Muckle-Wells Syndrome: rare hereditary, autosomal dominant, systemic inflammatory disease, characterized by recurrent episodes of fever, arthralgia, myalgia, urticarial rash, and conjunctivitis. Laboratory findings show an elevation of acute phase proteins such as CRP and SAA, a high ESR, together with leukocytosis, and hypergammaglobulinemia. Severe long term complications include progressive sensorineural deafness, and in systemic AA amyloidosis.
Conditions
Interventions
Product Code: ACZ885
Pharmaceutical Form: Powder and solvent for solution for injection
Current Sponsor code: ACZ885
Other descriptive name: ACZ885 drug substance
Concentration unit: mg milligram(s)
C
Sponsors
Novartis Pharma Services AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male and female patients aged 4 to 75 years (inclusive) at the time of the screening visit, having passed screening examinations. 2. Female subjects of child-bearing potential may participate if they have a negative pregnancy test at screening and prior to dosing, and are willing to use, if adequate for age, an effective method of contraception (e.g. birth control pills, abstinence, double-barrier contraception, etc.) during the study (from the date of screening) and for at least 3 months following the last dose. 3. Molecular diagnosis of NALP3 mutations and clinical picture resembling MWS/ FCAS/ NOMID requiring medical intervention being either untreated or insufficiently treated. 4. Molecular diagnosis of NALP3 mutations and documented history of a clinical picture resembling MWS/FCAS/NOMID. Patients under anakinra therapy or any other IL-1 blocking therapy being in complete remission and willing to discontinue anakinra/IL-1 blocking therapy until a clinical picture of the disease (relapse) becomes evident. 5. Patients with a very severe phenotype requiring stable doses of oral prednisone (= 0.4 mg/kg/day or = 20 mg/day, whichever is lower) for at least one week prior to the screening visit. Steroid therapy may be tapered during treatment with ACZ885 at the discretion of the investigator. 6. Body weight = 12 kg and =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Participation in any clinical investigation within 4 weeks prior to dosing or longer if required by local regulation with the exception of trials with anakinra. 2. Antiinflammatory therapy with colchicine, chlorambucil, dapsone, azathioprine, mycophenolate mofetil, within 3 weeks prior to dosing. In case patients have been treated with therapeutic antibodies (e.g. anti-TNF-alpha antibodies), discontinuation of this therapy is required at least 60 days before dosing. 3. Donation or loss of 400 mL or more of blood within 8 weeks prior to dosing. 4. A past medical history of clinically significant ECG abnormalities or a family history of a prolonged QT-interval syndrome. 5. History of immunocompromise, including a positive HIV (ELISA and Western blot) test result. 6. A positive Hepatitis B surface antigen (HBsAg) or Hepatitis C test result. 7. History of drug or alcohol abuse within the 12 months prior to dosing. 8. No active medical condition such as infection, poorly controlled diabetes etc. 9. No history of tuberculosis.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the efficacy of ACZ885 administered as intravenous infusion (original protocol) and subcutaneous injection (current amendment) to improve the clinical status of patients with NALP3 (CIAS1, PYPAF1) mutations.;Secondary Objective: • To assess the safety, tolerability and immunogenicity of ACZ885 administered as intravenous infusion and subcutaneous injection in patients with NALP3 (CIAS1, PYPAF1) mutations. • To evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) of ACZ885 administered as intravenous infusion and subcutaneous injection in patients with NALP3 (CIAS1, PYPAF1) mutations. • To conduct exploratory genomic studies to identify gene expression patterns of blood that are associated with treatment response to ACZ885, or that possibly correlate with the severity or progression of autoinflammatory diseases. • To assess the efficacy of ACZ885 to modify disease progression with regards to deafness, kidney function, neurological and ophthalmological symptoms. • To assess the efficacy of ACZ885 to modify health-related quality of life.;Primary end point(s): To determine the efficacy of ACZ885 administered as intravenous infusion (original protocol) and subcutaneous injection (current adminstration) to improve the clinical status of patients with NALP3 (CIAS1, PYPAFI). | — |
Countries
France, Germany, Spain, United Kingdom
Outcome results
None listed