Clinical Trials Register

Summary
EudraCT Number:	2013-000133-12
Sponsor's Protocol Code Number:	SBR-ITA13
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2014-06-27
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

2013-000133-12

A.3

Full title of the trial

A randomized controlled multicentre open-label parallel arm study to assess the non-inferiority of the safety of bevacizumab compared to ranibizumab (allocation 4:1) administered by intravitreal injection in patients with macular degeneration or other exudative not age-related macular

Studio randomizzato controllato multicentrico in aperto a bracci paralleli per valutare la non-inferiorità della sicurezza di bevacizumab rispetto a ranibizumab (allocazione 4:1) somministrati per via intravitreale in pazienti con degenerazione maculare senile o altre maculopatie essudative non correlate all’età

A.3.1

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

A randomized controlled multicentre study to assess the non-inferiority of the safety of bevacizumab compared to ranibizumab administered by intravitreal injection in patients with macular degeneration or other exudative not age-related macular

Studio randomizzato controllato multicentrico per valutare la non-inferiorità della sicurezza di bevacizumab rispetto a ranibizumab somministrati per via intravitreale in pazienti con degenerazione maculare senile o altre maculopatie essudative non correlate all’età

A.3.2

Name or abbreviated title of the trial where available

SBR-ITA13

A.4.1

Sponsor's protocol code number

SBR-ITA13

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 Universitaria Integrata Verona
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	Azienda Ospedaliera Universitaria Integrata Verona
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	Azienda Ospedaliera Universitria Integrata Verona
B.5.2	Functional name of contact point	USRB
B.5.3	Address:
B.5.3.1	Street Address	P.le Stefani, 1
B.5.3.2	Town/ city	Verona
B.5.3.3	Post code	37126
B.5.3.4	Country	Italy
B.5.4	Telephone number	+390458127043
B.5.5	Fax number	+390458122814
B.5.6	E-mail	supporto.noprofit@ospedaleuniverona.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	AVASTIN
D.2.1.1.2	Name of the Marketing Authorisation holder	ROCHE 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	Concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravitreal use
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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	Yes
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	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	LUCENTIS
D.2.1.1.2	Name of the Marketing Authorisation holder	NOVARTIS FARMA 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	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravitreal use
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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	Yes
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

- Age-related macular degeneration
- Diabetic retinal oedema
- Retinal perivascular sheathing
- Choroidal neovascularisation

- degenerazione maculare senile essudativa
- edema maculare diabetico
- edema maculare da occlusione venosa centrale o di branca
- neovascolarizzazioni coroideali

E.1.1.1

Medical condition in easily understood language

- Age-related macular degeneration
- Diabetic retinal oedema
- Retinal perivascular sheathing
- Choroidal neovascularisation

- degenerazione maculare senile essudativa
- edema maculare diabetico
- edema maculare da occlusione venosa centrale o di branca
- neovascolarizzazioni coroideali

E.1.1.2

Therapeutic area

Diseases [C] - Eye Diseases [C11]

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

To evaluate the non inferiority of the safety of treatment with
bevacizumab vs ranibizumab, in particular about arteriothrombotic
events or death at 2 years

Valutare la non-inferiorità relativamente alla sicurezza del trattamento con bevacizumab vs ranibizumab in particolare per quanto riguarda gli eventi trombo-embolici o il decesso a 2 anni

E.2.2

Secondary objectives of the trial

1. To evaluate the efficacy of the treatment with bevacizumab vs
ranibizumab in terms of visual acuity at two years of the randomisation
2. To evaluate the proportion of the treatment with bevacizumab vs
ranibizumab serious adverse events at two years of the randomisation
3. To evaluate the proportion of the treatment with bevacizumab vs
ranibizumab gastrointestinal events at two years of the randomisation

1. Valutare l’efficacia del trattamento con bevacizumab vs ranibizumab in termini di acuità visiva a 2 anni dalla randomizzazione.
2. Valutare la proporzione di eventi avversi severi a 2 anni dalla randomizzazione del trattamento con bevacizumab vs ranibizumab.
3. Valutare la proporzione di eventi gastrointestinali a 2 anni dalla randomizzazione del trattamento con bevacizumab vs ranibizumab

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Age-related macular degeneration
or Diabetic retinal oedema
or Retinal perivascular sheathing
or Choroidal neovascularisation
patients
2. Men/woman
3. age ≥ 18 years

