E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Cystic fibrosis, mucoviscidosis |
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E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10028141 |
E.1.2 | Term | Mucoviscidosis |
E.1.2 | System Organ Class | 100000004850 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
• Assessment of absolute pre-post change of the lung clearance index (LCI). |
|
E.2.2 | Secondary objectives of the trial |
• 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). |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Both sub-studies are described directly in the main trial protocol. Their objectives are: • Assessment of the influence of anakinra on lung structure and perfusion. • Assessment of the influence of anakinra on airway inflammation and bronchial infection |
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E.3 | Principal 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. |
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E.4 | Principal 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). |
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E.5 End points |
E.5.1 | Primary end point(s) |
• Absolute pre-post change of the lung clearance index (LCI). |
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E.5.1.1 | 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. |
|
E.5.2 | 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. |
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E.5.2.1 | 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. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |