Tolerability and Efficacy of Anakinra in patients with cystic fibrosis.

• Register: EUCTR
• Last refreshed on: 26 February 2024
• Main ID: EUCTR2016-004786-80-DE
• Date of registration: 30/06/2017
• Prospective Registration: Yes
• Primary sponsor: Ruprecht-Karls-University Heidelberg, Medical Faculty
• Public title: Tolerability and Efficacy of Anakinra in patients with cystic fibrosis.
• Scientific title: A phase IIa, randomized, placebo-controlled, double-blind, cross-over study to evaluate safety and efficacy of subcutanous administration of anakinra in patients with cystic fibrosis. - ANAKIN
• Date of first enrolment: 20/02/2019
• Target sample size: 52
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-004786-80
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: yes Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Germany

Contacts

• Name: Division of Pediatric Pulmonology
• Affiliation: University Hospital Heidelberg, Department of Pediatrics III

• Name: Division of Pediatric Pulmonology
• Affiliation: University Hospital Heidelberg, Department of Pediatrics III

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,
3. Sufficient fluency in German language,
4. Confirmed diagnosis of cystic fibrosis,
6. FEV1 = 50 % pred. at screening,
7.LCl 2.5 = 7.05 at screening,
8. Ability to performed study specific procedures,
9. Oxyhaemoglobin saturation of = 90% on room air at screening,
10. No recent changes in the medication for cystic fibrosis lung disease,
11. Adequate bone marrow function,
12. Adequate liver function,
13. Adequate blood clotting,
14. Negative serology for HIV, HBV, and HCV, negative Interferon-gamma release assay,
15. Negative pregnancy test in women of childbearing potential,
16. Use of adequate contraception in sexually active female subjects.
Are the trial subjects under 18? yes
Number of subjects for this age range: 27
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 25
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Expected non-compliance,
2. Known allergy to anakinra or any ingredient of the pharmaceutical formulation of Kineret®,
3. Planned (during the treatment) or recently completed immunization with attenuated (live) vaccine(s),
4. Renal failure,
5. History of tuberculosis or repeated detection of non-tuberculous mycobacteria from airway samples in the last 12 months,
6. History of detection of Burkholderia cenocepacia species in the last 12 months,
7. Colonization with multi-resistant Staphylococcus aureus (MRSA) and/or 4-multi-resistant gram negative (MRGN) Pseudomonas aeruginosa,
8. Acute bronchopulmonary exacerbation,
9. Signs of other active infection within 14 days prior to the screening,
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. Recent Participation in another interventional trial,
12. Current oral corticosteroid use,
13. Current oxygen supplementation,
14. Current treatment with etanercept,
15. Medical history of lung transplantation,
16. Pregnancy or nursing,
17. Known hypersensitivity to hypertonic saline (used for induction of sputum).


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Cystic fibrosis
MedDRA version: 20.0 Level: LLT Classification code 10028141 Term: Mucoviscidosis System Organ Class: 100000004850

Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

Intervention(s)

Trade Name: Kineret
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: ANAKINRA
CAS Number: 143090-92-0
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 150-
Pharmaceutical form of the placebo: Solution for injection in pre-filled syringe
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: At all trial visits, i.e. at 6 timepoints: Screening visit, directly prior and directly after administration of IMP and Placebo, End of trial visit.

Primary end point(s): • Absolute pre-post change of the lung clearance index (LCI).

Secondary Objective: • Evaluation of the safety and tolerability of the 28-days-treatment with anakinra.
• Investigation of the effects of anakinra on lung function.
• Evaluation of the impact of anakinra on the quality-of-life (QoL).

Main Objective: • Assessment of absolute pre-post change of the lung clearance index (LCI).

Secondary Outcome(s)

Secondary end point(s): • 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
• 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).
• 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).
• 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).

Substudies:
• Assessment of the influence of anakinra on lung structure and perfusion determined by chest MRI.
• Assessment of the influence of anakinra on airway inflammation by means of the following parameters:
o Absolute and differential cell count in sputum samples,
o Inflammatory markers in sputum samples.
• Assessment of the influence of anakinra on the bronchial infection status by means of sputum microbiology.

Timepoint(s) of evaluation of this end point: At all trial visits, i.e. at 6 timepoints: Screening visit, directly prior and directly after administration of IMP and Placebo, End of trial visit.

Secondary ID(s)

ANAKIN

Source(s) of Monetary Support

BMBF

Ethics review

Status: Approved
Approval date: 20/02/2019
Contact: