Clinical trial NCT00889863: Flare Prevention Study of Canakinumab in Patients With Active Systemic Juvenile Idiopathic Arthritis (SJIA)
Official title: A Randomized, Double-blind, Placebo Controlled, Withdrawal Study of Flare Prevention of Canakinumab (ACZ885) in Patients With Systemic Juvenile Idiopathic Arthritis (SJIA) and Active Systemic Manifestations
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Systemic Juvenile Idiopathic Arthritis With Active Flare
Keywords: Flare
arthritis
IL-1beta antagonist
systemic juvenile idiopathic arthritis
Juvenile rheumatoid
Lead sponsor: Novartis
Sponsor class: INDUSTRY
Collaborators: name: Pediatric Rheumatology International Trials Organization
First posted: 2009-04-29
Enrollment: 177
Sex: ALL
Minimum age (years): 2
Maximum age (years): 19
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This two-part study assessed the sustained efficacy of canakinumab in the double-blind Part II and the ability to taper steroids in the open label Part I.


Eligibility criteria: Inclusion Criteria:

* Confirmed diagnosis of systemic juvenile idiopathic arthritis as per International League Against Rheumatism (ILAR) definition that must have occurred at least 2 months prior to enrollment with onset of disease \< 16 years of age.

  -Arthritis in one or more joints with or preceded by fever of at least 2 weeks duration that is documented to be daily for at least 3 days with accompanying symptoms
* Active disease at the time of enrollment defined as follows:

  * At least 2 joints with active arthritis (using American College of rheumatology) ACR definition of active joint)
  * Documented spiking, intermittent fever (body temperature \> 38oC) for at least 1 day during the screening period within 1 week before first study drug dose
  * C-reactive protein \> 30 mg/L (normal range \< 10 mg/L)
* No concomitant use of second line agents such as disease-modifying and/ or immunosuppressive drugs will be allowed with the exception of:

  * Stable dose of methotrexate for at least 8 weeks prior to the screening visit, and/or folic/folinic acid per standard medical practice
  * Stable dose of no more than one non-steroidal anti-inflammatory drug for at least 2 weeks prior to the screening visit
  * Stable dose of steroid treatment \< or = to 1.0 mg/kg/day in 1-2 doses per day of oral prednisone or equivalent

Exclusion criteria:

* Diagnosis of active macrophage-activation syndrome (MAS) within the last 6 months
* Risk factors for tuberculosis
* Patients with active or recurrent bacterial, fungal or viral infection at the time of enrollment, including patients with evidence of HIV infection, Hepatitis B and Hepatitis C infection

