E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
hereditary autoinflammatory disease with MEFV mutation and inflammasome activation |
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E.1.1.1 | Medical condition in easily understood language |
a hereditary chronic condition caused by a specific mutation (in the MEFV gene) with uncontrolled inflammatory manifestations. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Primary:
1. Control of inflammatory symptoms (cutaneous, articular, muscular) and of systemic inflammation (anemia, acute phase reactants).
2. Proof of concept that the novel MEFV mutation identified in this family, causes inflammasome and caspase-1activation with increased release of IL-1.
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E.2.2 | Secondary objectives of the trial |
Demonstration of safety (clinical and laboratory i.e. hematology, blood chemistry) of Anakinra treatment in patients with a novel pyrin-associated auto inflammatory disease. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Adult patients with a hereditary autoinflammatory syndrome and S242R MEFV mutation, manifesting active disease both clinically (cutaneous and articular inflammation) and biologically (increased acute phase reactants). |
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E.4 | Principal exclusion criteria |
1. Patients with underlying active infectious disorder, and/or visceral organ involvement constituting a potential risk according to the investigator, will be excluded
2. Treatment with biological agents (esp. TNF antagonists) is not allowed during the trial, they will be stopped as follows:
Infliximab therapy will be stopped at least 8 weeks, and adalimumab/Etanercept will be stopped at least 4 weeks prior to baseline visit and first treatment with Anakinra
3. Treatment with classical DMARDS (esp. methotrexate and cyclosporine) is not allowed during the trial and will be stopped at least 4 weeks prior to baseline/first treatment with Anakinra
4. Corticosteroids are not allowed except for low-dose corticosteroids (<= 10mg prednisone equivalent daily) which can be kept stable during the trial.
5. Pregnant or breastfeeding women.
6. Participation in any clinical trial investigation within 4 weeks prior to dosing or longer if
required by local regulation.
7. Positive test for or prior history of HIV (ELISA and Western blot), Hepatitis B (Hepatitis B surface antigen) or Hepatitis C.
8. Presence of active infections or a history of pulmonary TB infection with or without
documented adequate therapy. Subjects with current active TB, or recent close exposure to an individual with active TB are excluded from the study.
9. Treatment with a live virus vaccine during 3 months prior to baseline visit. No live vaccines were allowed throughout the course of this study and up to 3 months following the last dose.
10. History of malignancy except for treated basal cell carcinoma
11. History of recurrent and/or evidence of active bacterial, fungal or viral infection(s).
12. Presence of any of the following laboratory abnormalities: ALT or AST greater than 2 times the upper limit of normal (ULN), platelet count less than 100x109/L.
13. Patients with neutropenia (absolute neutrophil count [ANC] < 1.5 x 109/l)
14. History of significant medical conditions, which in the investigator’s opinion would exclude the patient from participating in this trial.
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E.5 End points |
E.5.1 | Primary end point(s) |
1. A comprehensive and detailed study of clinical features (cutaneous, articular, muscular) and laboratory parameters of inflammation (ESR, CRP, complete blood cell count) will be performed at baseline and each study visit according to a standardized protocol.
2. In vitro testing of inflammasome activation will be performed on patient’s blood samples at baseline, at 2 and 4 weeks, as well as at 12 weeks of Anakinra treatment.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
baseline, week 2, week 4, week 8 and week 12 |
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E.5.2 | Secondary end point(s) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
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 | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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 | No |
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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week 12, with possible extension to week 52 depending on efficacy data on week 12 |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |