A Phase IIa, Randomized, Placebo-controlled, Double-blind, Cross-over Study to Evaluate Safety and Efficacy of Subcutaneous Administration of Anakinra in Patients With Cystic Fibrosis
OBJECTIVES Primary: To evaluate efficacy of treatment with anakinra in subjects with CF who are ≥ 12 years of age by means of lung clearance index (LCI). Secondary To evaluate safety and tolerability of treatment with anakinra as well as to investigate further effects of anakinra on lung function and quality of life (QOL) in subjects with CF.
• Age ≥ 18 years (1st cohort). If justified by interim analysis, 18 \> age ≥ 12 years (2nd cohort),
• Informed consent of the patient (if applicable) and/or all legal guardians,
• Sufficient fluency of patient and/or his/her representative in German language to comply with study-specific procedures (e.g. to complete required quality of life questionnaires),
• Confirmed diagnosis of cystic fibrosis, fulfilling at least one of the following three criteria:
∙ sweat chloride ≥ 60mEq/L,
‣ two CF causing mutations in the CFTR gene,
‣ alterations of transepithelial potential difference of nasal or rectal epithelia typical for CF,
• FEV1 ≥ 50 % pred. at screening,
• LCI2.5 ≥ 7.05 at screening,
• Ability to perform reproducible multiple breath washout and spirometry,
• Oxyhaemoglobin saturation of ≥ 90% on room air at screening,
• No changes in the medication for cystic fibrosis lung disease for at least 4 weeks prior to the first administration of the IMP of each treatment period (in case of medication changes in Period 1 and/or the washout phase the wash-out may be extended for up to 12 weeks in order to fulfill this criterion),
⁃ 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,
⁃ Adequate liver function assessed on the basis of: GGT, ASAT, and ALAT \<3 x upper limit of normal (ULN),
⁃ Adequate blood clotting assessed on the basis of: aPTT \<39 sec., INR \<1.2,
⁃ Negative serology for HIV (anti-HIV 1/2 IgG/IgM and p24-Ag), HBV (anti-HBs quantitative and anti-HBc IgG/IgM) and HCV (anti-HCV IgG), negative Interferon-gamma release assay,
⁃ Negative Beta-HCG blood/urine test in women of childbearing potential (of childbearing potential are females who have experienced menarche and are not permanently sterile or postmenopausal (postmenopausal: 12 consecutive months with no menses without an alternative medical cause)),
⁃ Use of adequate contraception in sexually active female subjects (sexual abstinence, hormonal contraceptives or intrauterine device).