Clinical trial NCT00891046: An Open-label Extension Study of Canakinumab in Patients With Systemic Juvenile Idiopathic Arthritis and Active Systemic Manifestations Manifestations and Response Characterization Study in Canakinumab Treatment-naïve Patients With Active SJIA With and Without Fever.
Official title: An Open-label Extension Study of Canakinumab (ACZ885) in Patients With Systemic Juvenile Idiopathic Arthritis (SJIA) and Active Systemic Manifestations Who Participated in Studies ACZ885G2301 and ACZ885G2305; and Response Characterization Study in Canakinumab Treatment-naïve Patients With Active SJIA With and Without Fever
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Systemic Juvenile Idiopathic Arthritis
Keywords: Flare
arthritis
IL-1beta antagonist
systemic juvenile idiopathic arthritis
CHAQ
steroids
ACR pediatric response
Systemic juvenile idiopathic arthritis with active flare
Lead sponsor: Novartis
Sponsor class: INDUSTRY
Collaborators: name: Pediatric Rheumatology International Trials Organization
First posted: 2009-04-30
Enrollment: 270
Sex: ALL
Minimum age (years): 2
Maximum age (years): 19
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This open-label extension study will permit patients with Systemic Juvenile Idiopathic Arthritis (SJIA) who previously were responsive to treatment with canakinumab and canakinumab treatment-naïve patients with active SJIA with and without fever to be retreated with 4 mg/kg s.c. every 4 weeks and assessed for continued efficacy and safety until discontinuation or when study CACZ885G2402 is in place at their study center or around March 2013, whichever occurs first. Patients who are steroid-free will be able to taper their canakinumab dose to 2 mg/kg s.c. every 4 weeks.


Eligibility criteria: Inclusion criteria:

* Patients from study CACZ885G2305 or CACZ885G2301 who achieved an adapted ACR pediatric 30 response 15 days after their initial dose of canakinumab but clinically deteriorated afterwards or a minimum ACR Pediatric 30 response was not maintained after Day 15 and intervention is deemed necessary by the investigator, or Patients in study CACZ885G2301 who are not eligible to enter Part II (withdrawal part) because they were not able to meet the corticosteroid entry criteria , or Responder patients in Part I or Part II who had not flared when CACZ885G2301 was stopped, or CACZ885G2301 patients who were responders in Part I but experienced a flare in Part II.
* Treatment-naïve patients need to meet the following criteria:

  * 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
  * Male and female patients aged ≥ 2 to \< 20 years of age
  * Active disease at the time of enrollment defined as having 2 or more of the following:

    * Documented spiking, intermittent fever (body temperature \> 38°C) for at least 1 day during the screening period and within 1 week before first canakinumab dose
    * At least 2 joints with active arthritis
    * AND C-reactive protein (CRP) \> 30 mg/L (normal range \< 10 mg/L) Rash Serositis Lymphadenopathy Hepatosplenomegaly
  * Naïve to canakinumab

Other protocol-defined inclusion criteria may apply

Exclusion criteria:

* History of allergy or hypersensitivity to study drug
* With active or recurrent bacterial, fungal or viral infections at time of enrollment

