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

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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

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Muckle Wells Syndrome	Drug: ACZ885 Drug: Placebo	Phase 3

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	35 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Quadruple (Participant, Care Provider, 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
Study Start Date :	April 2007
Actual Primary Completion Date :	October 2008

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Muckle-Wells syndrome

Drug Information available for: Canakinumab

Genetic and Rare Diseases Information Center resources: Wells Syndrome Muckle-Wells Syndrome Cryopyrin-associated Periodic Syndrome Familial Mediterranean Fever

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: Part I, Part II-arm1, & Part III	Drug: ACZ885
Placebo Comparator: Part II - arm 2	Drug: Placebo

Outcome Measures

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 ]
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 Outcome 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 ]

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	4 Years to 75 Years (Child, Adult, Older Adult)
Sexes Eligible for Study:	All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00465985

Locations

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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

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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. doi: 10.1186/ar3535. 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. doi: 10.1056/NEJMoa0810787.

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Responsible Party:	Novartis
ClinicalTrials.gov Identifier:	NCT00465985
Other Study ID Numbers:	CACZ885D2304
First Posted:	April 27, 2007 Key Record Dates
Results First Posted:	February 11, 2011
Last Update Posted:	August 28, 2017
Last Verified:	July 2017

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:

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Cellulitis Eosinophilia Cryopyrin-Associated Periodic Syndromes Syndrome Disease Pathologic Processes Skin Diseases, Infectious Infections Suppuration	Connective Tissue Diseases Inflammation Leukocyte Disorders Hematologic Diseases Hereditary Autoinflammatory Diseases Genetic Diseases, Inborn Skin Diseases, Genetic Skin Diseases

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