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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00465985
Recruitment Status : Completed
First Posted : April 27, 2007
Results First Posted : February 11, 2011
Last Update Posted : August 28, 2017
Sponsor:
Information provided by (Responsible Party):
Novartis

Tracking Information
First Submitted Date  ICMJE April 25, 2007
First Posted Date  ICMJE April 27, 2007
Results First Submitted Date  ICMJE November 16, 2010
Results First Posted Date  ICMJE February 11, 2011
Last Update Posted Date August 28, 2017
Study Start Date  ICMJE April 2007
Actual Primary Completion Date October 2008   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 20, 2011)
  • 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 Measures  ICMJE
 (submitted: April 25, 2007)
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
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 20, 2011)
  • 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 Measures  ICMJE
 (submitted: April 25, 2007)
  • 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
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Efficacy, Safety, and Tolerability of ACZ885 in Patients With Muckle-Wells Syndrome
Official Title  ICMJE 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
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 Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Muckle Wells Syndrome
Intervention  ICMJE
  • Drug: ACZ885
  • Drug: Placebo
Study Arms  ICMJE
  • Experimental: Part I, Part II-arm1, & Part III
    Intervention: Drug: ACZ885
  • Placebo Comparator: Part II - arm 2
    Intervention: Drug: Placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 17, 2011)
35
Original Enrollment  ICMJE
 (submitted: April 25, 2007)
20
Study Completion Date  ICMJE Not Provided
Actual Primary Completion Date October 2008   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 4 Years to 75 Years   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France,   Germany,   India,   Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00465985
Other Study ID Numbers  ICMJE CACZ885D2304
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Novartis
Study Sponsor  ICMJE Novartis
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Novartis
Verification Date July 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP