ANAKINRA for Cystic fibrosis

Inclusion criteria

• {"criterion_text":"- Age ≥ 18 years (1st cohort). If justified by interim analysis, 18 > age ≥ 12 years (2nd cohort),\n- 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,\n- Adequate liver function assessed on the basis of: GGT, ASAT, and ALAT <3 x upper limit of normal (ULN),\n- Adequate blood clotting assessed on the basis of: aPTT <39 sec., INR <1.2,\n- Negative serology for HIV (anti-HIV 1/2 IgG/IgM and p24-Ag), HBV (people without history of HepB vaccination: anti-HBs quantitative and anti-HBc IgG/IgM must be negative; people with history of HepB vaccination: anti HBc IgG/IgM negative) and HCV (anti-HCV IgG), negative Interferon-gamma release assay (people with history of a latent infection with Mycobacterium tuberculosis (LTBI), documented adequate treatment of LTBI, and with airway samples negative for Mycobacterium tuberculosis can have a positive test result),\n- 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)),\n- Use of adequate contraception in sexually active female subjects (sexual abstinence, hormonal contraceptives or intrauterine device).\n- Informed consent of the patient (if applicable) and/or all legal guardians,\n- 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),\n- Confirmed diagnosis of cystic fibrosis, fulfilling at least one of the following three criteria: a. sweat chloride ≥ 60mEq/L, b. two CF causing mutations in the CFTR gene, c. alterations of transepithelial potential difference of nasal or rectal epithelia typical for CF,\n- FEV1 ≥ 50 % pred. at screening,\n- LCI2.5 ≥ 7.05 at screening,\n- Ability to perform reproducible multiple breath washout and spirometry,\n- Oxyhaemoglobin saturation of ≥ 90% on room air at screening,\n- 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),"}

Exclusion criteria

• {"criterion_text":"- Expected non-compliance, i.e. inability or unwillingness to comply with study-specific procedures,\n- Immunosuppressive treatment due to organ transplantation, rheumatic or autoimmune diseases as well as treatment with Anakinra in the last 3 months before Day 1 of Period 1,\n- Participation in another interventional trial within the last 30 days prior to screening,\n- Current oral corticosteroid use,\n- Current oxygen supplementation,\n- Current treatment with etanercept,\n- Medical history of lung transplantation,\n- Pregnant or nursing females (females of childbearing potential must have a negative pregnancy test at screening),\n- Known hypersensitivity to hypertonic saline (used for induction of sputum).\n- Known allergy to anakinra or any ingredient of the pharmaceutical formulation of Kineret®,\n- Planned immunization with attenuated (live) vaccine(s) during the treatment with the IMP or completed immunization with attenuated (live) vaccine(s) within 4 weeks prior to the first administration of the IMP,\n- GFR <60ml/min/1.73qm,\n- History of tuberculosis or repeated detection of non-tuberculous mycobacteria from airway samples in the last 12 months before start of each treatment period,\n- History of detection of Burkholderia cenocepacia species in the last 12 months before start of each treatment period,\n- Known colonization with multi-resistant Staphylococcus aureus (MRSA) and/or 4-multiresistant gram negative (MRGN) Pseudomonas aeruginosa is only an exclusion criterion if the treating physician judges that this is an increased risk for the patient,\n- Acute bronchopulmonary exacerbation (defined by modified Fuchs criteria (23) (see Appendix 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 each treatment period,\n- Signs of other active infection within 14 days prior to the screening and before start of each treatment period (clinical symptoms (e.g. burning sensation while urinating, skin, wound or dental infection) and/or fever and/or deterioration of infection-specific laboratory parameters beyond changes driven by the underlying disease),"}

Primary endpoints

• {"endpoint_text":"- Absolute pre-post change of the lung clearance index (LCI).","definition_or_measurement_approach":"Absolute change measured by lung clearance index (LCI) pre- and post-treatment (pre-post change of LCI)."}

Secondary endpoints

• {"endpoint_text":"- Evaluation of the safety and tolerability of the 28- days-treatment with anakinra by means of: o Physical examination o (Serious) adverse events o Laboratory safety parameters (clinical chemistry, hematology, clotting)","definition_or_measurement_approach":"Safety/tolerability assessed during 28-day treatment by physical examinations, recording (S)AEs, and laboratory safety parameters (clinical chemistry, hematology, clotting)."}
• {"endpoint_text":"- Investigation of the effects of anakinra on lung function by means of absolute change in percentage points predicted forced expiratory volume in 1 second (FEV1 and FEV1 % pred).","definition_or_measurement_approach":"Absolute change in FEV1 and FEV1 % predicted from baseline to post-treatment."}
• {"endpoint_text":"- Evaluation of the impact of anakinra on the quality-of-life (QoL) in the considered population by means of the Cystic Fibrosis Questionnaire – Revised (CFQ-R, German version).","definition_or_measurement_approach":"Quality of life assessed using CFQ-R (German version) with absolute/relative changes from baseline."}
• {"endpoint_text":"- Investigation of the effects of anakinra on lung function by means of absolute change in forced expiratory flow75 in liters/second and percent predicted (FEF75 and FEF75 % pred) and forced vital capacity in liter and percent predicted (FVC and FVC % pred).","definition_or_measurement_approach":"Absolute change in FEF75, FEF75 % pred, FVC and FVC % pred from baseline to post-treatment."}
• {"endpoint_text":"- Assessment of the influence of anakinra on lung structure and perfusion determined by chest MRI (optional sub-study).","definition_or_measurement_approach":"Optional chest MRI sub-study evaluating lung structure and perfusion changes pre- and post-treatment."}
• {"endpoint_text":"- Assessment of the influence of anakinra on airway inflammation by means of the following parameters: o Characterization of immune cells (absolute cell counts) in sputum samples o Inflammatory markers in sputum samples.","definition_or_measurement_approach":"Airway inflammation assessed by sputum immune cell counts and inflammatory marker measurements."}
• {"endpoint_text":"- Assessment of the influence of anakinra on the bronchial infection status by means of sputum microbiology.","definition_or_measurement_approach":"Bronchial infection status assessed by sputum microbiology (pathogen detection/quantitation)."}
• {"endpoint_text":"- Assessment of sputum rheology","definition_or_measurement_approach":"Sputum rheology measurements to assess physical properties of sputum pre- and post-treatment."}

Germany

Earliest CTIS Part Ii Submission Date

22-01-2024

Latest Decision Or Authorization Date

16-05-2024

Processing Time Days

115

Number Of Sites

3

Number Of Participants

60

Primary sponsor

Full Name

Universitaetsklinikum Heidelberg AöR

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Germany