A Study to Evaluate Safety and Efficacy of Subcutaneous Administration of Anakinra in Patients with CF

Inclusion Criteria:

1. Age ≥ 18 years (1st cohort). If justified by interim analysis, 18 > age ≥ 12 years (2nd cohort),

2. Informed consent of the patient (if applicable) and/or all legal guardians,

3. Sufficient fluency of patient and/or his/her representative in German language tocomply with study-specific procedures (e.g. to complete required quality of lifequestionnaires),

4. Confirmed diagnosis of cystic fibrosis, fulfilling at least one of the followingthree criteria:

5. sweat chloride ≥ 60mEq/L,

6. two CF causing mutations in the CFTR gene,

7. alterations of transepithelial potential difference of nasal or rectalepithelia typical for CF,

8. FEV1 ≥ 50 % pred. at screening,

9. LCI2.5 ≥ 7.05 at screening,

10. Ability to perform reproducible multiple breath washout and spirometry,

11. Oxyhaemoglobin saturation of ≥ 90% on room air at screening,

12. No changes in the medication for cystic fibrosis lung disease for at least 4 weeksprior to the first administration of the IMP of each treatment period (in case ofmedication changes in Period 1 and/or the washout phase the wash-out may be extendedfor up to 12 weeks in order to fulfill this criterion),

13. Adequate bone marrow function assessed on the basis of: neutrophils >1.5 x 109/L,platelets >100 x 109/L, hemoglobin >9.0 g/dL,

14. Adequate liver function assessed on the basis of: GGT, ASAT, and ALAT <3 x upperlimit of normal (ULN),

15. Adequate blood clotting assessed on the basis of: aPTT <39 sec., INR <1.2,

16. Negative serology for HIV (anti-HIV 1/2 IgG/IgM and p24-Ag), HBV (anti-HBsquantitative and anti-HBc IgG/IgM) and HCV (anti-HCV IgG), negative Interferon-gammarelease assay,

17. Negative Beta-HCG blood/urine test in women of childbearing potential (ofchildbearing potential are females who have experienced menarche and are notpermanently sterile or postmenopausal (postmenopausal: 12 consecutive months with nomenses without an alternative medical cause)),

18. Use of adequate contraception in sexually active female subjects (sexual abstinence,hormonal contraceptives or intrauterine device).

Exclusion Criteria:

1. Expected non-compliance, i.e. inability or unwillingness to comply withstudy-specific procedures,

2. Known allergy to anakinra or any ingredient of the pharmaceutical formulation ofKineret®,

3. Planned immunization with attenuated (live) vaccine(s) during the treatment with theIMP or completed immunization with attenuated (live) vaccine(s) within 4 weeks priorto the first administration of the IMP,

4. Renal failure (creatinine in serum above ULN),

5. History of tuberculosis or repeated detection of non-tuberculous mycobacteria fromairway samples in the last 12 months before start of each treatment period,

6. History of detection of Burkholderia cenocepacia species in the last 12 monthsbefore start of each treatment period,

7. Colonization with multi-resistant Staphylococcus aureus (MRSA) and/or 4-multi-resistant gram negative (MRGN) Pseudomonas aeruginosa is only an exclusioncriterion if the treating physician judges that this is an increased risk for thepatient,

8. Acute bronchopulmonary exacerbation (defined by modified Fuchs criteria (1) (seeAppendix 1), modification includes all ways of application of an antibiotic (e.g.,oral, i.v., inhaled)) within 14 days prior to the screening and before start of eachtreatment period,

9. Signs of other active infection within 14 days prior to the screening and beforestart of each treatment period (clinical symptoms (e.g. burning sensation whileurinating, skin, wound or dental infection) and/or fever and/or deterioration ofinfection-specific laboratory parameters beyond changes driven by the underlyingdisease),

10. Immunosuppressive treatment due to organ transplantation, rheumatic or autoimmunediseases as well as treatment with Anakinra in the last 3 months before Day 1 ofPeriod 1,

11. Participation in another interventional trial within the last 30 days prior toscreening,

12. Current oral corticosteroid use,

13. Current oxygen supplementation,

14. Current treatment with etanercept,

15. Medical history of lung transplantation,

16. Pregnant or nursing females (females of childbearing potential must have a negativepregnancy test at Screening),

17. Known hypersensitivity to hypertonic saline (used for induction of sputum).