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

• Register: EUCTR
• Last refreshed on: 6 November 2017
• Main ID: EUCTR2011-000801-39-DE
• Date of registration: 04/04/2011
• Prospective Registration: Yes
• Primary sponsor: Mukoviszidose Institute gGmbH
• Public title: 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
• Scientific title: 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 - IMPACTT-PsAer-IgY
• Date of first enrolment: 31/08/2011
• Target sample size: 180
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-000801-39
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Austria, Belgium, Germany, Hungary, Ireland, Italy, Spain, Sweden

Contacts

• Name: Sponsor´s Project Manager
• Affiliation: Mukoviszidose Institute gGmbH

• Name: Sponsor´s Project Manager
• Affiliation: Mukoviszidose Institute gGmbH

Key inclusion & exclusion criteria

Inclusion criteria:
1) 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.

2) Males and females ? 5 years of age (being able to gargle).

3) CF patients having a FEV1 value between 50% and 130% of predicted value (according to Knudson formula).

4) 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.

5) Sputum / throat cough swab/ endolaryngeal suction culture negative for PA and other gram-negative bacteria on study entry.

6)

7)

8) Patients and/ or their legal representative who are willing and able to give informed consent/ assent to participate in the study after thorough information.

9) 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).

Are the trial subjects under 18? yes
Number of subjects for this age range: 160
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 20
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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)



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

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.
MedDRA version: 17.1 Level: LLT Classification code 10011764 Term: Cystic fibrosis NOS System Organ Class: 100000004850

Therapeutic area: Diseases [C] - Bacterial Infections and Mycoses [C01]

Intervention(s)

Product Name: avian polyclonal IgY antibody against PA
Product Code: PsAer IgY
Pharmaceutical Form: Gargle
INN or Proposed INN: IgY
Current Sponsor code: PsAer IgY
Concentration unit: ELISA unit/ml enzyme-linked immunosorbent assay unit/millitre
Concentration type: not less then
Concentration number: 5-
Pharmaceutical form of the placebo: Gargle
Route of administration of the placebo: Oromucosal use

Primary Outcome(s)

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

Secondary Objective: - 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.

Main Objective: 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.

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

Secondary Outcome(s)

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.

Timepoint(s) of evaluation of this end point: each quarterly visit

Secondary ID(s)

PsAer-IgY

NCT01455675

Source(s) of Monetary Support

FP7 Call for Proposals Grant Agreemtent No.: HEALTH-F2-2011-261095 Acronym: IMPACTT