Efficacy and Safety Study of ACZ885 in Patients With Active Recurrent or Chronic TNF-receptor Associated Periodic Syndrome (TRAPS).
Condition: TNF-receptor Associated Periodic Syndromes (TRAPS)
MeSH terms: Hereditary Autoinflammatory Diseases; Syndrome; Fever
Intervention: ACZ885
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 20.0
Sex: All
Minimum age: 4 Years
Healthy volunteers: No
Keywords: TNF-receptor associated periodic syndrome; fevers; rashes; musculoskeletal and abdominal pain; periorbital edema; TNFR1

Summary:

      This trial will assess the safety and efficacy of ACZ885 in patients with active recurrent or
      chronic TNF-receptor associated periodic syndrome (TRAPS).
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patient's written informed consent for >or= 18 years of age before any assessment is
             performed. Parent or legal guardian's written informed consent and child's assent, if
             appropriate, are required before any assessment is performed for patients < 18 years
             of age.

          2. Male and female patients at least 4 years of age at the time of the screening visit.

          3. Patients with a clinical diagnosis of TRAPS and a mutation of TNFRSF1A gene. Patients
             with low penetrance mutations, such as R92Q or P46L, can be included with mutual
             agreement between the investigator and Novartis.

          4. Patients with a diagnosis of recurrent TRAPS must experience more than 6 episodes/year
             prior to receiving an effective biologic therapy and the duration of each episode
             lasted at least 8 days. For patients receiving biologic therapy, this criterion
             applies to prior to receiving the biologic therapy.

          5. Patients who have been treated with anakinra must have demonstrated a partial or
             complete clinical response with an associated decrease in their inflammation markers
             (CRP and SAA).

          6. Active TRAPS as evidenced by clinical signs and symptoms of active TRAPS (Physician's
             Global Assessment >or= 2) and an elevated CRP > 10mg/L (Normal CRP range <or= 10 mg/L)
             and/or SAA > 10 mg/L (Normal SAA range <or= 10 mg/L) at time of first canakinumab
             treatment.

        Exclusion Criteria:

          1. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a
             female after conception and until the termination of gestation, confirmed by a
             positive hCG laboratory test (> 5 mIU/mL).

          2. Women of child-bearing potential, defined as pre-menarche females aged 8 years and
             above or all women physiologically capable of becoming pregnant, UNLESS they are

               -  women whose career, lifestyle, or sexual orientation precludes intercourse with a
                  male partner

               -  women whose partners have been sterilized by vasectomy or other means

               -  using a highly effective method of birth control (i.e. one that results in a less
                  than 1% per year failure rate when used consistently and correctly, such as
                  implants, injectables, combined oral contraceptives, and some intrauterine
                  devices [IUDs]; periodic abstinence [e.g. calendar, ovulation, symptothermal,
                  post-ovulation methods] is not acceptable) or total abstinence at the discretion
                  of the investigator in cases where the age, career, lifestyle, or sexual
                  orientation of the patient ensures compliance.

               -  Women of child-bearing potential should be willing to use a reliable
                  contraception throughout the study and for 3 months after study drug
                  discontinuation.

               -  Women are considered post-menopausal and not of child bearing potential if they
                  have had 12 months of natural (spontaneous) amenorrhea with an appropriate
                  clinical profile (e.g. age appropriate, history of vasomotor symptoms) or six
                  months of spontaneous amenorrhea with serum FSH levels > 40 mIU/mL or have had
                  surgical bilateral oophorectomy (with or without hysterectomy) at least six weeks
                  ago. In the case of oophorectomy alone, only when the reproductive status of the
                  woman has been confirmed by follow up hormone level assessment is she considered
                  not of child bearing potential.

          3. History of being immunocompromised, including a positive HIV at screening (ELISA and
             Western blot) test result.

          4. Positive QuantiFERON (QFT-TB G In-Tube) test or positive Purified Protein Derivative
             (PPD) test (>or= 5 mm induration) at screening or within 2 month prior to the
             screening visit, according to the national guidelines. Patients with a positive PPD
             test (>or= 5 mm induration) at screening may be enrolled only if they have either a
             negative chest x-ray or a negative QuantiFERON test.

          5. Live vaccinations within 3 months prior to the start of the trial, during the trial,
             and up to 3 months following the last dose.

          6. History of significant other medical conditions, which in the Investigator's opinion
             would exclude the patient from participating in this trial.

          7. History of recurrent and/or evidence of active bacterial, fungal, or viral
             infection(s).

          8. Use of prohibited therapies, any other investigational biologics within 8 weeks prior
             to the Baseline visit, any other investigational drugs, other than investigational
             biologic treatment, within 30 days (or 3 months for investigational monoclonal
             antibodies) or 5 half-lives prior to the Baseline visit, whichever is longer

          9. History of known hypersensitivity to canakinumab.

         10. History of malignancy of any organ system (other than localized basal cell carcinoma
             of the skin), treated or untreated, within the past 5 years, regardless of whether
             there is evidence of local recurrence or metastases

        Other protocol defined inclusion/exclusion criteria may apply.