Efficacy Study of IgY (Antibody Against Pseudomonas) in Cystic Fibrosis Patients (PsAer-IgY)

Phase III Study 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

The purpose of this study is to prolong the time to reinfection with Pseudomonas aeruginosa after successfully treated acute or intermittent infection.

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Drug: IgY; Drug: Placebo

Detailed Description

This is a double -blind, placebo controlled study in which the investigational drug and the reference placebo group are gargled and swallowed. 70 ml IgY/ placebo solution is gargled every night for two minutes (for maximal 24 months) The design will include the recruitment of 144 patients randomized in two groups (72 per treatment group) In order to compensate for dropouts (i.e. patients dropping out prior to 24 months without having an event) the total sample size was planned to be approximately 180 (i.e. ~20 % dropout rate). After the actual drop-out rate has been low throughout the study, only 144 plus approx. 10% potential drop-outs were included into the study.

During the two years of treatment, subjects will be examined at the clinic every 3 months regarding safety and efficacy of the medication.

For more information please see www.impactt.eu The IMPACTT Project is funded by EU within the Framework 7 Program. PsAer-IgY Studies is part of IMPACTT Project (Workpackage 2).

• Study Type: Interventional
• Enrollment (Actual): 164
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Innsbruck, Austria, 6020
    • Medizinische Universität Innsbruck Department für Kinderheilkunde, Päd III CF Zentrum
  • Salzburg, Austria, 5020
    • (SALK) Universitätsklink für Kinder- und Jugendheilkunde, Ambulanz für Allergien und Lungenerkrankungen
• Belgium
  • Brussels, Belgium, 1090
    • Clinic of Pediatric Respiratory Diseases, Infectious Diseases and Travel Clinic
  • Brussels, Belgium
    • Hôpital Universitaire Erasme, Service de Pneumologie
  • Leuven, Belgium, 3000
    • University Hospital Leuven, Kindergeneeskunde
• Germany
  • Berlin, Germany, 13353
    • Charité, Christiane Herzog Zentrum
  • Bochum, Germany, 44791
    • Klinikum der Ruhr Universität Bochum
  • Dresden, Germany, 01307
    • University Dresden
  • Düsseldorf, Germany, 40225
    • Universitätsklinikum Düsseldorf
  • Essen, Germany, 45122
    • Universitätsklinikum Essen
  • Frankfurt, Germany
    • Klinikum der Johann-Wolfgang- Goethe Universität Frankfurt
  • Freiburg, Germany, 79106
    • Universitätsklinikum Freiburg, Zentrum für Kinder- und Jugendmedizin
  • Gießen, Germany, 35392
    • Universitätsklinikum Giessen und Marburg GmbH
  • Hannover, Germany, 30625
    • MH Hannover (adults)
  • Hannover, Germany, 30625
    • MH Hannover (children)
  • Jena, Germany, 07740
    • Universitätsklinik Jena, Mukoviszidosezentrum
  • Kiel, Germany, 24116
    • Städtisches Krankenhaus Kiel GmbH
  • Köln, Germany, 50924
    • Universitätsklinik Köln
  • Mainz, Germany, 55131
    • Universitätsklinikum Mainz
  • Tübingen, Germany, 72076
    • Universitatsklinik Tubingen
  • Würzburg, Germany, 97080
    • Universitäts-Kinderklinik Würzburg
• Hungary
  • Budapest, Hungary, 1089
    • Heim Pal Hospital for Children
  • Budapest, Hungary, 1121
    • Országos Korányi TBC és Pulm. Intézet, XIX. J fsz. Kronikus-CF care
• Ireland
  • Cork, Ireland
    • Cork University Hospital
  • Dublin, Ireland, 12
    • Our Lady´s Children´s Hospital
  • Dublin, Ireland, 24
    • Tallagh Hospital
  • Limerick, Ireland
    • Mid-Western Regional Hospital
• Italy
  • Firenze, Italy, 50139
    • Centro Regionale Toscano di Riferimento per la Fibrosi Cistica
  • Genova, Italy, 16100
    • Istituto Ospedale Giannina Gaslini
  • Roma, Italy, 00161
    • Centro Regionale Fibrosi Cisica Lazio
  • Verona, Italy, 37126
    • Azienda Ospedaliera Universitaria Integrata di Verona
• Poland
  • Gdansk, Poland, 80-308
    • Szpital Dzieciecy Polanki im. Macieja Plazynskiego w Gdansku sp Z o.o. Poradnia Leczenia
  • Karpacz, Poland, 58-540
    • Centrum Medyczne Karpacz Spólka Akcyjna
  • Rabka - Zdrój, Poland, 34-700
    • NZOZ Sanatorium Cassia Villa Medica
  • Warsaw, Poland, 01-211
    • Instytut Matki i Dziecka Zaklad Mukowiscydozy
  • Łódź, Poland, 90-329
    • Wojewódzki Szpital Specjalistyczny im. M.Kopernika Ośrodek Pediatryczny im. dr J.Korczaka
• Spain
  • Barakaldo (Vizcaya), Spain, 48903
    • Hospital Universitario Cruces Neumologia, Pediatric pulmonology
  • Barcelona, Spain, 08035
    • Passeig Vall d´Hebron 119
  • Madrid, Spain, 28046
    • Hospital Infantil la Paz Sección de Neumologia Pediátrica
  • Málaga, Spain, 29011
    • Hospital Materno-Infantil Servicio de Pediatria
• Sweden
  • Stockholm, Sweden, 141 86
    • Karolinska University Hospital, Huddinge - CF-Centre
  • Uppsala, Sweden, 75185
    • Uppsala University Childrens Hospital, Akademiska sjukhuset, CF center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 and above (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.
• 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).