Other protocol inclusion/exclusion criteria may apply

Primary outcomes:
measure: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), AEs by Severity, AEs Leading to Discontinuation, SAEs Leading to Discontinuation, Treatment Related AEs and SAE
timeFrame: From start of study treatment (Day 1) up to end of follow-up period (Week 271 for ACZ885 treated participants and Week 145 for ACZ885 treatment naive participants)
measure: Number of Participants With Anti -ACZ885 Antibodies at Any Visit During the Study
timeFrame: From start of study treatment (Day 1) up to end of follow-up period (Week 271 for ACZ885 treated participants and Week 145 for ACZ885 treatment naive participants)
measure: Number of Participants With Clinically Significant Local Injection Site Reactions During the Study
timeFrame: From start of study treatment (Day 1) up to end of follow-up period (Week 271 for ACZ885 treated participants and Week 145 for ACZ885 treatment naive participants)
measure: Percentage of Participants Previously Treated With Anakinra Who Achieved Minimum Response of American College of Rheumatology (ACR) Pediatric 30/50/70/90/100 at Last Assessment of Study
timeFrame: Baseline up to last assessment (4 years) or date of discontinuation, which ever occurred earlier
measure: Percentage of Participants Previously Treated With Tocilizumab Who Achieved Minimum Response of American College of Rheumatology (ACR) Pediatric 30/50/70/90/100 at Last Assessment of Study
timeFrame: Baseline up to last assessment (4 years) or date of discontinuation, which ever occurred earlier
measure: Percentage of Participants Previously Treated With Other Biologics Who Achieved Minimum Response of American College of Rheumatology (ACR) Pediatric 30/50/70/90/100 at Last Assessment of Study
timeFrame: Baseline up to last assessment (4 years) or date of discontinuation, which ever occurred earlier
Secondary outcomes:
measure: Percentage of Non--Responders Who Achieved Minimum Response of American College of Rheumatology (ACR) Pediatric 30/50/70/90/100
timeFrame: Baseline up to last assessment (4 years) or date of discontinuation, which ever occurred earlier
measure: Percentage of Participants With Minimum Adapted ACR Pediatric ≥ 30 at Baseline Who Achieved Minimum Response of ACR Pediatric 30/50/70/90/100 at Last Assessment of Study
timeFrame: Baseline up to last assessment (4 years) or date of discontinuation, which ever occurred earlier
measure: Percentage of Participants Able to Taper Oral Steroid Use or Reached Steroid Free Regimen
timeFrame: Baseline up to last assessment (4 years) or date of discontinuation, which ever occurred earlier
measure: Number of Participants Who Reduced Their Canakinumab Dose to 2 mg/kg
timeFrame: Baseline up to last assessment (4 years) or date of discontinuation, which ever occurred earlier
measure: Percentage of Participants With Clinical Remission
timeFrame: Baseline up to last assessment (4 years) or date of discontinuation, which ever occurred earlier
measure: Change From Baseline in Disability, Overall Well-Being and Pain Intensity Scores Based on Child Health Assessment Questionnaire (CHAQ) to Last Assessment of Study
timeFrame: Baseline up to last assessment (4 years) or date of discontinuation, which ever occurred earlier
measure: Change From Baseline in Health-Related Quality of Life (HRQoL) Over Time Based on Child Health Questionnaire- Parent Form (CHQ-PF50) to Last Assessment of Study
timeFrame: Baseline up to last assessment (4 years) or date of discontinuation, which ever occurred earlier
measure: Change From Baseline in EuroQual 5 -Dimension Health Status Questionnaire (EQ-5D) Utility Index and Health State Assessment Scores [EQ Visual Analog Scale (EQ-VAS)] to Last Assessment of Study
timeFrame: Baseline up to last assessment (4 years) or date of discontinuation, which ever occurred earlier
measure: Change From Baseline in Pediatric Daytime Sleepiness Scale (PDSS) Score to Last Assessment of Study
timeFrame: Baseline up to last assessment (4 years) or date of discontinuation, which ever occurred earlier
measure: Change From Baseline in Growth Velocity Parameter for Height to Last Assessment of Study
timeFrame: Baseline up to last assessment (4 years) or date of discontinuation, which ever occurred earlier
measure: Percentage of Participants With Inactive Disease
timeFrame: Baseline up to last assessment (4 years) or date of discontinuation, which ever occurred earlier
measure: Change From Baseline in Growth Velocity Parameters to Last Assessment of Study
timeFrame: Baseline up to last assessment (4 years) or date of discontinuation, which ever occurred earlier
measure: Change From Baseline in Growth Velocity Parameter for BMI to Last Assessment of Study
timeFrame: Baseline up to last assessment (4 years) or date of discontinuation, which ever occurred earlier
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Novartis Investigative Site
state: California
city: Louisville
country: United States
facility: Novartis Investigative Site
state: Kentucky
city: Boston
country: United States
facility: Novartis Investigative Site
state: Massachusetts
city: Cincinnati
country: United States
facility: Novartis Investigative Site
state: Ohio
city: Columbus
country: United States
facility: Novartis Investigative Site
state: Ohio
city: Portland
country: United States
facility: Novartis Investigative Site
state: Oregon
city: Caba
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Vienna
country: Austria
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
state: PR
city: Rio de Janeiro
country: Brazil
facility: Novartis Investigative Site
state: RJ
city: Rio de Janeiro
country: Brazil
facility: Novartis Investigative Site
state: RJ
city: São Paulo
country: Brazil
facility: Novartis Investigative Site
state: SP
city: Vancouver
country: Canada
facility: Novartis Investigative Site
state: British Columbia
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 cedex 15
country: France
facility: Novartis Investigative Site
city: Strasbourg
country: France
facility: Novartis Investigative Site
city: Bad Bramstedt
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Freiburg
country: Germany
facility: Novartis Investigative Site
city: Garmisch-Partenkirchen
country: Germany
facility: Novartis Investigative Site
city: Gießen
country: Germany
facility: Novartis Investigative Site
city: Hamburg
country: Germany
facility: Novartis Investigative Site
city: Hamburg
country: Germany
facility: Novartis Investigative Site
city: Hannover
country: Germany
facility: Novartis Investigative Site
city: Heidelberg
country: Germany
facility: Novartis Investigative Site
city: Muenster
country: Germany
facility: Novartis Investigative Site
city: Saint Augustin
country: Germany
facility: Novartis Investigative Site
city: Tübingen
country: Germany
facility: Novartis Investigative Site
city: Ampelokipi
country: Greece
facility: Novartis Investigative Site
state: GR
city: Thessaloniki
country: Greece
facility: Novartis Investigative Site
state: GR
city: Goudi- Athens
country: Greece
facility: Novartis Investigative Site
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Haifa
country: Israel
facility: Novartis Investigative Site
city: Kfar-Sava
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: Firenze
country: Italy
facility: Novartis Investigative Site
state: FI
city: Genova
country: Italy
facility: Novartis Investigative Site
state: GE
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Napoli
country: Italy
facility: Novartis Investigative Site
city: Utrecht
country: Netherlands
facility: Novartis Investigative Site
city: Breña
country: Peru
facility: Novartis Investigative Site
state: Lima
city: Warszawa
country: Poland
facility: Novartis Investigative Site
city: Moscow
country: Russian Federation
facility: Novartis Investigative Site
city: Moscow
country: Russian Federation
facility: Novartis Investigative Site
city: Saint-Petersburg
country: Russian Federation
facility: Novartis Investigative Site
city: Esplugues de Llobregat
country: Spain
facility: Novartis Investigative Site
state: Barcelona
city: Valencia
country: Spain
facility: Novartis Investigative Site
state: Comunidad Valenciana
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Stockholm
country: Sweden
facility: Novartis Investigative Site
city: Lausanne
country: Switzerland
facility: Novartis Investigative Site
city: Ankara
country: Turkey
facility: Novartis Investigative Site
city: Balcova / Izmir
country: Turkey
facility: Novartis Investigative Site
city: Fatih / Istanbul
country: Turkey
facility: Novartis Investigative Site
city: Istanbul
country: Turkey
facility: Novartis Investigative Site
city: Bath
country: United Kingdom
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: Newcastle Upon Tyme
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: 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.