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. |
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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. |
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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 | LLT |
E.1.2 | Classification code | 10011764 |
E.1.2 | Term | Cystic fibrosis NOS |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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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. |
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E.2.2 | Secondary objectives of the trial |
Efficacy
• 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 (as
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 |
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E.2.3 | Trial contains a sub-study | No |
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 alleles1
• 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 swab or
endolaryngeal suction cultures positive for PA within the last three years and for
whom PA has been successfully eradicated
• Sputum (throat cough swab or endolaryngeal suction) culture neg. for PA and
other gram-neg bacteria on study entry.
• At inclusion no chronic infection/colonization with other gram-negative bacteria -
such as B. cepacia, S. maltofilia 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). |
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E.4 | Principal exclusion criteria |
• Microbiologic or serologic evidence of chronic infection with PA.
Definition of chronic PA infection: Three cultures (sputum or throat coughswabs 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 the 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). |
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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 or endolaryngeal suction. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
• 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 (as applicable)
• 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 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 28 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |