Clinical Trials Register

Summary
EudraCT Number:	2011-000801-39
Sponsor's Protocol Code Number:	PsAer-IgY
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:	2012-06-21
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

2011-000801-39

A.3

Full title of the trial

Prospective randomized, placebo-controlled, double blind, multicenter study (phase III) to evaluate clinical efficacy and safety of avian polyclonal anti-Pseudomonas antibodies (IgY) in prevention of recurrence of Pseudomonas aeruginosa infection in cystic fibrosis patients

Studio multicentrico, prospettico, controllato verso placebo, in doppio cieco, randomizzato (di fase III) per valutare l'efficacia e la sicurezza di anticorpi policlonali di origine aviaria anti-Pseudomonas (IgY) nella prevenzione delle infezioni ricorrenti da Pseudomonas aeruginosa in pazienti con Fibrosi Cistica

A.3.1

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

Placebo controlled clinical study to evaluate efficacy and safety of an antibody derived from hens'eggs building a barrier in the respiratory tract against Pesudomonas germ in order to preventi infection with Pseudomonas in patients suffering from cystic fibrosis

Studio clinico controllato verso il placebo per valutare l'efficacia e la tollerabilita' di un anticorpo derivato da tuorlo d'uovo, in grado di formare una barriera nel tratto respiratorio contro i germi Pseudomonas al fine di prevenire l'infezione da Pseudomonas in pazienti affetti da fibrosi cistica

A.3.2

Name or abbreviated title of the trial where available

IMPACTT -PsAer-IgY

A.4.1

Sponsor's protocol code number

PsAer-IgY

A.5.4

Other Identifiers

Name:

NCT01455675

Number:

clinicaltrials.gov

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	MUKOVISZIDOSE E.V.
B.1.3.4	Country	Germany
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	FP7 call for proposal Grant Agreement no. HEALTH-F2-2011-261095 Acronimo IMPACTT
B.4.2	Country	European Union
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Mukoviszidose Institute gGmbH
B.5.2	Functional name of contact point	Sponsor's project manager
B.5.3	Address:
B.5.3.1	Street Address	In den Dauen 6
B.5.3.2	Town/ city	Bonn
B.5.3.3	Post code	53117
B.5.3.4	Country	Germany
B.5.4	Telephone number	+49 228987800
B.5.5	Fax number	+49 2289878077
B.5.6	E-mail	impactt@muko.info

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	Yes
D.2.5.1	Orphan drug designation number	EU/3/08/564
D.3 Description of the IMP
D.3.1	Product name	avian polyclonal IgY antibody against PA
D.3.2	Product code	PsAer IgY
D.3.4	Pharmaceutical form	Oral solution
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oropharyngeal use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	IgY
D.3.9.2	Current sponsor code	PsAer - IgY
D.3.10	Strength
D.3.10.1	Concentration unit	ELISA unit/ml enzyme-linked immunosorbent assay unit/millitre
D.3.10.2	Concentration type	not less then
D.3.10.3	Concentration number	5
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)	Yes
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	Oral solution
D.8.4	Route of administration of the placebo	Oropharyngeal use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Cystic fibrosis (CF) is a chronic and progressive genetic disease of the body's exocrine glands. CF especially effects the respiratory system. A common effect leads to massive production of abnormal mucus of high viscosity, which clogs the airways and leads to infections. Pulmonary infections are major causes of morbility and mortality. PA infections are most common in CF patients and chronic infection with PA ultimately occurs in virtually all patients.

La Fibrosi Cistica (CF) è una malattia genetica cronica e progressiva delle ghiandole esocrine.CF colpisce particolarmente il sistema respiratorio. Un effetto è la produzione massiccia di una quantità anomala di muco ad alta viscosità che chiude le vie respiratorie e causa infezioni. La polmonite è la principale causa di morbilità e mortalità. L'infezione da PA è molto comune nei pazienti con CF e cronicizza in tutti i pazienti

E.1.1.1

Medical condition in easily understood language

For CF patients there is a high risk of chronical respiratory infections caused by PA bacteria. The prevention of infection with PA by the study medication is tested

Per i pazienti con CF il rischio di infezione respiratoria cronica causata da PA è molto elevata. Ci si propone di valutare l'efficacia del farmaco in studio nella prevenzione di tale infez

E.1.1.2

Therapeutic area

Diseases [C] - Bacterial Infections and Mycoses [C01]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	SOC
E.1.2	Classification code	10010331
E.1.2	Term	Congenital, familial and genetic disorders
E.1.2	System Organ Class	10010331 - Congenital, familial and genetic 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

The primary objective is to find out, if continuous long-term local application of specific egg yolk antibodies (IgY) directed against PA - initiated after successfully treated acute PA infection-can prolong the time to recurrence of sputum culture positive for PA. The objective to prevent infections with PA is also to diminish the need of antibiotics and minimize the problem of bacterial resistance against antibiotics.

L'obiettivo principale è provare se l'applicazione locale a lungo termine e continuativa di un anticorpo anti PA specifico del tuorlo d'uovo - iniziata dopo esito positivo del trattamento di un'infezione acuta da PA - può prolungare il tempo di reinfezione da PA, testata sullo sputo. Altro obiettivo è quello di diminuire gli interventi con antibiotici e di minimizzare il problema della resistenza batterica agli antibiotici.

E.2.2

Secondary objectives of the trial

• Change in FEV 1.0 from day 0 to each visit • Change in BMI from day 0 to each visit • Number of exacerbations • Number of days of illness in hospital and at home, i.e. out of school or work • Control of use of antibiotics, especially anti-pseudomonas antibiotics -measured as days with antibiotic treatment • Change in values of serologic tests for PA precipitins from day 0 to each visit (if applicable) Safety: • Good tolerability and comparable number and quality of adverse events like placebo group • Sputum or throat cough swab or endolaryngeal suction cultures for bacteria and fungi

Valutazione dei seguenti parametri:- FEV 1.0 all'inizio dello studio e a ciascuna visita; modifica di BMI all'inizio di ciascuna visita; numero delle reinfezioni; numero dei giorni di malattia in ospedale e a casa; uso di antibiotici anti PA; test serologici delle precipitine PA.In merito alla tollerabilità del farmaco: buona tollerabilità ed assenza di eventi avversi; culture di sputo o aspirato faringeo di funghi e batteri per valutare che non ci siano nuove infezioni batteriche (specialmente gram-negativi e micobatteri) o fungine (specialmente A.fumigatus) in assenza di PA.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• CF patients diagnosed according to specific clinical features and either a positive sweat chloride in double proofs or presence of disease-associated CFTR mutations in both alleles • Males and females > or = 5 years of age (being able to gargle) • CF patients having a FEV1 value between 50% and 130% of predicted value (according to Knudson formula) • CF patients who have had one to several sputum or throat cough swabs or endolaryngeal suction cultures positive for PA within the last three years and for whom PA has been successfully eradicated. • Sputum / throat cough swab/ endolaryngeal suction culture negative for PA and other gram-negative bacteria on study entry. • PA precipitins 0-1 on study entry • At inclusion no chronic infection with other gram-negative bacteria – such as B. cepacia, S. maltophilia and A. xylosoxidans – or atypical mycobacteria or Aspergillus fumigatus. • Patients and/ or their legal representative who are willing and able to give informed consent/ assent to participate in the study after thorough information • Subjects of child bearing potential and who are sexually active must meet the contraception requirements (i.e. oral or injectable contraceptives, intrauterine devices, double-barrier method, contraceptive patch, male partner sterilization or condoms).

Pazienti con CF diagnosticati secondo criteri clinici e positivi al test del cloro nel sudore eseguito in doppio alla presenza di mutazione del CFTR per entrambi gli alleli associate alla patologia - maschi e femmine di 5 o più anni in grado di fare gargarismi - pazienti CF con un valore di FEV 1 tra il 50% e il 130% predittivi secondo la formula Knudson - pazienti CF che hanno avuto uno o più culture positive per PA di sputo, espettorato o aspirato endolaringeo nell'arco degli ultimi tre anni e per i quali l'infezione da PA è stata eradicata con successo - cultura di sputo, espettorato o aspirato endolaringeo negativa per PA e altri gram negativi alla data di entrata nello studio - valori di precipitine PA fra 0 e 1 alla data di entrata nello studio - all'inclusione assenza di infezione croniche da altri gram negativi quali B. cepacia, S. maltophilia and A. xylosoxidans – o atipici micobatteri o Aspergillus fumigatus. - pazienti e/o loro legali rappresentanti che hanno siglato e sono in grado di dare consenso informato/ essere concordi a partecipare allo studio dopo dettagliata informazione - soggetti in età fertile e sessualmente attivi, in trattamento contraccettivo (contraccettivi orali o iniettabili, impianto intrauterino, metodo doppia barriera, cerotto contraccettivo, sterilizzazione del partner maschile, profilattico)

E.4

Principal exclusion criteria

• Microbiologic or serologic evidence of chronic infection with PA. Definition of chronic PA infection: Three cultures (sputum or throat cough swabs or endolaryngeal suction) have been positive for PA for 6 consecutive months (at least 3 cultures have to be taken) or more, or precipitins against PA are 2 or more in two tests taken at least 2 months apart. • Patients, who have positive sputum culture or throat cough swab or endolaryngeal suction culture for gram-negative bacteria, such as PA, S. maltophilia, B. cepacia, A. xylosoxidans (eradication before entry in study is possible), Patients, who have positive sputum culture or throat cough swab or endolaryngeal suction culture for atypical Mycobacteria and / or Aspergillus fumigates, associated with clinical symptoms that may necessitate specific treatment. • History of allergy/hypersensitivity to hens' egg proteins (including medication allergy) that is deemed relevant to the trial by the investigator. “Relevance” in this context refers to any increased risk of hypersensitivity reaction to trial medication. • Patient with a known relevant substance abuse, including alcohol or drug abuse. • Start of a new concomitant or chronic medication for CF within 4 weeks before inclusion. • Clinically relevant diseases or medical conditions other than CF or CF-related conditions that, in the opinion of the investigator, would compromise the safety of the patient or the quality of the data. This includes, but is not limited to, significant hematological, hepatic, renal, cardiovascular, and neurological diseases (diabetic patients may participate if their disease is under good control prior to inclusion). • Participation in another study with an investigational drug within one month or 6 half-lives (whichever is greater) preceding the inclusion. • The patient is an employee of the investigator or the institution with direct involvement in the trial or other trials under the direction of the investigator or their members. • Patients who are pregnant cannot be included into the study. This will be tested at inclusion visit with a urine pregnancy test (in female patients older than 10 years with secondary sexual characteristics)

