hereditary autoinflammatory disease with MEFV mutation and inflammasome activation
Conditions
Interventions
Trade Name: Anakinra
Product Name: Anakinra
Pharmaceutical Form: Solution for injection in pre-filled syringe
Sponsors
UZ Leuven
Eligibility
Sex/Gender
Male
Inclusion criteria
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). Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 5 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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. ;Secondary Objective: Demonstration of safety (clinical and laboratory i.e. hematology, blood chemistry) of Anakinra treatment in patients with a novel pyrin-associated auto inflammatory disease. ;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. ;Timepoint(s) of evaluation of this end point: baseline, week 2, week 4, week 8 and week 12 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): none;Timepoint(s) of evaluation of this end point: not applicable | — |
Countries
Belgium
Contacts
Public ContactWouters Carine
UZ Leuven
Outcome results
None listed