Other protocol inclusion/exclusion criteria may apply

Primary outcomes:
measure: Part I: Percentage of Patients Who Were on Steroids at Entry Into Part I and Who Were Able to Taper Steroid as Per Protocol in at Least 25% of the Patients Who Entered the Study Taking a Steroid
timeFrame: 32 Weeks
measure: Part II: Survival Estimate of Time to Flare
timeFrame: Part II was event driven. The study was stopped when the required number of 37 flares had occurred (88 weeks)
Secondary outcomes:
measure: Part I: Percentage of Patients on Steroids at Study Start Who Reached a Steroid Dose ≤0.2 mg/kg at End of Part Ic
timeFrame: 28 Weeks
measure: Part I: Percentage of Participants on Steroids at the Start of 1c Who Were Able to Taper Steroids by the End of Part 1c
timeFrame: Start of Part Ic (After Week 8) to End of Part Ic (Week 28)
measure: Part I: Percentage of Participants With Minimum American College of Rheumatology (ACR) 30/50/70/90/100 at the End of Part I
timeFrame: Baseline, 32 Weeks
measure: Part I: Time to First Minimum American College of Rheumatology (ACR50) and Normal C-Reactive Protein
timeFrame: Baseline, Week 32
measure: Part I: Time to First Minimum American College of Rheumatology (ACR70) and Normal C-Reactive Protein
timeFrame: Baseline, Week 32
measure: Part I: Percentage of Participants With Body Temperature ≤ 38 Degrees Celsius at Day 3 in Part 1a
timeFrame: Day 3
measure: Part II: Survival Analysis of Time to a Worsening in American College of Rheumatology (ACR) Response
timeFrame: Part II was event driven. The study was stopped when the required number of 37 flares had occurred (88 weeks)
measure: Part I: Change in Disability Over Time in the Child Health Assessment Questionnaire-Disability Index (CHAQ-DI) From Baseline to End of Part I
timeFrame: Baseline, End of Part I (Week 32)
measure: Part II: Change in Disability Over Time by the Child Health Assessment Questionnaire-Disability Index (CHAQ-DI)
timeFrame: Start of Part II (Week 32), End of Part II ( total duration-88 weeks)
measure: Part I: Change in Health Related Quality of Life Over Time by Child Health Questionnaire (CHQ-PF50)
timeFrame: Baseline, End of Part I ( Week 32)
measure: Part II: Change in Health Related Quality of Life Over Time by Child Health Questionnaire (CHQ-PF50)
timeFrame: Start Part II (Week 32), End Part II (total duration - 88 Weeks)
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Arkansas Children's Hospital Research Inst
state: Arkansas
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Louisville
country: United States
facility: University of Louisville
state: Kentucky
city: Boston
country: United States
facility: New England Medical Center - Department of Allergy
state: Massachusetts
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Livingston
country: United States
facility: St Barnabas Ambulatory Care Center
state: New Jersey
city: Cincinnati
country: United States
facility: Children's Hospital Medical Center
state: Ohio
city: Cincinnati
country: United States
facility: Children's Hospital/Neurology
state: Ohio
city: Portland
country: United States
facility: Legacy Emanuel Hospital
state: Oregon
city: Portland
country: United States
facility: Legacy Emanual Research
state: Oregon
city: Austin
country: United States
facility: Specially For Children
state: Texas
city: Buenos Aires
country: Argentina
facility: Novartis Investigative Site
city: Capital Federal
country: Argentina
facility: Novartis Investigative Site
city: La Plata
country: Argentina
facility: Novartis Investigative Site
city: Bruxelles
country: Belgium
facility: Novartis Investigative site
city: Gent
country: Belgium
facility: Novartis Investigative site
city: Laeken
country: Belgium
facility: Novartis Investigative Site
city: Leuven
country: Belgium
facility: Novartis Investigative site
city: Curitiba
country: Brazil
facility: Novartis Investigative Site
city: Porto Alegre
country: Brazil
facility: Novartis Investigative site
city: Rio de Janiero
country: Brazil
facility: Novartis Investigative site
city: Sao Paulo
country: Brazil
facility: Novartis Investigative site
city: Vancouver
country: Canada
facility: Novartis Investigative site
state: British Columbia
city: Halifax
country: Canada
facility: Novartis Investigative site
state: Nova Scotia
city: Toronto
country: Canada
facility: Novartis Investigative site
state: Ontario
city: Montreal
country: Canada
facility: Novartis Investigative site
state: Quebec
city: Le Kremlin Bicetre
country: France
facility: Novartis Investigative Site
city: Lyon
country: France
facility: Novartis Investigative Site
city: Paris
country: France
facility: Novartis Investigative Site
city: Strasbourg
country: France
facility: Novartis Investigative Site
city: Bad Bamstedt
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative site
city: Bremen
country: Germany
facility: Novartis Investigative Site
