Clinical trial NCT00685373: Efficacy and Safety of ACZ885 in Patients With the Following Cryopyrin-associated Periodic Syndromes: Familial Cold Autoinflammatory Syndrome, Muckle-Wells Syndrome, or Neonatal Onset Multisystem Inflammatory Disease
Official title: An Open-label, Long-term Safety and Efficacy Study of ACZ885 (Anti-interleukin-1β Monoclonal Antibody) Administered for at Least 6 Months in Patients With the Following Cryopyrin-associated Periodic Syndromes: Familial Cold Autoinflammatory Syndrome, Muckle-Wells Syndrome, or Neonatal Onset Multisystem Inflammatory Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cryopyrin-Associated Periodic Syndromes
Familial Cold Autoinflammatory Syndrome
Muckle Wells Syndrome
Neonatal Onset Multisystem Inflammatory Disease
Keywords: Cryopyrin-associated periodic syndromes (CAPS):
Familial Cold Autoinflammatory Syndrome (FCAS),
Muckle-Wells Syndrome (MWS),
MWS with overlapping symptoms of Neonatal Onset Multisystem Inflammatory Disease (NOMID) or Neonatal Onset Multisystem Inflammatory Disease (NOMID),
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: 2008-05-28
Enrollment: 166
Sex: ALL
Minimum age (years): 3
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This will provided long-term safety and efficacy data for ACZ885 (a fully human anti-interleukin-1β \[anti-IL-1β\] monoclonal antibody) given as an injection subcutaneously in patients who participated in the CACZ885A2102 (NCT00487708), CACZ885D2201 (NCT00685373) or CACZ885D2304(NCT00465985) studies or newly identified patients with the following cryopyrin-associated periodic syndromes: Familial Cold Autoinflammatory Syndrome, Muckle-Wells Syndrome or Neonatal Onset Multisystem Inflammatory Disease.

The duration of this study was 6 months with a maximum duration of 2 years


Eligibility criteria: Inclusion Criteria:

1. Male and female patients at least 3 years of age
2. Diagnosis of Familial Cold Autoinflammatory Syndrome, Muckle-Wells Syndrome or Neonatal Onset Multisystem Inflammatory Disease. Prior agreement between the Investigator and Novartis for study eligibility is required for patients who do not have a molecular diagnosis of NALP3 mutations available (either testing not performed, or testing performed but negative)upon study entry. For those patients who have not been molecularly tested for NALP3 mutations, molecular testing should be performed during the course of the study
3. For patients under anakinra therapy or any other investigational IL-1 blocking therapy, these treatments should be discontinued prior to the baseline visit.
4. Patients from the CACZ885A2102 study may enter this study. However, dosing at Visit 2 (Baseline Visit) can only occur if either 1) the patient is experiencing disease flare or 2) at least two months have elapsed from their last injection even in the absence of flare, whichever is earlier.
5. Patients who completed the CACZ885D2304 study may enter this study
6. Patients who completed the CACZ885D2201 study may enter this study
7. Patients who discontinued from the CACZ885A2102, CACZ885D2201 or CACZ885D2304 studies and for whom in the Investigator's judgment (with prior agreement from Novartis) continued treatment with ACZ885 in this study is considered appropriate.

Exclusion Criteria:

1. Participation in any clinical investigation within 4 weeks prior to dosing or longer if required by local regulation with the exception of trials with anakinra, other investigational IL-1 blocking therapies, and/or ACZ885.
2. History of being immunocompromised, including a positive HIV at screening (ELISA and Western blot) test result.
3. A positive Hepatitis B surface antigen (HBsAg) or Hepatitis C antibody test result is not allowed.
4. 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.
5. History of recurrent and/or evidence of active bacterial, fungal, or viral infections.
6. Positive tuberculin skin test reaction (PPD 5 tuberculin units or as according to local standard practice) (\>= 5 mm induration) at 48 to 72 hours after administration at the screening visit or within 2 months prior to the screening visit. Patients who have a positive PPD skin test with a documentation of BCG vaccination, who are at low environmental risk for tuberculosis (TB) infection or reactivation, and have a negative chest X-ray can be included.

Other protocol-defined inclusion/exclusion criteria may apply

Primary outcomes:
measure: The Number of Participants With Adverse Events (AEs), Death, Serious Adverse Events (SAEs), Discontinuation of Study Drug Due to an AE, Infections and Infestations and Injection Site Reactions
timeFrame: 2 years depending on when the participant enters the study
Secondary outcomes:
measure: The Percentage of Participants Without Disease Relapse as Determined by the Physician's Global Assessment of Autoinflammatory Disease Activity, Assessment of Skin Disease and Inflammation Markers.
timeFrame: Every 8 weeks during the course of the trial for at least 6 months with a maximum duration of 2 years
measure: Immunogenicity of Canakinumab (ACZ885)
timeFrame: Every 8 weeks during the course of the trial for at least 6 months with a maximum duration of 2 years
measure: Pharmacokinetics
timeFrame: Every 8 weeks during the course of the trial for at least 6 months with a maximum duration of 2 years
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Little Rock Allergy and Asthma Clinic
state: Arkansas
city: San Francisco
country: United States
facility: UCSF School of Medicine
state: California
city: Columbus
country: United States
facility: Allergy Center at Brookstone
state: Georgia
city: Chicago
country: United States
facility: Rush-Presbyterian St. Lukes Medical Center
state: Illinois
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
city: Laeken
country: Belgium
facility: Novartis Investigative Site
city: Le Kremlin Bicetre
country: France
facility: Novartis Investigative Site
city: Lille Cedex
country: France
facility: Novartis Investigative Site
city: Montpelier Cedex
country: France
facility: Novartis Investigative Site
city: Nantes
country: France
facility: Novartis Investigative site
city: Berlin
country: Germany
facility: Novartis Investigative site
city: Hamburg
country: Germany
facility: Novartis Investigative Site
city: Heidelburg
country: Germany
facility: Novartis Investigative site
city: Herne
country: Germany
facility: Novartis Investigative Site
city: Marburg
country: Germany
facility: Novartis Investigative Site
city: Tubingen
country: Germany
facility: Novartis Investigative site
city: New Delhi
country: India
facility: Novartis Investigative site
city: Genova
country: Italy
facility: Novartis Investigative site
city: Napoli
country: Italy
facility: Novartis Investigative Site
city: Padova
country: Italy
facility: Novartis Investigative Site
city: Rome
country: Italy
facility: Novartis Investigative Site
city: Trieste
country: Italy
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Oviedo
country: Spain
facility: Novartis Investigative site
city: Vigo
country: Spain
facility: Novartis Investigative Site
city: Istanbul
country: Turkey
facility: Novartis Investigative site
city: London
country: United Kingdom
facility: Novartis Investigative site
Study officials:
References:
citation: Kuemmerle-Deschner JB, Hachulla E, Cartwright R, Hawkins PN, Tran TA, Bader-Meunier B, Hoyer J, Gattorno M, Gul A, Smith J, Leslie KS, Jimenez S, Morell-Dubois S, Davis N, Patel N, Widmer A, Preiss R, Lachmann HJ. Two-year results from an open-label, multicentre, phase III study evaluating the safety and efficacy of canakinumab in patients with cryopyrin-associated periodic syndrome across different severity phenotypes. Ann Rheum Dis. 2011 Dec;70(12):2095-102. doi: 10.1136/ard.2011.152728. Epub 2011 Aug 21.