate in the optional pharmacogenomic component of this early access program (where local regulations permit). Refusal to give consent for this component does not exclude a subject from participation in the EAP

uomini e donne di età compresa fra i 18 ed i 70 anni di età, inclusi. Infezione da HIV-1 o HIV-2 o coinfetti HIV-1 e HIV-2 per più di 6 mesi dalla visita di screening. In regime stabile terapia HAART per più di 8 sett antecedenti il giorno 1 senza passaggi. Se in regime HAART stabile avere conta CD4>=200cells/mm3 o >=15% e una carica virale HIV-1 e/o HIV-2 <50copie/ml almeno 6 mesi prima dell'inizio trattamento. Infezione da HCV, genotipo 1. Livello quantificabile di HCV RNA nel siero. Documentazione di fibrosi epatica valutata tramite biopsia epatica o test non invasivo (ad es. fibrotest, fibroscan) che mostra fibrosi grave (Metavir F3 o Ishak 3-4) o cirrosi (Metavir F4 o Ishak 5-6). Per i soggetti con Metavir F3 o Ishak 3-4, la biopsia epatica o il test non invasivo dovrebbero essere stati eseguiti entro i precedenti 18 mesi. Presenza di malattia epatica compensata (Child Pugh di grado A). I soggetti devono avere accesso allo standard di cura per l’epatite C (Peg IFN-alfa/RBV). Avere i seguenti valori di laboratorio che incontrano i seguenti requisiti: conta assoluta neutrofila (ANC)>=1500 cells/mm3; conta piastrinica >=90000 cells/mm3; concentrazione emoglobina >=12g/dl femmine e >=13g/dl nei maschi; clearance creatinina >=70ml/min; potassio >=3.5mmol/l. Per le donne in età fertile test negativo di gravidanza su serio (β-HCG) e urine allo screening e prima della prima dose di trattamento per assicurare che le donne non siano incinte al momento di iniziare il trattamento. I soggetti femmine in età fertile e i maschi di partner femminili in età fertile dovranno acconsentire all'uso di 2 metodi contraccettivi efficaci dallo screening e successivamente fino a 4 mesi (femmine) o 7 mesi (maschi) dopo il termine del trattamento con RBV. Nota: dal momento che i contraccettivi ormonali potrebbero non essere efficaci durante il trattamento con telaprevir, i soggetti per essere eleggibili al programma ad accesso precoce, devono utilizzare altri 2 metodi contraccettivi efficaci non ormonali durante il trattamento combinato con telaprevir e nei 2 mesi successivi all’ultima dose di telaprevir. Firma consenso informato ad attestare che il soggetto comprende gli scopi e procedure dell’EAP e desiderano prenderne parte. Firma del consenso informato per la ricerca farmacogenomica opzionale su DNA. Il rifiuto di firmare tale documento non preclude la partecipazione del sogg allo studio.

E.4

Principal exclusion criteria

Eligible for enrollment into an ongoing clinical study of telaprevir. Infected or coinfected with HCV of another genotype than genotype 1.Contraindication to the administration of Peg-IFN-alfa or RBV, or medical history or laboratory values that preclude treatment with Peg-IFN-alfa or RBV according to RCP.Contraindication to the currently prescribed HAART regimen at screening. Note: Subjects with contraindication to a nonprescribed permissible HAART medication are not excluded.Positive HLA-B5701 genotyping result at screening if abacavir is a component of HAART.Planned treatment holiday for HAART regimen.History of having received investigational HCV protease or polymerase inhibitors.Signs or symptoms of HCC.Serum alpha-fetoprotein (AFP) level and ultrasonography should be available at screening.History of decompensated liver disease.Coinfection with active hepatitis B.Inadequately controlled thyroid function.Baseline increased risk for anemia.Congenital QT prolongation or family history of congenital QT prolongation or sudden death. History of severe psychiatric disease. History of immunologically mediated disease. Any systemic antineoplastic or immunomodulatory (eg, systemic corticosteroids) treatment or radiation within 24 weeks before Day 1 or the expectation that such treatment will be needed at any time during the early access program.Presence of acute or active conditions of HIV (clinical grades 3 or 4 within 6 months before start of treatment.Stage C opportunistic infection occurring within the 6 months before start of treatment.Clinical evidence of chronic pulmonary disease associated with functional impairment.History of uncontrolled severe seizure disorders.History or other evidence of a clinically relevant ophthalmologic disorder due to diabetes mellitus or hypertension or history or other evidence of severe retinopathy.History of major organ transplantation with an existing functional graft with the exception of corneal transplants and skin grafts.Currently enrolled in an investigational drug study or has participated in such a study within 30 days before Day 1.Woman who is pregnant or breast-feeding. Any condition (including, but not limited to, alcohol and drug use), which, in the opinion of the investigator, could compromise the subject’s safety or adherence to the early access program.

