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

Primary Purpose

Muckle Wells Syndrome

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
ACZ885
Placebo
Sponsored by
Novartis
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Muckle Wells Syndrome focused on measuring 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

Eligibility Criteria

4 Years - 75 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigational Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Part I, Part II-arm1, & Part III

Part II - arm 2

Arm Description

Outcomes

Primary Outcome Measures

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.
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.

Secondary Outcome Measures

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.
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
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.
Pharmacokinetics (CLD (L/d))
Assessed serum clearance of ACZ885.
Pharmacodynamics Measured by Interleukin-1β (IL-1β) Concentrations at End of Part I.
Pharmacodynamics Measured by Interleukin-1β (IL-1β) Concentrations at End of Part II.
Pharmacodynamics Measured by Interleukin-1β (IL-1β) Concentrations at End of Part III.

Full Information

First Posted
April 25, 2007
Last Updated
July 28, 2017
Sponsor
Novartis
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1. Study Identification

Unique Protocol Identification Number
NCT00465985
Brief Title
Efficacy, Safety, and Tolerability of ACZ885 in Patients With Muckle-Wells Syndrome
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
July 2017
Overall Recruitment Status
Completed
Study Start Date
April 2007 (undefined)
Primary Completion Date
October 2008 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis

4. Oversight

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Muckle Wells Syndrome
Keywords
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
35 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Part I, Part II-arm1, & Part III
Arm Type
Experimental
Arm Title
Part II - arm 2
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
ACZ885
Intervention Type
Drug
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
Percent of Participants With Disease Flare in Part II (After 24 Weeks of the Double-blind Part)
Description
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.
Time Frame
32 weeks after study start
Title
Number of Participants Who Experienced a Disease Flare in Part II
Description
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.
Time Frame
32 weeks after study start
Secondary Outcome Measure Information:
Title
Number of Participants With Treatment Response in Part I (After 8 Weeks)
Description
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.
Time Frame
8 weeks after study start
Title
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)
Description
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
Time Frame
32 weeks after study start
Title
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
Title
Pharmacokinetics (CLD (L/d))
Description
Assessed serum clearance of ACZ885.
Time Frame
48 weeks after study start
Title
Pharmacodynamics Measured by Interleukin-1β (IL-1β) Concentrations at End of Part I.
Time Frame
until Week 8
Title
Pharmacodynamics Measured by Interleukin-1β (IL-1β) Concentrations at End of Part II.
Time Frame
32 weeks after study start
Title
Pharmacodynamics Measured by Interleukin-1β (IL-1β) Concentrations at End of Part III.
Time Frame
48 weeks after study start

10. Eligibility

Sex
All
Minimum Age & Unit of Time
4 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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
Facility Information:
Facility Name
Novartis Investigative Site
City
San Francisco
State/Province
California
ZIP/Postal Code
94115
Country
United States
Facility Name
Novartis Investigative Site
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
Novartis Investigative Site
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53792
Country
United States
Facility Name
Novartis Investigative Site
City
Le Kremlin Bicetre
Country
France
Facility Name
Novartis Investigational Site
City
Lille Cedex
Country
France
Facility Name
Novartis Investigative Site
City
Montpellier Cedex
Country
France
Facility Name
Novartis Investigative Site
City
Nantes
Country
France
Facility Name
Novartis Investigative Site
City
Paris
Country
France
Facility Name
Novartis Investigative Site
City
Tubingen
Country
Germany
Facility Name
Novartis Investigative Site
City
New Delhi
Country
India
Facility Name
Novartis Investigative Site
City
Barcelona
Country
Spain
Facility Name
Novartis Investigative Site
City
London
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
22152723
Citation
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.
Results Reference
derived
PubMed Identifier
19494217
Citation
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.
Results Reference
derived

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

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