Clinical Trials Register

Summary
EudraCT Number:	2007-001789-34
Sponsor's Protocol Code Number:	OptiB2007
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:	2008-01-04
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

2007-001789-34

A.3

Full title of the trial

A multicenter open label study to explore the efficacy and tolerability of Tenofovir DF (TDF) (300 mg) in chronic hepatitis B, HBeAg positive or negative, patients with suboptimal response to adefovir (ADV) or ADV/LAM treatment, defined as HBV-DNA levels > 10.000 copies/ml after an ADV or ADV+LAM treatment of > 48 weeks

Studio multi-centrico in aperto per valutare l'efficacia e tollerabilita` di tenofovir DF (TDF) (300 mg) in pazienti con epatite B cronica, HBeAg positiva o negativa, con risposta sub-ottimale ad un trattamento con adefovir (ADV) o ADV/LAM (lamivudina), definita come persistenza di valori di HBV-DNA > 10.000 copie/ml durante un trattamento con ADV o ADV+LAM per > 48 settimane

A.3.2

Name or abbreviated title of the trial where available

OptiB: Optimizing treatment for Chronic Hepatitis B patients

OptiB: Optimizing treatment for Chronic Hepatitis

A.4.1

Sponsor's protocol code number

OptiB2007

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 UNIVERSITARIA POLICLINICO UMBERTO I DI ROMA
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
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation
B.5.2	Functional name of contact point

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.2.1.2	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	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	TENOFOVIR DSOPROXIL FUMARATE
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.3	Concentration number	245
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	Non Applicabile

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 B HBV

Epatite B cronica HBV

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	10019731
E.1.2	Term	Hepatitis B
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

• Val la capacita' di un trattamento prolungato con TDF (300 mg/die) +/- LAM (100 mg/die) di indurre la soppressione ottimale della replicazione di HBV (livelli HBV-DNA < 400 copie/ml) e controllo della malattia epatica (livelli ALT normali) nell'epatite cronica B HBeAg positiva e anti-HBe positiva con risposta sub-ottimale alla terapia ADV o ADV/LAM.
• Valutare la durabilita' della soppressione completa della replicazione HBV (livelli HBV-DNA < 400 copie/ml) e del controllo della malattia epatica (livelli ALT normali) indotti da TDF (300 mg/giorno) +/- LAM (100 mg/giorno) nell'epatite cronica B HBeAg positiva e anti-HBe positiva con risposta sub-ottimale alla terapia ADV o ADV/LAM.
• Valutare la capacita' di un trattamento prolungato con TDF (300 mg/giorno) +/- LAM (100 mg/giorno) di indurre perdita dell'HBeAg, siero-conversione anti-HBe e controllo della malattia epatica (livelli ALT normali) nell'epatite cronica B HBeAg positiva con risposta sub-ottimale alla terapia ADV o AD

• Valutare l'efficacia della terapia TDF (300 mg/giorno) +/- LAM (100 mg/giorno) per indurre una soppressione ottimale della replicazione di HBV (livelli HBV-DNA < 400 copie/ml) ed un controllo della malattia epatica (livelli ALT normali) nell'epatite cronica B HBeAg positiva e anti-HBe positiva con risposta sub-ottimale alla terapia con ADV o ADV/LAM

E.2.2

Secondary objectives of the trial

• To evaluate the capability of a prolonged treatment with TFD (300 mg/die) +/- LAM (100 mg/die) to induce optimal suppression of HBV replication (HBV-DNA levels < 400 copies/ml) and control of liver disease (normal ALT levels) in HBeAg +ve and anti-HBe +ve CHB with suboptimal response to ADV or ADV/LAM therapy
• To evaluate the durabity of the optimal suppression of HBV replication (HBV-DNA levels < 400 copies/ml) and control of liver disease (normal ALT levels) induced by TDF (300 mg/die) +/- LAM (100 mg/die) in HBeAg +ve and anti-HBe +ve CHB with suboptimal response to ADV or ADV/LAM therapy
• To evaluate the capability of a prolonged treatment with TFD (300 mg/die) +/- LAM (100 mg/die) to induce HBeAg loss and seroconversion.and control of liver disease (normal ALT levels) in HBeAg +ve CHB with suboptimal response to ADV or ADV/LAM therapy
• To evaluate the durabity of HBeAg loss and seroconversion.and control of liver disease (normal ALT levels) in HBeAg +ve CHB with

• cap di un tratt prolungato con TDF(300 mg/die)+/- LAM(100 mg/die) (TRATT) di indurre la soppressione ottimale della replicazione di HBV(livelli HBV-DNA<400 copie/ml)e controllo della malattia epatica nell HBeAg+ e anti-HBe+ con risp sub-ottimale alla terapia ADV o ADV/LAM•durabilita' della soppressione completa della replicazione HBV(livelli HBV-DNA<400 copie/ml)e del controllo della malattia epatica indotti da TRATT nell'HBeAg+ e anti-HBe+ con risp sub-ottimale alla terapia ADV o ADV/LAM•cap di un tratt prolungato con TRATT di indurre perdita dell'HBeAg,siero-conversione anti-HBe e controllo della malattia epaticanellHBeAg+ con risp sub-ottimale alla terapia ADV o ADV/LAM•durabilita' della scomparsa dell'HBeAg,della siero-conversione anti-HBe e del controllo della malattia epatica nell'HBeAg positiva con risp sub-ottimale alla terapia ADV o ADV/LAM•sicur.e toll della terapia TDF+/- LAM in paz con HBeAg+ anti-HBe+ con risp sub-ottimale alla terapia ADV o ADV/LAM

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• > 18 years of age
• Chronic HBV infection, defined as positive serum HBsAg for at least 6 months
• Active chronic HBV infection with all the following:
 Currently treated with adefovir dipivoxil 10 mg QD or the combination of adefovir dipivoxil 10 mg QD and lamivudine 100 mg QD (for  48 weeks)
 HBeAg+ve or anti-HBe+ve at screening
 Serum HBV DNA  104 copies/mL
 Serum ALT  20  ULN
 Hemoglobin  8 g/dL
 Neutrophils  750 /mm3
• Adefovir or lamivudine-experienced
• Negative serum -HCG
• Compliant with adefovir dipivoxil
• Willing and able to provide written informed consent

 Soggetti adulti (>18 anni),
 epatite cronica B (definita come HBsAg positivo per almeno sei mesi),
 infezione attiva da epatite cronica B con tutti i seguenti criteri:
- trattati correntemente con adefovir dipivoxil 10 mg /giorno (per  48 settimane), da solo o in combinazione con lamivudina (100 mg/giorno)
- HBeAg positivo o anti-HBe positivo allo screening
- HBV-DNA nel siero >104 copie/mL alla visita di selezione
- ALT 20 il limite superiore di normalita' (UDM)
- Emoglobina ≥ 8 g/dL
- Neutrofili ≥ 750 mm3
 ß-HCG negativo nel siero
 in grado di dare consenso informato

E.4

Principal exclusion criteria

• Pregnant women, women who are breastfeeding or who believe they may wish to become pregnant during the course of the study.
• Male or females of reproductive potential who are unwilling to put into action all necessary steps to avoid pregnancy while enrolled in the study.
• Prior use of tenofovir DF or entecavir
• Received treatment with interferon or pegylated interferon within 6 months of the screening visit.
• Co-infection with HCV (based on serology), HIV, or HDV.
• Significant renal, cardiovascular, pulmonary, or neurological disease.
• Received solid organ or bone marrow transplantation.
• Currently receiving therapy with immunomodulators (e.g., corticosteroids, etc.), investigational agents, nephrotoxic agents, agents capable of modifying renal excretion.
• Proximal tubulopathy
• Known hypersensitivity to the study drugs (tenofovir DF or emtricitabine/tenofovir DF), the metabolites (tenofovir or emtricitabine) or formulation excipients.

 Donne in stato di gravidanza, allattamento o che intendano concepire durante il trattamento.
 Uomini o Donne in eta' fertile che non accettino di prendere tutte le misure necessarie per evitare una gravidanza durante il corso della terapia.
 Uso precedente di Tenofovir DF o di Entecavir
 Pazienti che hanno ricevuto interferone o interferone pegilato entro 6 mesi dalla data di screening
 Co-infezioni con HCV (sierologia) HIV o HDV
 Rilevanti patologie renali, polmonari o neurologiche
 Trapiantati d'organo o midollo
 In terapia corrente con immunomodulatori (corticosteroidi etc), agenti sperimentali, agenti nefrotossici, agenti in grado di modificare l'escrezione renale
 Tubolopatie prossimali
 Ipersensibilita' nota al farmaco sperimentale (tenofovir o emtricitabina) o agli eccipienti della formulazione

E.5 End points

E.5.1

Primary end point(s)

• Valutare la capacita' di un trattamento prolungato con TDF (300 mg/die) +/- LAM (100 mg/die) di indurre la soppressione ottimale della replicazione di HBV (livelli HBV-DNA < 400 copie/ml) e controllo della malattia epatica (livelli ALT normali) nell'epatite cronica B HBeAg positiva e anti-HBe positiva con risposta sub-ottimale alla terapia ADV o ADV/LAM.
• Valutare la durabilita' della soppressione completa della replicazione HBV (livelli HBV-DNA < 400 copie/ml) e del controllo della malattia epatica (livelli ALT normali) indotti da TDF (300 mg/giorno) +/- LAM (100 mg/giorno) nell'epatite cronica B HBeAg positiva e anti-HBe positiva con risposta sub-ottimale alla terapia ADV o ADV/LAM.
• Valutare la capacita' di un trattamento prolungato con TDF (300 mg/giorno) +/- LAM (100 mg/giorno) di indurre perdita dell'HBeAg, siero-conversione anti-HBe e controllo della malattia epatica (livelli ALT normali) nell'epatite cronica B HBeAg positiva con risposta sub-ottimale alla terapia ADV o ADV or ADV/LAM

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

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.8.2.3.1

Comparator description

terapia di salvataggio in caso di risposta sub-ott

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

Information not present in EudraCT

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

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	No
F.1.1	Number of subjects for this age range:	0
F.1.1.1	In Utero	No
F.1.1.2	Preterm newborn infants (up to gestational age < 37 weeks)	No
F.1.1.3	Newborns (0-27 days)	No
F.1.1.4	Infants and toddlers (28 days-23 months)	No
F.1.1.5	Children (2-11years)	No
F.1.1.6	Adolescents (12-17 years)	No
F.1.2	Adults (18-64 years)	Yes
F.1.3	Elderly (>=65 years)	Yes
F.2 Gender
F.2.1	Female	Yes
F.2.2	Male	Yes
F.3 Group of trial subjects
F.3.1	Healthy volunteers	No
F.3.2	Patients	Yes
F.3.3	Specific vulnerable populations	Yes
F.3.3.1	Women of childbearing potential not using contraception	Yes
F.3.3.2	Women of child-bearing potential using contraception	No
F.3.3.3	Pregnant women	No
F.3.3.4	Nursing women	No
F.3.3.5	Emergency situation	No
F.3.3.6	Subjects incapable of giving consent personally	No
F.3.3.7	Others	No
F.4 Planned number of subjects to be included
F.4.1	In the member state	150

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

2007-10-05

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2007-04-26

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

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