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

Novartis35 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Muckle Wells Syndrome

Interventions

ACZ885DRUG

PlaceboDRUG

Eligibility

Sex: ALLMin age: 4 YearsMax age: 75 Years

Medical Language ↔ Plain English

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

Locations (12)

Novartis Investigative Site

San Francisco, California, United States

Novartis Investigative Site

Chicago, Illinois, United States

Novartis Investigative Site

Madison, Wisconsin, United States

Outcomes

Primary Outcomes

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.

Time frame: 32 weeks after study start

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.

Time frame: 32 weeks after study start

Secondary Outcomes

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.

Time frame: 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)

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

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.