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

Muckle Wells Syndrome Clinical Trial

— REMITTER  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00465985
• Other study ID #: CACZ885D2304
• Status: Completed
• Phase: Phase 3
• First received: April 25, 2007
• Last updated: July 31, 2012
• Start date: April 2007

Study information

• Verified date: July 2012
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationGermany: Paul Ehrlich InstituteSpain: Spanish Agency of MedicinesFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)United Kingdom: Medicines and Healthcare Products Regulatory AgencyIndia: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 35
• Est. primary completion date: October 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 4 Years to 75 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cellulitis
• Cryopyrin-Associated Periodic Syndromes
• Eosinophilia
• Muckle Wells Syndrome
• Syndrome

Intervention

Drug:
• ACZ885

• Placebo

Locations

Country	Name	City	State
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
Germany	Novartis Investigative Site	Tubingen
India	Novartis Investigative Site	New Delhi
Spain	Novartis Investigative Site	Barcelona
United Kingdom	Novartis Investigative Site	London
United States	Novartis Investigative Site	Chicago	Illinois
United States	Novartis Investigative Site	Madison	Wisconsin
United States	Novartis Investigative Site	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
Novartis

Countries where clinical trial is conducted

United States,  France,  Germany,  India,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent of Participants With Disease Flare in Part II (After 24 Weeks of the Double-blind Part)	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.	32 weeks after study start	No
Primary	Number of Participants Who Experienced a Disease Flare in Part II	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.	32 weeks after study start	No
Secondary	Number of Participants With Treatment Response in Part I (After 8 Weeks)	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.	8 weeks after study start	No
Secondary	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)	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	32 weeks after study start	No
Secondary	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.		Week 8 and Week 32	No
Secondary	Pharmacokinetics (CLD (L/d))	Assessed serum clearance of ACZ885.	48 weeks after study start	No
Secondary	Pharmacodynamics Measured by Interleukin-1ß (IL-1ß) Concentrations at End of Part I.		until Week 8	No
Secondary	Pharmacodynamics Measured by Interleukin-1ß (IL-1ß) Concentrations at End of Part II.		32 weeks after study start	No
Secondary	Pharmacodynamics Measured by Interleukin-1ß (IL-1ß) Concentrations at End of Part III.		48 weeks after study start	No