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

• 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: Novartis
• Information provided by (Responsible Party): Novartis

Tracking Information

• First Submitted Date: April 25, 2007
• First Posted Date: April 27, 2007
• Results First Submitted Date: November 16, 2010
• Results First Posted Date: February 11, 2011
• Last Update Posted Date: August 28, 2017
• Study Start Date: April 2007
• Actual Primary Completion Date: October 2008 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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 (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

Current Secondary Outcome Measures (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 (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: Efficacy, Safety, and Tolerability of ACZ885 in Patients With Muckle-Wells Syndrome
• 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

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: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Muckle Wells Syndrome

Intervention

• Drug: ACZ885
• Drug: Placebo

Study Arms

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

Publications *

• Kone-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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 17, 2011): 35
• Original Enrollment (submitted: April 25, 2007): 20
• Study Completion Date: Not Provided
• Actual Primary Completion Date: October 2008 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 4 Years to 75 Years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: France, Germany, India, Spain, United Kingdom, United States

Administrative Information

• NCT Number: NCT00465985
• Other Study ID Numbers: CACZ885D2304
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Novartis
• Original Responsible Party: Not Provided
• Current Study Sponsor: Novartis
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Novartis
• Verification Date: July 2017