Idoneità all'arruolamento in uno studio con telaprevir in corso. Infezione o co-infezione da HCV di genotipo diverso da 1. Controindicazione alla somministrazione di PEG-IFN-alfa o RBV, o storia di malattia o valori di laboratorio che precludano il trattamento con PEG-IFN–alfa o RBV secondo RCP in vigore. Controindicazione al trattamento HAART prescritto. Nota: i sogg con controindicazione a un regime HAART permesso non prescritto non sono esclusi. Genotipo positivo per HLA-B5701 allo screening se abacavir è parte del regime HAART. Sogg. che abbia già pianificato periodo di sospensione trattamento HAART. Storia di assunzione di inibitori della proteasi o polimerasi dell’HCV di tipo sperimentale. Segni o sintomi di carcinoma epatocellulare. Livello di alfa-fetoproteina nel siero ed ecografia dovrebbero essere disponibili allo screening. Storia e altre evidenze di malattia epatica scompensata. Co-infezione da virus dell’epatite B. Controllo non adeguato della funzionalità tiroidea. Aumentato rischio al basale di anemia. Prolungamento congenito del tratto QT o storia famigliare di prolungamento congenito del tratto QT o morte improvvisa. Storia di malattia psichiatrica. Storia di malattia immunologica mediata. Ha ricevuto qualunque trattamento sistemico antineoplastico o immunomodulatorio o ha ricevuto una radiazione entro 24 sett precedenti il giorno 1 o si prevede che questo trattamento sia necessario in qualunque momento durante l’EAP. Presenza di condizioni acute o attive di infezione da HIV (grado clinico 3 o 4) entro i precedenti 6 mesi prima dell’inizio del trattamento. Storia di infezione opportunistica di grado C del CDC entro i precedenti 6 mesi prima dell’inizio del trattamento. Evidenza clinica di malattia cronica polmonare associata a un danno funzionale. Storia di convulsioni non controllate. Storia o altre evidenze di importanti disordini clinici oftalmologici dovuti a diabete mellito oppure ipertensione o storia o altre evidenze di retinopatie gravi. Storia di trapianto di organo con un precedente graft funzionale ad eccezione di trapianti di cornea e grafts cutanei. Attualmente arruolato in uno studio sperimentale o ha partecipato in uno studio sperimentale nei 30 gg prima del Giorno 1.Donna incinta o che sta allattando al seno. Ha una condizione clinica che, secondo giudizio del medico sperimentatore, comprometterebbe la salute del paziente o l’accesso all’EAP o impedirebbe al soggetto di rispettare ed effettuare tutte le procedure dell’EAP.

E.5 End points

E.5.1

Primary end point(s)

Treatment-emergent adverse events

Valutazione degli eventi avversi derivanti da trattamento

E.5.1.1

Timepoint(s) of evaluation of this end point

from first use of the medicinal product to 30 days after administration of the last dose of investigational product (telaprevir)

Dal primo uso del prodotto medicinale fino a trenta giorni dopo la somministrazione dell'ultima dose di telaprevir.

E.5.2

Secondary end point(s)

NAP

E.5.2.1

Timepoint(s) of evaluation of this end point

NAP

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

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

Yes

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

Tolerability

Tollerabilità

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

E.8.1.1

Randomised

E.8.1.2

Open

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)

Information not present in EudraCT

E.8.2.2

Placebo

Information not present in EudraCT

E.8.2.3

Other

Information not present in EudraCT

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

Yes

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

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

Russian Federation

Switzerland

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

With the last evaluation performed on the last participating subject. Therefore the last evaluation before TVR becomes commercially available in Italy

Lo studio viene considerato completato con l'ultima valutazione dell'ultimo soggetto partecipante. Cioe' l'ultima valutazione prima che venga concessa l'autorizzazione all'immissione in commercio in Italia di Telaprevir.

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

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:

980

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.4.2

For a multinational trial

F.4.2.1

In the EEA

900

F.4.2.2

In the whole clinical trial

1000

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)

care of the patient according to the routine clinical practice

cura del paziente secondo la 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

2012-02-14

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-01-12

P. End of Trial
P.	End of Trial Status	Completed

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