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, .
• 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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: IgY, gargling solution; Avian polyclonal anti-pseudomonas antibodies (IgY), 70 ml gargling solution contains 50 mg IgY with an activity against PA, once daily	Drug: IgY; Avian polyclonal anti-pseudomonas antibodies (IgY); Other Names: PsAer-IgY
Placebo Comparator: Placebo, gargling solution; 70 ml gargling solution without antibodies, once daily	Drug: Placebo; Placebo, 70 ml gargling solution, once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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	max. 24 months

Secondary Outcome Measures

Outcome Measure	Time Frame
• Change in FEV 1.0 from day 0 to each visit	max. 24 months
• Change in BMI from day 0 to each visit	max. 24 months
• Number of exacerbations	max. 24 months
• Number of days of illness in hospital and at home, i.e. out of school or work	max. 24 months
• Control of use of antibiotics, especially anti-pseudomonas antibiotics -measured as days with antibiotic treatment	max. 24 months
• Change in values of serologic tests for PA precipitins from day 0 to each visit (if applicable)	max. 24 months
• Good tolerability and comparable number and quality of adverse events like placebo group	max. 24 months
• Sputum or throat cough swab or endolaryngeal suction cultures for bacteria and fungi	max. 24 months

Collaborators and Investigators

• Sponsor: Mukoviszidose Institut gGmbH
• Investigators: Principal Investigator: Antje Schuster, Prof. Dr., Universitätsklinikum Düsseldorf

Study record dates

Study Major Dates

• Study Start: October 1, 2011
• Primary Completion (Actual): June 27, 2017
• Study Completion (Actual): June 27, 2017

Study Registration Dates

• First Submitted: October 18, 2011
• First Submitted That Met QC Criteria: October 19, 2011
• First Posted (Estimate): October 20, 2011

Study Record Updates

• Last Update Posted (Actual): July 6, 2017
• Last Update Submitted That Met QC Criteria: July 3, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: cystic fibrosis
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Infections; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Pancreatic Diseases; Fibrosis; Cystic Fibrosis; Pseudomonas Infections
• Other Study ID Numbers: PsAer-IgY

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided