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

July 28, 2017 updated by: Novartis

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

35

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Le Kremlin Bicetre, France
        • Novartis Investigative Site
      • Lille Cedex, France
        • Novartis Investigational Site
      • Montpellier Cedex, France
        • Novartis Investigative Site
      • Nantes, France
        • Novartis Investigative Site
      • Paris, France
        • Novartis Investigative Site
  • Germany
      • Tubingen, Germany
        • Novartis Investigative Site
  • India
      • New Delhi, India
        • Novartis Investigative Site
  • Spain
      • Barcelona, Spain
        • Novartis Investigative Site
  • United Kingdom
      • London, United Kingdom
        • Novartis Investigative Site
  • United States
    • California
      • San Francisco, California, United States, 94115
        • Novartis Investigative Site
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Novartis Investigative Site
    • Wisconsin
      • Madison, Wisconsin, United States, 53792
        • Novartis Investigative Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

4 years to 75 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
32 weeks after study start
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.
32 weeks after study start

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
8 weeks after study start
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
32 weeks after study start
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
Week 8 and Week 32
Pharmacokinetics (CLD (L/d))
Time Frame: 48 weeks after study start
Assessed serum clearance of ACZ885.
48 weeks after study start
Pharmacodynamics Measured by Interleukin-1β (IL-1β) Concentrations at End of Part I.
Time Frame: until Week 8
until Week 8
Pharmacodynamics Measured by Interleukin-1β (IL-1β) Concentrations at End of Part II.
Time Frame: 32 weeks after study start
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
48 weeks after study start

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Novartis

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2007

Primary Completion (Actual)

October 1, 2008

Study Registration Dates

First Submitted

April 25, 2007

First Submitted That Met QC Criteria

April 25, 2007

First Posted (Estimate)

April 27, 2007

Study Record Updates

Last Update Posted (Actual)

August 28, 2017

Last Update Submitted That Met QC Criteria

July 28, 2017

Last Verified

July 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CACZ885D2304

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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