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

History of Changes

Tracking Information
First Received Date ^ICMJE	April 25, 2007
Last Updated Date	July 31, 2012
Start Date ^ICMJE	April 2007
Primary Completion Date	October 2008 (final data collection date for primary outcome measure)
Current Primary Outcome Measures ^ICMJE (submitted: January 17, 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 ] [ 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.
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	Complete list of historical versions of study NCT00465985 on ClinicalTrials.gov Archive Site
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 ] [ 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 ]
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 Outcome Measures ^ICMJE	Not Provided
Original Other Outcome Measures ^ICMJE	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	Phase 3
Study Design ^ICMJE	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Condition ^ICMJE	Muckle Wells Syndrome
Intervention ^ICMJE	Drug: ACZ885 Drug: Placebo
Study Arm (s)	Experimental: Part I, Part II-arm1, & Part III Intervention: Drug: ACZ885 Placebo Comparator: Part II - arm 2 Intervention: Drug: Placebo
Publications *	Koné-Paut I, Lachmann HJ, Kuemmerle-Deschner JB, Hachulla E, Leslie KS, Mouy R, Ferreira A, Lheritier K, Patel N, Preiss R, Hawkins PN; Canakinumab in CAPS Study Group. Sustained remission of symptoms and improved health-related quality of life in patients with cryopyrin-associated periodic syndrome treated with canakinumab: results of a double-blind placebo-controlled randomized withdrawal study. Arthritis Res Ther. 2011;13(6):R202. Epub 2011 Dec 9. Lachmann HJ, Kone-Paut I, Kuemmerle-Deschner JB, Leslie KS, Hachulla E, Quartier P, Gitton X, Widmer A, Patel N, Hawkins PN; Canakinumab in CAPS Study Group. Use of canakinumab in the cryopyrin-associated periodic syndrome. N Engl J Med. 2009 Jun 4;360(23):2416-25.
* 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
Enrollment ^ICMJE	35
Completion Date	Not Provided
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
Gender	Both
Ages	4 Years to 75 Years
Accepts Healthy Volunteers	No
Contacts ^ICMJE	Contact information is only displayed when the study is recruiting subjects
Location Countries ^ICMJE	United States, France, Germany, India, Spain, United Kingdom

Administrative Information
NCT Number ^ICMJE	NCT00465985
Other Study ID Numbers ^ICMJE	CACZ885D2304
Has Data Monitoring Committee	Not Provided
Responsible Party	Novartis
Study Sponsor ^ICMJE	Novartis
Collaborators ^ICMJE	Not Provided
Investigators ^ICMJE	Not Provided
Information Provided By	Novartis
Verification Date	July 2012
^ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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