1. Pazienti affetti da degenerazione maculare senile essudativa, edema maculare diabetico, edema maculare da occlusione venosa centrale o di branca, neovascolarizzazioni coroideali
2. di entrambi i sessi
3. età ≥ 18 anni

E.4

Principal exclusion criteria

1. Patients treated with anti-VEGF intravitreal within the last six months
prior the inclusion in the study
2. Pregnancy or breast-feending
3. Patients in emergency situation
4. Subjects inable to give informed consent

1. pazienti precedentemente trattati con un anti-VEGF intravitreale nei 6 mesi precedenti all’arruolamento
2. Gravidanza o allattamento
3. pazienti in situazione di emergenza
4. soggetti incapaci di dare il proprio consenso informato

E.5 End points

E.5.1

Primary end point(s)

Proportion of subjects reporting deaths or non fatal-stroke or myocardial
infarction in the 2 years following randomization. Each subject is
counted once if experiencing multiple events.

Proporzione di soggetti che sono positivi ad almeno uno dei sottostanti eventi durante il periodo che va dal reclutamento a 2 anni dalla randomizzazione:
- Morte per tutte le cause
- Ictus non fatale
- Infarto al miocardio non fatale
Nel caso di positività a eventi multipli ogni soggetto viene conteggiato una volta

E.5.1.1

Timepoint(s) of evaluation of this end point

at 2 years

2 anni

E.5.2

Secondary end point(s)

- Differences between the two groups in the visual acuity score at 24
months from randomization. The visual acuity score is assessed using
differences in ETDRS letters from ETDRS charts.
- Proportion of participants reporting serious adverse events or worse in
the 2 years following randomisation. A serious adverse event is any
untoward medical
occurrence that at any dose:
1. Results in death
2. Is life-threatening at the time of the event
3. Requires in subject hospitalization or prolongation of existing
hospitalization
4. Results in persistent or significant disability/incapacity
5. Is a congenital anomaly or birth defect
- Proportion of participants reporting serious adverse gastrointestinal
events or worse in the 2 years following randomisation. Gastrointestinal
events considered are: abdominal hernia, abdominal pain, colitis
ulcerative, constipation, duodenal ulcer haemorrhage, gastric polyps,
gastric ulcer, gastric ulcer haemorrhage, gastritis, gastrointestinal
haemorrhage, gastrooesophageal reflux disease, ileus, lower
gastrointestinal haemorrhage, nausea, pancreatitis, rectal haemorrhage,
small intestinal obstruction, vomiting

- Differenza del punteggio di acuità visiva rilevata a 24 mesi dalla randomizzazione nei due gruppi. Il punteggio di acuità visiva viene rilevato tramite differenza delle lettere ETDRS tramite Tavole ETDRS-charts
- Proporzione di soggetti che hanno almeno un evento avverso di grado serio o superiore durante il periodo che va dal reclutamento a 2 anni dalla randomizzazione. Un evento avverso viene definito di grado serio se, a prescindere dalla dose, ha esito nella morte o mette in pericolo la vita del soggetto, richiede un ricovero ospedaliero o prolunga una degenza in ospedale, o che determina invalidità o incapacità gravi o prolungate, o comporta un’anomalia congenita o un difetto alla nascita.
- Proporzione di soggetti che hanno almeno un evento avverso serio o superiore di tipo gastrointestinale durante il periodo che va dal reclutamento a 2 anni dalla randomizzazione. Gli eventi avversi gastrointestinali considerati sono: ernia addominale, dolore addominale, colite ulcerosa, stipsi, ulcera duodenale emorragica, polipi gastrici, ulcera gastrica, gastrite, emorragia gastrointestinale, reflusso gastroesofageo, emorragia gastrointestinale ileale, nausea, pancreatite, emorragia rettale, ostruzione piccolo intestino, vomito.

E.5.2.1

Timepoint(s) of evaluation of this end point

from inclusion in the study to 2 years

dall'inclusione di un paziente nello studio a 2 anni

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

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)

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

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

ultima visita dell'ultimo soggetto arruolato

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.1.1.1

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:

280

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

1500

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

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

1780

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)

none

nessuno

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

2013-07-20

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-06-26

P. End of Trial
P.	End of Trial Status	Prematurely Ended

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