Ilaris® (canakinumab) efficacy and safety in CAPS patients without confirmed mutation on exon 3 of gene CIAS1 and young (<2yrs) CAPS patients with severe neurological (CINCA) phenotype.

Conditions: Cryopyrin-Associated Periodic Syndromes
MedDRA version: 17.1Level: PTClassification code 10068850Term: Cryopyrin associated periodic syndromeSystem Organ Class: 10010331 - Congenital, familial and genetic disorders
Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Registration Number: EUCTR2014-001393-34-BE

Lead Sponsor: Z Leuven

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: Not specified

Inclusion Criteria

1. Male or female adults, adolescents and children aged 2 years and older with body weight of 7.5 kg or above. Younger (<2 yrs) patients with CINCA phenotype and central nervous system involvement will be included as soon as diagnosis is confirmed.
2. Patients and/or their legally authorized representative(s) who have agreed to participate and have signed the informed consent
3. Patients with the diagnosis of CAPS based upon the clinical and biological phenotype, and the opinion of the treating expert physician including: CRP > 10 mg/ l (confirmed by a lab protocol) and at least one of the following clinical manifestations:
o General symptoms: fever, headache, fatigue, anemia
o Skin: rash/non-pruritic urticaria
o Osteo-articular system: arthralgia, arthritis, bone malformations
o Ophtalmological problems: retinitis, conjunctivitis, uveitis, papilledema ; Progressive deafness (following cochlear nerve damage)
o Neurological involvement: due to chronic inflammation: chronic aseptic meningitis, cerebral atrophy, intracranial hypertension, ventricle dilatation, calcification, papilledema
o Renal dysfunction following AA amyloidosis
4. For patients aged 2 years and older: no mutation confirmed on exon 3 of gene CIAS-1, following standard genetic mutation analysis.

Are the trial subjects under 18? yes
Number of subjects for this age range: 3
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Pregnant or breastfeeding women.
2. Participation in any clinical trial investigation within 4 weeks prior to dosing or longer if
required by local regulation.
3. In case of previous treatment with biologic agents or DMARDs, an appropriate washout
period (as according to the recognized duration of effect and half-lives)
4. History of immunological compromisation.
5. Positive test for or prior history of HIV (ELISA and Western blot), Hepatitis B (Hepatitis B surface antigen) or Hepatitis C.
6. 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.
7. 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.
8. History of malignancy except for treated basal cell carcinoma
9. History of recurrent and/or evidence of active bacterial, fungal or viral infection(s).
10. 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.
11. Patients with neutropenia (absolute neutrophil count [ANC] < 1.5 x 109/l)
12. History of significant medical conditions, which in the investigator’s opinion would exclude the patient from participating in this trial.
13. Other Interleukin-1 therapy

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: • To evaluate if canakinumab at labeled dosing can induce and maintain clinical and biological remission in mutation-negative CAPS patients as well as in young (<2yrs) CAPS patients with CINCA phenotype;Secondary Objective: • To evaluate the effect of canakinumab treatment on disease activity of CAPS<br>• To assess the changes in CRP levels during the treatment period<br>• To evaluate the safety of canakinumab in mutation-negative CAPS patients as well as in young (<2yrs) CAPS patients with CINCA phenotype.<br>;Primary end point(s): Response will be defined as follows (all criteria to be fulfilled): Physician global assessment of auto-inflammatory disease activity = minimal (using a 5-pointscale ranging from absent to severe) AND assessment of skin disease = minimal (using a 5-point scale ranging from absent to severe) AND serological response: Serum C-reactive protein (CRP) < 10 mg/L.;Timepoint(s) of evaluation of this end point: every 8 weeks from week 8 till week104

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): * Physician global assessment of auto-inflammatory disease activity = minimal (using a 5-pointscale ranging from absent to severe)<br>* assessment of skin disease = minimal (using a 5-point scale ranging from absent to severe)<br>* serological response: Serum C-reactive protein (CRP) < 10 mg/L.;Timepoint(s) of evaluation of this end point: every 8 weeks from week 8 till week104