- Evidenze microbiologiche o sierologiche di infezioni croniche da PA. Definizione di infezioni croniche da PA: tre culture (sputo, espettorato e aspirato endolaringeo) positive per PA per 6 mesi consecutivi (testato su almeno tre culture) o più; o valore di precipitine anti PA pari a 2 o più unità in due test eseguiti ad almeno due mesi di distanza. - Pazienti con cultura di sputo, espettorato o aspirato endolaringeo positivo per i batteri gram negativi quali PA, S. maltophilia, B. cepacia, A. xylosoxidans (eradicazione se possibile prima di entare nello studio), pazienti che hanno cultura di sputo, espettorato o aspirato endolaringeo positiva per Mycobacteria atipici e/o Aspergillus fumigates, associati a sintomi clinici che necessitano di un trattamento specifico. - storia di allergia/ipersinsibilità alle proteine del tuorlo d'uovo (incluso allergie ai farmaci) che si ritiene rilevante per lo studio da parte dello sperimentatore.''Rilevante'', in questo contesto, è definito in relazione ad ogni potenziale aumento di rischio di ipersensibilità per il farmaco in studio. - pazienti con noto abuso di farmaci quali alcol o droghe - pazienti che hanno iniziato un nuovo trattamento concomitante o un trattamento cronico per la fibrosi cistica nelle quattro settimane precedenti l'inclusione. - pazienti con patologie rilevanti o condizioni di salute correlate alla fibrosi cistica che a parere dello sperimentatore potrebbero compromettere la sicurezza del paziente o la qualità dei dati. Ciò include ma non è limitato a patologie importanti a carico del sangue, del fegato, del rene, del sistema cardiovascolare e neurologico (pazienti diabetici possono partecipare se la patologia è ben controllata farmacologicamente prima dell'inclusione) - paziente che ha partecipato ad un altro studio con un farmaco sperimentale nel mese precedente l'inclusione o nel periodo corrispondente a sei volte l'emivita del farmaco (considerando limitante il periodo più lungo fra i due citati) - paziente che lavori presso lo stesso ospedale o con lo sperimentatore, con un diretto coinvolgimento nello studio o in altri studi che fanno capo allo stesso sperimentatore o altri collaboratori - pazienti in gravidanza non possono essere inclusi nello studio. Un test specificio sarà effettuato prelevando urine alla visita di inclusione ( per tutte le pazienti di sesso femminile a partire dai 10 anni di età e sessualmente mature).

E.5 End points

E.5.1

Primary end point(s)

• Time from start of treatment (=Day 0) to the first recurrence of PA (Pseudomonas aeruginosa) in the sputum or throat cough swab or endolaryngeal suction.

Tempo intercorso dall'inizio del trattamento (giorno 0) alla prima infezione da PA nello sputo o nell'espettorato.

E.5.1.1

Timepoint(s) of evaluation of this end point

Eeach quartely visit and at unscheleduled additional visits because of exacerbation of adverse events or non-compliance

Ad ogni visita trimestrale e ad ogni ulteriore visita non prevista a seguito ricadute, eventi avversi o non-compliance

E.5.2

Secondary end point(s)

Valutazione dei seguenti parametri: - modifica della FEV 1.0 dal giorno 0 a ciascuna visita; modifica di BMI dal giorno 0 a ciascuna visita; numero delle reinfezioni; numero dei giorni di malattia in ospedale e a casa; uso di antibiotici anti PA; test serologici delle precipitine PA. In relazione alla tollerabilità del farmaco: buona tollerabilità ed assenza di eventi avversi; culture di sputo o aspirato faringeo di funghi e batteri per valutare che non ci siano nuove infezioni batteriche (specialmente gram-negativi e micobatteri) o fungine (specialmente A.fumigatus) in assenza di PA.

E.5.2.1

Timepoint(s) of evaluation of this end point

each quarterly visit

Ad ogni visita trimestrale

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

Yes

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

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

Yes

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

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

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 (week 104 +/- 7 days)or PA positive culture

LVLS (104° settimana +/- 7 giorni) o coltura positiva per PA

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

Number of subjects for this age range:

160

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:

100

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 of 5 years or more able to gargle.

popolazione pediatrica di età superiore ai 5 anni, in grado di fare gargarismi

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

180

F.4.2.2

In the whole clinical trial

180

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

2012-06-20

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-04-18

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2017-06-27

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