Evaluating Anakinra for Cystic Fibrosis Treatment

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

This study is testing if a medication called anakinra can help improve lung function and quality of life for people aged 12 and older with cystic fibrosis.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 52 (estimated)
• Ages: 12 Years and up
• Sex: All
• Sponsor: Heidelberg University (Academic / other)
• Locations: 3 sites (Heidelberg, Baden-Wurttemberg and 2 other locations)
• Trial ID: NCT03925194 on ClinicalTrials.gov

What this trial studies

This study evaluates the safety and efficacy of subcutaneous administration of anakinra in patients aged 12 years and older with cystic fibrosis. The primary objective is to assess the treatment's effectiveness using the lung clearance index (LCI), while secondary objectives include evaluating safety, tolerability, and its impact on lung function and quality of life. Participants will undergo assessments to determine their eligibility based on specific criteria related to their cystic fibrosis diagnosis and lung function.

Who should consider this trial

Good fit: Ideal candidates are patients aged 12 years and older with a confirmed diagnosis of cystic fibrosis and specific lung function parameters.

Not a fit: Patients with less severe lung function or those not meeting the inclusion criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could improve lung function and quality of life for patients with cystic fibrosis.

How similar studies have performed: Other studies have explored treatments for cystic fibrosis, but the use of anakinra in this context is relatively novel.

Eligibility 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).

Where this trial is running

Heidelberg, Baden-Wurttemberg and 2 other locations

• University Children's Hospital Heidelberg, Cystic Fibrosis Centre — Heidelberg, Baden-Wurttemberg, Germany (Recruiting)
• Universitätsmedizin Essen, Ruhrlandklinik — Essen, North Rhine-Westphalia, Germany (Recruiting)
• Charité - Universitätsmedizin Berlin — Berlin, State of Berlin, Germany (Recruiting)

Conditions Cystic Fibrosis, 10011762