Clinical trial NCT00465985: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: 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
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2007-04-27
Enrollment: 35
Sex: ALL
Minimum age (years): 4
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Percent of Participants With Disease Flare in Part II (After 24 Weeks of the Double-blind Part)
timeFrame: 32 weeks after study start
measure: Number of Participants Who Experienced a Disease Flare in Part II
timeFrame: 32 weeks after study start
Secondary outcomes:
measure: Number of Participants With Treatment Response in Part I (After 8 Weeks)
timeFrame: 8 weeks after study start
measure: 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)
timeFrame: 32 weeks after study start
measure: 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.
timeFrame: Week 8 and Week 32
measure: Pharmacokinetics (CLD (L/d))
timeFrame: 48 weeks after study start
measure: Pharmacodynamics Measured by Interleukin-1β (IL-1β) Concentrations at End of Part I.
timeFrame: until Week 8
measure: Pharmacodynamics Measured by Interleukin-1β (IL-1β) Concentrations at End of Part II.
timeFrame: 32 weeks after study start
measure: Pharmacodynamics Measured by Interleukin-1β (IL-1β) Concentrations at End of Part III.
timeFrame: 48 weeks after study start
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: Novartis Investigative Site
state: California
city: Chicago
country: United States
facility: Novartis Investigative Site
state: Illinois
city: Madison
country: United States
facility: Novartis Investigative Site
state: Wisconsin
city: Le Kremlin Bicetre
country: France
facility: Novartis Investigative Site
city: Lille Cedex
country: France
facility: Novartis Investigational Site
city: Montpellier Cedex
country: France
facility: Novartis Investigative Site
city: Nantes
country: France
facility: Novartis Investigative Site
city: Paris
country: France
facility: Novartis Investigative Site
city: Tubingen
country: Germany
facility: Novartis Investigative Site
city: New Delhi
country: India
facility: Novartis Investigative Site
city: Barcelona
country: Spain
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
References:
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.
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.