Clinical Trials Register

Summary
EudraCT Number:	2011-004351-39
Sponsor's Protocol Code Number:	FARM8MXYFL
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:	2012-03-13
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

2011-004351-39

A.3

Full title of the trial

Phase II, randomized, double arm, multi-center study evaluating the efficacy and safety of azithromycin for the long term prophylactic treatment of COPD in primary antibody deficiency patients with clinical and spirometrically confirmed COPD suffering from repeated acute exacerbations

STUDIO MULTICENTRICO RANDOMIZZATO IN DOPPIO CIECO DI FASE II PER LA VALUTAZIONE DELL'™EFFICACIA CLINICA E DELLA SICUREZZA DELL'AZITROMICINA NELLA PROFILASSI A LUNGO TERMINE DELLE RIACUTIZZAZIONI DELLA BPCO IN PAZIENTI AFFETTI DA DIFETTI PRIMITIVI DELL'™IMMUNITA' CON BPCO CONFERMATA CLINICAMENTE E CON SPIROMETRIA

A.3.1

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

STUDIO MULTICENTRICO RANDOMIZZATO IN DOPPIO CIECO DI FASE II PER LA VALUTAZIONE DELL’EFFICACIA CLINICA E DELLA SICUREZZA DELL’AZITROMICINA NELLA PROFILASSI A LUNGO TERMINE DELLE RIACUTIZZAZIONI DELLA BPCO IN PAZIENTI AFFETTI DA DIFETTI PRIMITIVI DELL’IMMUNITA' CON BPCO CONFERMATA CLINICAMENTE E CON SPIROMETRIA

A.4.1

Sponsor's protocol code number

FARM8MXYFL

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	AIFA (bandi per la ricerca indipendente)
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 Policlinico Umberto I
B.5.2	Functional name of contact point	UOD Reference Centre for Immunodefi
B.5.3	Address:
B.5.3.1	Street Address	Viale dell’Universita' 37
B.5.3.2	Town/ city	Roma
B.5.3.3	Post code	00185
B.5.3.4	Country	Italy
B.5.4	Telephone number	06-49972007
B.5.5	Fax number	06-49972007
B.5.6	E-mail	isabella.quinti@uniroma1.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	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	Azytromicyn
D.3.2	Product code	NA
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.3.9.2	Current sponsor code	FARM8MXYFL
D.3.9.3	Other descriptive name	Azithromycin
D.3.9.4	EV Substance Code	J01FA10
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	250
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Film-coated tablet
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

primary immunodefciency patients with COPD and frequent exacerbations

difetti primitivi dell'immunità umorale e da BPCO con frequenti riacutizzazioni ed associata asma grave

E.1.1.1

Medical condition in easily understood language

primary immunodefciency patients with COPD and frequent exacerbations

difetti primitivi dell'immunità umorale e da BPCO con frequenti riacutizzazioni ed associata asma grave

E.1.1.2

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

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	10029978
E.1.2	Term	Obstructive chronic bronchitis with acute exacerbation
E.1.2	System Organ Class	10021881 - Infections and infestations

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	10013289
E.1.2	Term	Disorders involving the immune mechanism
E.1.2	System Organ Class	10021428 - Immune system disorders

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	10003554
E.1.2	Term	Asthma aggravated
E.1.2	System Organ Class	10038738 - Respiratory, thoracic and mediastinal disorders

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

in the arm of patients under azythomycin prophylaxis we expect a superiority on the following end-point: - decrease annual episodes of acute COPD exacerbations defined as: - dyspnoea;- increased cough; -increased sputum volume and purulence

Nel braccio dei pazienti in antibioticoprofilassi con azitromicina in confronto con il braccio di pazienti trattati con placebo ci aspettiamo una superiorità nel seguente obiettivo: diminuzione delle riacutizzazioni di BPCO definite come: dispnea, aumento della tosse, aumento del volume e della purulenza dell’espettorato

E.2.2

Secondary objectives of the trial

in the arm of patients under azythomycin prophylaxis in respect to the arm of patients under placebo we expect a superiority on the following end-points: - decrease number of additional doses of antibiotics required for treatment of the exacerbations (other than the prophylactic antibiotics given as study medicine) - decrease in the number of patients not having an exacerbation during the course of the study - decrease in the recurrence time to next exacerbation - decrease of the duration of exacerbations (days of disability per exacerbation) - improvement of the Health Related Quality of Life measures - increase of FEV1 - reduction in the number of days of disability variously defined as days in bed, days off work or days where the subject is unable to undertake normal activities Safety analy sis: -calculate the number of adverse events

Nel braccio dei pazienti in antibioticoprofilassi con azitromicina ci aspettiamo una superiorità nei seguenti obiettivi: Diminuzione delle dosi addizionali di antibiotici necessari al trattamento delle riacutizzazioni (oltre al trattamento utilizzato per l’antibiotico-profilassi) Diminuzione nel numero di pazienti che non hanno riacutizzazioni durante la durata dello studio. Diminuzione nel tempo di ricorrenza della riacutizzazione successiva Diminuzione della durata delle riacutizzazioni (giorni di disabilità per riacutizzazione) Miglioramento degli indici di qualità di vita Aumento del FEV1 Riduzione nel numero di giorni di disabilità definito come giorni di allettamento, assenza lavorativa o da scuola, giorni nei qulai il paziente non può assolvere alle normali attività quotidiane Sicurezza: del numero di eventi avversi

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

•diagnosis of X-linked Agammaglobulinemia or Common Variable Immunodeficiency •male or female aged 12 to 74 years •clinical and spirometrically confirmed COPD •written informed consent.

• diagnosi di X-linked-Agammaglobulinemia o Immunodeficienza Comune Variabile • maschio o femmina di età compresa tra 12 e 74 anni • BPCO confermata clinicamente e con spirometria • consenso informato scritto

E.4

Principal exclusion criteria

• known allergic reaction to azithromycin • patients taking drugs that could adversely interact with macrolides • lymphoproliferative disease • Creatinine concentration >1.5 times the UNL • ASAT or ALAT concentration >2.5 times the UNL • HIV infection, acute hepatitis or clinically active chronic hepatitis • Pregnancy or breast feeding females planning to become pregnant during the course of the study • Any condition that is likely to interfere with the evaluation of the study drug or satisfactory conduct of the trial

• reazioni allergiche all’azitromicina • pazienti che effettuano trattamenti che interferiscono con l’azitromicina o altri macrolidi • malattie linfoproliferative • Creatininemia >1.5 volte il valore normale • ASAT or ALAT >2.5 times il valore normale • HIV infezione, epatite acuta o cronica • Gravidanza • Ogni altra condizione che possa interferire con la possibilità di valutare i risultati dello studio

E.5 End points

E.5.1

Primary end point(s)

Efficacy: Decrease annual episodes of acute COPD exacerbations defined as: - dyspnoea;- increased cough; -increased sputum volume and purulence. Safety: Adverse events (total, severe, fatal)

Endpoint di efficacia: Diminuzione degli episodi di esacerbazione della BPCO acuta definiti come: • dispnea • aumento della tosse • aumento di volume e della purulenza dello sputo Endpoint di sicurezza: Eventi avversi (totali, severi, fatali)

E.5.1.1

Timepoint(s) of evaluation of this end point

30 visits have been scheduled: 1 visit each month for the treatment period (24 months); 1 visit each month for the treatment period (6 months). During each visit will be performed the physical examination and will be collected informations concerning AE/SAE and the drug compliance. the patient will compile diaries and the SF36 questionnaire at visits 1, 12, 24 and 26. Sputum sample will be collected on each visit. Every 4 months will be performed the routine blood testing, urinalysis and FEV1 evaluation,

Sono state previste 30 visite complessive: una visita mensile di controllo per tutta la durata del trattamento (24 mesi); una visita al mese dopo il trattamento per un totale di 6 visite (6 mesi). Ad ogni visita verrà effettuato l’esame obiettivo e verranno raccolte le informazioni sugli eventi/reazioni avverse e sulla compliance al trattamento. Ai pazienti verrà fornito un diario per la registrazione dei cambiamenti e verrà chiesto di rispondere ai questionari sulla qualità della vita alle visite 1, 12, 24 e 26. Ad ogni visita verrà effettuatol’esame dello sputo. Ogni 4 mesi verranno effettuati esami ematochimici, delle urine ed una spirometria.

E.5.2

Secondary end point(s)

• Decrease number of additional doses of antibiotics required for treatment of the exacerbations (other than the prophylactic antibiotics given as study medicine) • Decrease in the number of patients not having an exacerbation during the course of the study -Decrease in the recurrence time to next exacerbation • Decrease of the duration of exacerbations (days of disability per exacerbation) • Improvement of the Health related quality of life measures • Increase of FEV1 • Reduction in the number of days of disability variously defined as days in bed, days off work or days where the subject is unable to undertake normal activities

• Riduzione del numero di dosi aggiuntive di antibiotico richieste per il trattamento delle esacerbazioni • Riduzione nel numero di pazienti senza esacerbazioni nel corso dello studio • Riduzione della durata delle esacerbazioni • Miglioramento dello stato di salute in relazione alla qualità di vita • Aumento della FEV1 • Riduzione dei giorni di disabilità definiti come giorni a letto, giornate di lavoro perse o giorni in cui il paziente era impossibilitato a svolgere le normali attività

E.5.2.1

Timepoint(s) of evaluation of this end point

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

Yes

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)

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

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

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)

E.8.2.2

Placebo

Yes

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

Yes

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

Yes

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)

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:

120

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 For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2012-03-13.

Yes

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

158

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)

Patients will continue to be treated at the Site.

Il paziente continuerà ad essere seguito presso il centro.

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

2011-10-28

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-10-27

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

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