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

Overview

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.

Full Title of Study: “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 Antibody)in Patients With Muckle-Wells Syndrome”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  • Study Primary Completion Date: October 2008

Interventions

  • Drug: ACZ885
  • Drug: Placebo

Arms, Groups and Cohorts

  • Experimental: Part I, Part II-arm1, & Part III
  • Placebo Comparator: Part II – arm 2

Clinical Trial Outcome Measures

Primary Measures

  • 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.

Secondary Measures

  • 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

Participating in This Clinical Trial

Inclusion Criteria

  • Molecular diagnosis of NALP3 mutations and clinical picture resembling Muckle-Wells Syndrome. – Muckle-Wells Syndrome patients who participated in the CACZ885A2102 study, will have the option to participate in this study upon disease flare – Muckle-Wells Syndrome patients requiring medical intervention either untreated or treated (i.e. under ACZ885, anakinra, or any other investigational IL-1 blocking therapy). Exclusion Criteria:
  • History of being immunocompromised, including a positive HIV at screening test result. – No live vaccinations within 3 months prior to the start of the trial, during the trial, and up to 3 months following the last dose. – History of significant medical conditions, which in the Investigator's opinion would exclude the patient from participating in this trial. – History of recurrent and/or evidence of active bacterial, fungal, or viral infections. – Positive tuberculin skin test at 48 to 72 hours after administration at the screening visit or within 2 months prior to the screening visit, according to national guidelines. Other protocol-defined inclusion/exclusion criteria may apply
  • Gender Eligibility: All

    Minimum Age: 4 Years

    Maximum Age: 75 Years

    Are Healthy Volunteers Accepted: No

    Investigator Details

    • Lead Sponsor
      • Novartis
    • Provider of Information About this Clinical Study
      • Sponsor

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