Clinical Trial: Efficacy, Safety, and Tolerability of ACZ885 in Patients With Muckle-Wells Syndrome

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Three-part,Multicenter Study,With a Randomized,Double-blind,Placebo Controlled,Withdrawal Design in Part II to Assess Efficacy,Safety,and Tolerability of ACZ885(Anti-interleukin-1beta Monoclonal Ant

Brief Summary:

This study is designed to provide efficacy and safety data for ACZ885 (a fully human anti-interleukin-1beta (anti-IL-1beta) monoclonal antibody) administered as an injection subcutaneously (s.c.) in patients with Muckle-Wells Syndrome.

Part I is an 8-week open-label, active treatment period to identify ACZ885 responders.

Part II is a double-blind, placebo-controlled period to assess primarily the efficacy of ACZ885 compared to placebo.

Part III is an open-label, active treatment period where patients will receive ACZ885 every 8 weeks after withdrawal or completion of Part II.

Detailed Summary:
Sponsor: Novartis

Current Primary Outcome:

• Percent of Participants With Disease Flare in Part II (After 24 Weeks of the Double-blind Part) [ Time Frame: 32 weeks after study start ]
  Determined by the Physician's global assessment of autoinflammatory disease activity, assessment of skin disease and inflammation markers. Data expressed as a percent of participants who had experienced a flare by the end of Part II.
• Number of Participants Who Experienced a Disease Flare in Part II [ Time Frame: 32 weeks after study start ]
  Disease flare is determined by the Physician's global assessment of autoinflammatory disease activity, assessment of skin disease and inflammation markers. Disease Flare = the C-reactive protein and/or serum amyloid A (SAA) > 30 mg/L and either a PGA > minimal, or PGA equal to minimal and > minimal SD.

Original Primary Outcome: Proportion of patients with disease flare in Part II (after 24 weeks of the double-blind part) will be determined by the Physician's global assessment of autoinflammatory disease activity, assessment of skin disease and inflammation markers

Current Secondary Outcome:

• Number of Participants With Treatment Response in Part I (After 8 Weeks) [ Time Frame: 8 weeks after study start ]
  Treatment response was based on Physician's global assessment(PGA) of autoinflammatory disease activity, assessment of skin disease(SD) and serum values of C-reactive protein(CRP) and/or serum amyloid A(SAA). Complete Response (CR):PGA and SD ≤ minimal and normal CRP and/or SAA. Partial Response (PR): a reduction of CRP and/or SAA from baseline (BL) by >30% but not reaching normal values and PGA improvement from BL by at least one category. Disease flare: a CRP and/or SAA > 30 mg/L and either PGA > minimal or PGA = minimal and SD > minimal. Non-responders = no PR by Day 8 or no CR by Day 15.
• Investigator's Clinical Assessment of Autoinflammatory Disease Activity & Participant's Assessment of Symptoms at End of Part II (After 24 Weeks of the Double-blind Part) [ Time Frame: 32 weeks after study start ]

  A 5-point scale was used for the Physician's global assessment on autoinflammatory disease activity (absent, minimal, mild, moderate and severe) and for the assessment of the following items:

  • skin disease (urticarial skin rash)
  • arthralgia
  • myalgia
  • headache/migraine
  • conjunctivitis
  • fatigue/malaise
  • other symptoms related to autoinflammatory syndrome
  • other symptoms not related to autoinflammatory syndrome
• Change in Inflammation Markers at the End of Part II (C-reactive Protein and/or Serum Amyloid A) (After 24 Weeks of the Double-blind Part) From Week 8. [ Time Frame: Week 8 and Week 32 ]
• Pharmacokinetics (CLD (L/d)) [ Time Frame: 48 weeks after study start ]
  Assessed serum clearance of ACZ885.
• Pharmacodynamics Measured by Interleukin-1β (IL-1β) Concentrations at End of Part I. [ Time Frame: until Week 8 ]
• Pharmacodynamics Measured by Interleukin-1β (IL-1β) Concentrations at End of Part II. [ Time Frame: 32 weeks after study start ]
• Pharmacodynamics Measured by Interleukin-1β (IL-1β) Concentrations at End of Part III. [ Time Frame: 48 weeks after study start ]

Original Secondary Outcome:

• Treatment response in Part I (after 8 weeks of treatment) determined by the Physician's global assessment of autoinflammatory disease activity, assessment of skin disease and inflammation markers (C-reactive protein and/or serum amyloid A)
• Investigator's clinical assessment of autoinflammatory disease activity & Patient's assessment of symptoms at end of Part II (after 24 weeks of the double-blind part)
• Change in inflammation markers at the end of Part II (after 24 weeks of the double-blind part)
• Pharmacokinetics and pharmacodynamics

Dates:
Date Received: April 25, 2007
Date Started: April 2007
Date Completion:
Last Updated: July 31, 2012
Last Verified: July 2012