Clinical trial NCT00886769: Single-dose Study to Assess Efficacy of Canakinumab (ACZ885) in Patients With Active Juvenile Idiopathic Arthritis (SJIA)
Official title: A Randomized, Double-blind, Placebo Controlled, Single-dose Study to Assess the Initial Efficacy of Canakinumab (ACZ885) With Respect to the Adapted ACR Pediatric 30 Criteria in Patients With Systemic Juvenile Idiopathic Arthritis (SJIA) and Active Systemic Manifestations
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Systemic Juvenile Idiopathic Arthritis
Keywords: Flare
arthritis
IL-1beta antagonist
systemic juvenile idiopathic arthritis
Juvenile Rheumatoid
Systemic juvenile idiopathic arthritis with active flare
Lead sponsor: Novartis
Sponsor class: INDUSTRY
Collaborators: name: International Maternal Pediatric Adolescent AIDS Clinical Trials Group
name: Southwest Pediatric Nephrology Study Group
First posted: 2009-04-23
Enrollment: 84
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 study assessed the initial efficacy and safety of canakinumab over a 4 week period in patients with systemic juvenile idiopathic arthritis (SJIA) having a flare. Response to treatment will be according to the adapted American College of Rheumatology(ACR)Pediatric 30 criteria at Day 15.


Eligibility criteria: Inclusion Criteria:

1. Confirmed diagnosis of systemic juvenile idiopathic arthritis as per 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/quotidian for at least 3 days and accompanied by one or more of the following:
   * evanescent nonfixed erythematous rash,
   * generalized lymph node enlargement,
   * hepatomegaly and/ or splenomegaly,
   * serositis
2. Parent's or legal guardian's written informed consent and child's assent, if appropriate, or patient's informed consent for ≥ 18 years of age
3. Male and female patients aged ≥ 2 to \< 20 years of age
4. Active disease at the time of enrollment defined as follows:

   * At least 2 joints with active arthritis
   * Documented spiking, intermittent fever (body temperature \> 38°C) for at least 1 day during the screening period within 1 week before first canakinumab/placebo dose
   * C-reactive protein (CRP) \> 30 mg/L (normal range \< 10 mg/L)
5. Naïve to canakinumab
6. Other protocol defined inclusion criteria may apply

Exclusion Criteria:

Patients who fulfilled one or more of the following criteria were not eligible for inclusion in this study:

1. Pregnant or nursing (lactating) female patients
2. Female patients having reached sexual maturity unless their career, lifestyle, or sexual orientation precluded intercourse with a male partner and/or they were using an acceptable method of contraception
3. History of hypersensitivity to study drug or to biologics.
4. Diagnosis of active macrophage-activation syndrome (MAS) (Ravelli, Magni-Manzoni and Pistorio 2005) within the last 6 months
5. With active or recurrent bacterial, fungal or viral infection, including patients with evidence of human immunodeficiency virus (HIV) infection, hepatitis B or hepatitis C infection
6. Other protocol defined exclusion criteria may apply

Primary outcomes:
measure: Percentage of Patients Who Meet the Adapted American College of Rheumatology (ACR) Pediatric 30 Criteria
timeFrame: Baseline, Day 15, Day 29
Secondary outcomes:
measure: Percentage of Patients Achieving the Adapted ACR Pediatric 50 Criteria
timeFrame: Baseline, Day 15, Day 29
measure: Percentage of Patients Achieving the Adapted ACR Pediatric 70
timeFrame: Baseline, Day 15, Day 29
measure: Percentage of Patients Achieving the Adapted ACR Pediatric 90
timeFrame: Baseline, Day 15, Day 29
measure: Percentage of Patients Achieving the Adapted ACR Pediatric 100
timeFrame: baseline, Day 15, Day 29
measure: Change in Patient's Pain Intensity as Assessed on a 100-mm Visual Analog Scale (VAS)as Part of the Childhood Health Assessment Questionnaire(CHAQ)
timeFrame: Baseline, Day 15
measure: Change in Patient's Pain Intensity as Assessed on a 100-mm Visual Analog Scale (VAS) as Part of CHAQ
timeFrame: Baseline, Day 29
measure: Percentage of Patients Who Had Body Temperature ≤ 38°C
timeFrame: Day 3
measure: Change in Health-related Quality of Life (HRQoL)Over Time by Use of the Child Health Questionnaire - Parent Form (CHQ-PF50)
timeFrame: Over 4 week study period (Baseline, Day 15, Day 29)
measure: Change in Disability Score Over Time by Use of the CHAQ
timeFrame: At 4 week study period
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Little Rock
country: United States
facility: Arkansas Children's Hospital Research Inst
state: Arkansas
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
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: Tufts Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Tufts New England Medical Center-Dept. of Allergy
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: Cinncinati
country: United States
facility: Children's Hospital/Neurology
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital
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 Janeiro
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: Calgary
country: Canada
facility: Novartis Investigative site
city: Arhus N
country: Denmark
facility: Novartis Investigative site
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: Strassbourg
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: Dresden
country: Germany
facility: Novartis Investigative site
city: Freiburg
country: Germany
facility: Novartis Investigative Site
city: Garmisch-Partenkirch
country: Germany
facility: Novartis Investigative site
city: Geissen
country: Germany
facility: Novartis Investigative Site
city: Hamburg
country: Germany
facility: Novartis Investigative Site
city: Hannover
country: Germany
facility: Novartis Investigative site
city: Krefeld
country: Germany
facility: Novartis Investigative site
city: Mainz
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: Tubingen
country: Germany
facility: Novartis Investigative site
city: Thessaloniki
country: Greece
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: 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
city: Birmingham
country: United Kingdom
facility: Novartis Investigative site
city: Liverpool
country: United Kingdom
facility: Novartis Investigative site
city: London
country: United Kingdom
facility: Novartis Investigative site
city: Manchester
country: United Kingdom
facility: Novartis Investigative site
city: New Castle Upon Tyne
country: United Kingdom
facility: Novartis Investigative site
city: Norwich
country: United Kingdom
facility: Novartis Investigative site
city: Oxford
country: United Kingdom
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.