Muckle-Wells Syndrome (Autoinflammatory Disease) MedDRA version: 9.1 Level: LLT Classification code 10064569 Term: Muckle-Wells syndrome
Conditions
Interventions
Product Code: ACZ885
Pharmaceutical Form: Powder and solvent for solution for injection
INN or Proposed INN: Canakinumab - proposed
Current Sponsor code: ACZ885
Concentration unit: mg milligram(s)
Con
Sponsors
Novartis Pharma Services AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: From the complete list of the protocol: Molecular diagnosis of NALP3 mutations and clinical picture resembling MWS. Male and female patients aged 4 to 75 years at the time of the screening visit. For patients under anakinra therapy or any other investigational IL-1 blocking therapy, willingness to discontinue the treatment. Are the trial subjects under 18? yes 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 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: From the complete list of the protocol: Use of the following therapies: • Etanercept in the 4 weeks prior to the baseline visit (Day 1) • Adalimumab in the 8 weeks prior to the baseline visit (Day 1) • Infliximab in the 12 weeks prior to the baseline visit (Day 1) • Any other investigational biologics in the 8 weeks prior to the baseline visit (Day 1) (with the exception of anakinra therapy and IL-1 blocking therapies –see below) • Patients who are on IL-1 blocking biological therapies (including anakinra therapy) need to discontinue this treatment. As soon as the criteria for relapse are fulfilled, patients can enter the study and receive ACZ885 treatment. This run-in phase reduces the classical wash-out phase to a medically meaningful time and avoids unnecessary suffering for the patient in case a predefined wash-out period per protocol is too long for an individual subject. • Leflunomide in the 4 weeks prior to the baseline visit (Day 1) • Thalidomide in the 4 weeks prior to the baseline visit (Day 1) • Cyclosporine in the 4 weeks prior to the baseline visit (Day 1) • i.v. immunoglobulin (i.v. Ig) in the 8 weeks prior to the baseline visit (Day 1) • 6-Mercaptopurine, azathioprine, cyclophosphamide, or chlorambucil in the 12 weeks prior to the baseline visit (Day 1) • Colchicine, dapsone, mycophenolate mofetil in the 3 weeks prior to the baseline visit (Day 1) • Corticosteroids =20mg/day or >0.4 mg/kg, whichever applies, in the 1 week prior to the baseline visit (Day 1)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess efficacy (% of patients who relapse) of ACZ885 compared with placebo in Part II as determined by the Physician’s global assessment of autoinflammatory disease activity, assessment of skin disease and inflammation markers (C-reactive protein (CRP) and/or serum amyloid A (SAA).;Secondary Objective: To assess the safety, tolerability and immunogenicity of ACZ885. To assess overall efficacy (response rate) of ACZ885 in Part I and Part III as determined by the Physician’s global assessment of autoinflammatory disease activity, assessment of skin disease and inflammation markers. To evaluate the PK and PD of ACZ885. To assess the effect of ACZ885 on disease progression with regards to deafness, kidney function, neurological and ophthalmological symptoms.;Primary end point(s): The primary variable is the proportion of patients with disease flare in the withdrawal period (Part II). Patients who prematurely discontinue study in the withdrawal phase due to any reason will be considered as having disease flare. The primary objective of the study is to show superiority of ACZ885 compared to placebo regarding the primary variable in Part II. The two treatment groups will be compared using an exact test (based on hypergeometric probabilities) about the common odds ratio, adjusting for cohort. The null hypothesis to be tested is that the common odds ratio is equal to 1, i.e. the probability of having disease flare is the same for both groups versus the common odds ratio is not equal to 1, i.e. the probability of having disease flare is different for both groups. Exact two-sided p-value, the common odds ratio and exact 95% confidence interval for the common odds ratio will be computed. The primary analysis will be based on the ITT population of Part II. | — |
Countries
France, Germany, Spain, United Kingdom
Outcome results
None listed