city: Freiburg
country: Germany
facility: Novartis Investigative Site
city: Geissen
country: Germany
facility: Novartis Investigative Site
city: Hamburg
country: Germany
facility: Novartis Investigative Site
city: Muenster
country: Germany
facility: Novartis Investigative Site
city: Saint Augustin
country: Germany
facility: Novartis Investigative Site
city: Stuttgart
country: Germany
facility: Novartis Investigative Site
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Haifa
country: Israel
facility: Novartis Investigative Site
city: Kfar Saba
country: Israel
facility: Novartis Investigative Site
city: Petach-Tikva
country: Israel
facility: Novartis Investigative Site
city: Ramat Gan
country: Israel
facility: Novartis Investigative Site
city: Rehovot
country: Israel
facility: Novartis Investigative Site
city: Bologna
country: Italy
facility: Novartis Investigative Site
city: Firenze
country: Italy
facility: Novartis Investigative Site
city: Genova
country: Italy
facility: Novartis Investigative Site
city: Milano
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: Scafati
country: Italy
facility: Novartis Investigative site
city: Torino
country: Italy
facility: Novartis Investigative site
city: Utrecht
country: Netherlands
facility: Novartis Investigative site
city: Oslo
country: Norway
facility: Novartis Investigative Site
city: Lima
country: Peru
facility: Novartis Investigative Site
city: Warszawa
country: Poland
facility: Novartis Investigative site
city: Berea
country: South Africa
facility: Novartis Investigative site
state: Durban
city: Mayville
country: South Africa
facility: Novartis Investigative site
state: Durban
city: Johannesburg
country: South Africa
facility: Novartis Investigative site
city: Pretoria
country: South Africa
facility: Novartis Investigative site
city: Barcelona
country: Spain
facility: Novartis Investigative site
city: Madrid
country: Spain
facility: Novartis Investigative site
city: Valencia
country: Spain
facility: Novartis Investigative site
city: Stockholm
country: Sweden
facility: Novartis Investigative site
city: Bern
country: Switzerland
facility: Novartis Investigative Site
city: Lausanne
country: Switzerland
facility: Novartis Investigative site
city: Zurich
country: Switzerland
facility: Novartis Investigative site
city: Ankara
country: Turkey
facility: Novartis Investigative site
city: Istanbul
country: Turkey
facility: Novartis Investigative Site
city: Izmir
country: Turkey
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Ruperto N, Brunner HI, Quartier P, Constantin T, Wulffraat NM, Horneff G, Kasapcopur O, Schneider R, Anton J, Barash J, Berner R, Corona F, Cuttica R, Fouillet-Desjonqueres M, Fischbach M, Foster HE, Foell D, Radominski SC, Ramanan AV, Trauzeddel R, Unsal E, Levy J, Vritzali E, Martini A, Lovell DJ; Paediatric Rheumatology International Trials Organisation (PRINTO) and the Pediatric Rheumatology Collaborative Study Group (PRCSG). Canakinumab in patients with systemic juvenile idiopathic arthritis and active systemic features: results from the 5-year long-term extension of the phase III pivotal trials. Ann Rheum Dis. 2018 Dec;77(12):1710-1719. doi: 10.1136/annrheumdis-2018-213150. Epub 2018 Sep 29.
citation: Brachat AH, Grom AA, Wulffraat N, Brunner HI, Quartier P, Brik R, McCann L, Ozdogan H, Rutkowska-Sak L, Schneider R, Gerloni V, Harel L, Terreri M, Houghton K, Joos R, Kingsbury D, Lopez-Benitez JM, Bek S, Schumacher M, Valentin MA, Gram H, Abrams K, Martini A, Lovell DJ, Nirmala NR, Ruperto N; Pediatric Rheumatology International Trials Organization (PRINTO) and the Pediatric Rheumatology Collaborative Study Group (PRCSG). Early changes in gene expression and inflammatory proteins in systemic juvenile idiopathic arthritis patients on canakinumab therapy. Arthritis Res Ther. 2017 Jan 23;19(1):13. doi: 10.1186/s13075-016-1212-x.
citation: Grom AA, Ilowite NT, Pascual V, Brunner HI, Martini A, Lovell D, Ruperto N; Paediatric Rheumatology International Trials Organisation and the Pediatric Rheumatology Collaborative Study Group; Leon K, Lheritier K, Abrams K. Rate and Clinical Presentation of Macrophage Activation Syndrome in Patients With Systemic Juvenile Idiopathic Arthritis Treated With Canakinumab. Arthritis Rheumatol. 2016 Jan;68(1):218-28. doi: 10.1002/art.39407.
citation: Ruperto N, Brunner HI, Quartier P, Constantin T, Wulffraat N, Horneff G, Brik R, McCann L, Kasapcopur O, Rutkowska-Sak L, Schneider R, Berkun Y, Calvo I, Erguven M, Goffin L, Hofer M, Kallinich T, Oliveira SK, Uziel Y, Viola S, Nistala K, Wouters C, Cimaz R, Ferrandiz MA, Flato B, Gamir ML, Kone-Paut I, Grom A, Magnusson B, Ozen S, Sztajnbok F, Lheritier K, Abrams K, Kim D, Martini A, Lovell DJ; PRINTO; PRCSG. Two randomized trials of canakinumab in systemic juvenile idiopathic arthritis. N Engl J Med. 2012 Dec 20;367(25):2396-406. doi: 10.1056/NEJMoa1205099.