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

• Register: ClinicalTrials.gov
• Last refreshed on: 8 January 2024
• Main ID: NCT03925194
• Date of registration: 19/04/2019
• Prospective Registration: Yes
• Primary sponsor: Heidelberg University
• Public title: A Study to Evaluate Safety and Efficacy of Subcutaneous Administration of Anakinra in Patients With CF ANAKIN
• Scientific title: 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
• Date of first enrolment: December 1, 2022
• Target sample size: 52
• Recruitment status: Recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT03925194
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Crossover Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 2

Countries of recruitment

Germany

Key inclusion & exclusion criteria

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 to
comply with study-specific procedures (e.g. to complete required quality of life
questionnaires),

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

1. sweat chloride = 60mEq/L,

2. two CF causing mutations in the CFTR gene,

3. alterations of transepithelial potential difference of nasal or rectal epithelia
typical for CF,

5. FEV1 = 50 % pred. at screening,

6. LCI2.5 = 7.05 at screening,

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

8. Oxyhaemoglobin saturation of = 90% on room air at screening,

9. 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),

10. 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,

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

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

13. 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,

14. 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)),

15. 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 with study-specific
procedures,

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

3. 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,

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

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

6. History of detection of Burkholderia cenocepacia species in the last 12 months before
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 exclusion
criterion if the treating physician judges that this is an increased risk for the
patient,

8. Acute bronchopulmonary exacerbation (defined by modified Fuchs criteria (1) (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,

9. 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),

10. 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,

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

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 negative
pregnancy test at Screening),

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



Age minimum: 12 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Cystic Fibrosis, 10011762

Intervention(s)

Drug: Anakinra

Primary Outcome(s)

Absolute pre-post change of the lung clearance index (LCI) [Time Frame: 28 days]

Secondary ID(s)

EudraCT No.: 2016-004786-80-A

Source(s) of Monetary Support

Please refer to primary and secondary sponsors