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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis
ClinicalTrials.gov Identifier:
NCT00465985
First received: April 25, 2007
Last updated: July 31, 2012
Last verified: July 2012
  Purpose

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.


Condition Intervention Phase
Muckle Wells Syndrome
Drug: ACZ885
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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 Antibody)in Patients With Muckle-Wells Syndrome

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome 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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 Outcome Measures:
  • Number of Participants With Treatment Response in Part I (After 8 Weeks) [ Time Frame: 8 weeks after study start ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]
  • Pharmacokinetics (CLD (L/d)) [ Time Frame: 48 weeks after study start ] [ Designated as safety issue: No ]
    Assessed serum clearance of ACZ885.

  • Pharmacodynamics Measured by Interleukin-1β (IL-1β) Concentrations at End of Part I. [ Time Frame: until Week 8 ] [ Designated as safety issue: No ]
  • Pharmacodynamics Measured by Interleukin-1β (IL-1β) Concentrations at End of Part II. [ Time Frame: 32 weeks after study start ] [ Designated as safety issue: No ]
  • Pharmacodynamics Measured by Interleukin-1β (IL-1β) Concentrations at End of Part III. [ Time Frame: 48 weeks after study start ] [ Designated as safety issue: No ]

Enrollment: 35
Study Start Date: April 2007
Primary Completion Date: October 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part I, Part II-arm1, & Part III Drug: ACZ885
Placebo Comparator: Part II - arm 2 Drug: Placebo

  Eligibility

Ages Eligible for Study:   4 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00465985

Locations
United States, California
Novartis Investigative Site
San Francisco, California, United States, 94115
United States, Illinois
Novartis Investigative Site
Chicago, Illinois, United States, 60612
United States, Wisconsin
Novartis Investigative Site
Madison, Wisconsin, United States, 53792
France
Novartis Investigative Site
Le Kremlin Bicetre, France
Novartis Investigational Site
Lille Cedex, France
Novartis Investigative Site
Montpellier Cedex, France
Novartis Investigative Site
Nantes, France
Novartis Investigative Site
Paris, France
Germany
Novartis Investigative Site
Tubingen, Germany
India
Novartis Investigative Site
New Delhi, India
Spain
Novartis Investigative Site
Barcelona, Spain
United Kingdom
Novartis Investigative Site
London, United Kingdom
Sponsors and Collaborators
Novartis
  More Information

No publications provided by Novartis

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Novartis
ClinicalTrials.gov Identifier: NCT00465985     History of Changes
Other Study ID Numbers: CACZ885D2304
Study First Received: April 25, 2007
Results First Received: November 16, 2010
Last Updated: July 31, 2012
Health Authority: United States: Food and Drug Administration
Germany: Paul Ehrlich Institute
Spain: Spanish Agency of Medicines
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
United Kingdom: Medicines and Healthcare Products Regulatory Agency
India: Ministry of Health

Keywords provided by Novartis:
Muckle-Wells Syndrome
children
systemic autoinflammatory disease
CIAS-1 gene
NALP-3
ACZ885
human monoclonal anti-human interleukin-1beta (IL-1beta)
antibody
autosomal dominant
familial autoinflammatory syndrome

Additional relevant MeSH terms:
Hereditary Autoinflammatory Diseases
Cryopyrin-Associated Periodic Syndromes
Cellulitis
Eosinophilia
Genetic Diseases, Inborn
Skin Diseases, Genetic
Skin Diseases
Skin Diseases, Infectious
Infection
Suppuration
Connective Tissue Diseases
Inflammation
Pathologic Processes
Leukocyte Disorders
Hematologic Diseases

ClinicalTrials.gov processed this record on August 20, 2014