Clinical Trials Register

Summary
EudraCT Number:	2011-000801-39
Sponsor's Protocol Code Number:	PsAer-IgY
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2014-04-25
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Spain - AEMPS

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

Ensayo clínico multicéntrico (Fase III) prospectivo, aleatorizado, doble ciego, controlado con placebo, para evaluar la eficacia clínica y la seguridad de los anticuerpos policlonales anti-Pseudomonas de origen aviar (IgY) en la prevención de las recurrencias de infección por Pseudomonas aeruginosa en pacientes con fibrosis quística (ensayo PsAer-Igy)

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 the Pseudomonas germ in order to prevent infection with Pseudomonas in patients suffering from cystic fibrosis

Ensayo clínico controlado con placebo para evaluar la eficacia y seguridad de un anticuerpo procedente de los huevos de gallina para crear una barrera en el tracto respiratorio contra las bacterias Pseudomonas con el fin de prevenir la infección por Pseudomonas en pacientes con fibrosis quística

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:

clinicaltrials.gov

Number:

NCT01455675

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 Institute gGmbH
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 Proposals Grant Agreemtent No.: HEALTH-F2-2011-261095 Acronym: IMPACTT
B.4.2	Country	European Union
B.4.1	Name of organisation providing support	FP7-Infrastructures-2011-1.1.5: Facilities and resources for multinat. clinical trials: (ECRIN-IA)(284395)
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	+34946006451
B.5.5	Fax number	+34946006451
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 from September 23rd 2008
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	Gargle
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oromucosal 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	Gargle
D.8.4	Route of administration of the placebo	Oromucosal 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 affects 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 morbidity and mortality. Pseudomonas aeruginosa (PA) infections are most common in CF patients and chronic infection with PA ultimately occurs in virtually all patients.

La fibrosis quística (FQ) es una enfermedad genética crónica y progresiva de las glándulas exocrinas del cuerpo. CF afecta especialmente el sistema respiratorio. Un efecto común es la producción masiva de moco anormales de alta viscosidad, que obstruye las vías respiratorias y provocan infecciones, principales causas de morbilidad y mortalidad. la Pseudomonas aeruginosa (PA)es la infeccion más comun en todos los pacientes con FQ

E.1.1.1

Medical condition in easily understood language

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

Para los pacientes con FQ existe un alto riesgo de infecciones respiratorias crónicas causadas por bacterias Pseudomonas aeruginosa. Se prueba una medicación como prevención para la infección con PA.

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	16.1
E.1.2	Level	LLT
E.1.2	Classification code	10011764
E.1.2	Term	Cystic fibrosis NOS
E.1.2	System Organ Class	100000004850

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 a 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.

El objetivo principal es averiguar si una continua aplicacion local durante un largo periodo de anticuerpos de yema de huevo (IgY) específicos dirigidos contra PA - iniciada después de tratamiento con éxito de la infección aguda PA - puede prolongar el tiempo hasta la recurrencia de un cultivo positivo para PA.
El objetivo de prevenir las infecciones con PA es también para disminuir la necesidad de antibióticos y minimizar el problema de la resistencia bacteriana a los antibióticos.

E.2.2

Secondary objectives of the trial

- Change in FEV 1.0 from start to each visit
- Change in BMI from start 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 anti-pseudomonas antibiotics
- Serologic tests for PA precipitins
Safety
- Good tolerability and absence of adverse events
- Sputum or throat cough swab cultures for bacteria and fungi to ensure that there will not be any new bacteria (especially gram negative bacteria and mycobacteria) or fungi (especially A. fumigatus) appearing in the absence of PA.

Cambio en el FEV 1.0 del principio a cada visita
- Cambio en el IMC de principio a cada visita
- Número de exacerbaciones
- Número de días de enfermedad en el hospital y en casas, es decir, asusencia al colegio o trabajo
- Control del uso de antibióticos anti-pseudomonas
- Las pruebas serológicas para precipitinas PA
seguridad
- Buena tolerabilidad y ausencia de eventos adversos
- Cultivos de esputo o frotis de tos de garganta para bacterias y hongos para asegurar que no habrá ninguna nueva bacteria (especialmente bacterias gram negativas y micobacterias) u hongos (especialmente A. fumigatus) que aparecen en ausencia de 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 ? 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 on study entry. ? 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).

1. Pacientes con FQ diagnosticada de acuerdo a la existencia de caracteristicas clinicas especificas y bien un resultado positivo en dos ocasiones de una prueba de Cloro en sudor o la presencia de mutaciones CFTR asociadas a la enfermedad en ambos alelos.
2. Mujeres y hombres
3. Igual o mayores de 5 años (con capacidad para hacer gárgaras).
4. Pacientes con FQ que tengan un valor de FEV1 entre el 50% y el 130% del valor predicho (utilizando la fórmula de Knudson).
5. Pacientes con FQ que hayan tenido uno o varios esputos o frotis nasofaríngeos o aspirado nasal con cultivos positivos a PA en los últimos tres años y en los que el PA ha sido erradicado con éxito.
6. Esputo o frotis nasofaríngeo o aspirado nasal con cultivo negativo para PA al inicio del estudio.
7. Pacientes y/o sus representantes legales que están dispuestos y con capacidad para dar su consentimiento informado/ asentimiento para participar en el estudio después de recibir información completa.
8. Los individuos en edad fértil y que son sexualmente activos deberán de cumplir con los requisitos de anticoncepción (por ejemplo anticonceptivos orales o inyectables, dispositivos intrauterinos, métodos de doble barrera, parches anticonceptivos, esterilización de la pareja masculina o preservativos)

E.4

Principal exclusion criteria

1) 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.

2) 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) if treatment is to be expected which would be also effective against PA, 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.

3) 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.

4) Patient with a known relevant substance abuse, including alcohol or drug abuse.

5) Start of a new concomitant or chronic medication for CF within 4 weeks before inclusion.

6) 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).

7) Participation in another study with an investigational drug within one month or 6 half-lives (whichever is greater) preceding the inclusion.

8) 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.

9) 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)

1. Evidencia microbiológica o serológica de infección crónica de PA. Definición de infección crónica de PA: 3 cultivos (esputo o frotis nasofaríngeo o aspirado nasal) han sido positivos para PA durante 6 meses consecutivos (por lo menos se han obtenido 3 cultivos) o mas.
2. Pacientes que tienen un cultivo positivo de esputo o frotis nasofaríngeo o aspirado nasal para una bacteria gram-negativa, como PA, S. maltophilia, B. cepacia, , A. xylosoxidans (la erradicación antes de entrar al estudio es posible) si se espera que su tratamiento será también efectivo contra PA. Pacientes que tienen cultivo de esputo o frotis nasofaríngeo o aspirado nasal positivo para Micobacterias Atipicas y/o Aspergillus fumigates, asociados con síntomas clínicos que pueden requerir un tratamiento especifico.
3. Historial/antecedentes de alergia/hipersensibilidad a la proteína de huevo de gallina (incluyendo alergia a la medicación) que a criterio del investigador sea relevante para el estudio. ?Relevancia? en este contexto se refiere a todo aumento del riesgo de reacción de hipersensibilidad a la medicación del ensayo.
4. Paciente con abuso conocido y relevante de sustancias, incluyendo abuso de alcohol o de drogas.
5. Inicio de una nueva medicación concomitante o crónica para la FQ dentro de las 4 semanas anteriores a la inclusión.
6. Enfermedades o condiciones médicas clínicamente relevantes al margen de FQ o de condiciones relacionadas con la FQ que, a criterio del investigador, pudieran comprometer la seguridad del paciente o la calidad de los datos. Esto incluye, pero no se limita a, enfermedades hematológicas, hepáticas, renales, cardiovasculares y neurológicas (los pacientes diabéticos pueden participar si su enfermedad está bien controlada antes de la inclusión).
7. Participación en otro estudio con un fármaco en investigación dentro de un mes o 6 vidas medias (lo que sea mayor) antes de la inclusión.
8. Pacientes que sean empleados del investigador o del centro con implicación directa en el ensayo o en otros ensayos bajo la dirección del investigador o de otros miembros del equipo.
9. Pacientes que estén embarazadas. Esto será comprobado en la visita de inicio con un test de embarazo de orina (en pacientes mujeres mayores de 10 años con desarrollo de características sexuales secundarias)

E.5 End points

E.5.1

Primary end point(s)

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

? Tiempo desde el inicio del tratamiento (= Día 0) hasta la primera recurrencia de PA (Pseudomonas aeruginosa) en el esputo o frotis nasofaríngeo o aspirado endolaríngeo.

E.5.1.1

Timepoint(s) of evaluation of this end point

each quarterly visit and at unscheduled additional visits because of exacerbations or adverse events or non-compliance

cada visita trimestral y las visitas adicionales no programadas a causa de las exacerbaciones o eventos adversos o falta de cumplimiento

E.5.2

Secondary end point(s)

- Change in FEV 1.0 from start to each visit
- Change in BMI from start 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 anti-pseudomonas antibiotics
- Serologic tests for PA precipitins
Safety
- Good tolerability and absence of adverse events
- Sputum or throat cough swab or endolaryngeal suctioncultures for bacteria and fungi to
ensure that there will not be any new bacteria (especially gram
negative bacteria and mycobacteria) or fungi (especially A.
fumigatus) appearing in the absence of PA.

? Cambio en el FEV 1.0 desde el día 0 hasta cada visita.
? Cambio en el BMI (índice de masa corporal) desde el día 0 hasta cada visita.
? Número de exacerbaciones.
? Numero de días de enfermedad en el hospital y en casa (ausencias en el trabajo o en el colegio).
? Control del uso de antibióticos, especialmente antibióticos anti-pseudomonas- medidos como días con tratamiento antibiótico.
? Cambios en los valores de los test serológicos de precipitinas para PA desde la visita de selección hasta cada visita (si fuera aplicable).

E.5.2.1

Timepoint(s) of evaluation of this end point

each quarterly visit

cada visita trimestral

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

E.8.1.4

Double blind

Yes

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)

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

last visit last patient

la ultima visita del ultimo paciente

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:

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 aged >= 5 years

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)

normal treatment of CF patients

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

2014-07-25

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2014-06-10

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

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials