Single-dose Study to Assess Efficacy of Canakinumab (ACZ885) in Patients With Active Juvenile Idiopathic Arthritis (SJIA) (β-SPECIFIC 1)

This study has been terminated.
(recommendation by Data Monitoring Committee)
Sponsor:
Collaborators:
International Maternal Pediatric Adolescent AIDS Clinical Trials Group
Southwest Pediatric Nephrology Study Group
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00886769
First received: April 22, 2009
Last updated: March 13, 2012
Last verified: March 2012

April 22, 2009
March 13, 2012
July 2009
December 2010   (final data collection date for primary outcome measure)
Percentage of Patients Who Meet the Adapted American College of Rheumatology (ACR) Pediatric 30 Criteria [ Time Frame: Baseline, Day 15, Day 29 ] [ Designated as safety issue: No ]
Adapted ACR Pediatric 30 criteria determined responders (improved from baseline of at least 30% in at least 3 response variables 1-6 and no intermittent fever in preceding week [variable 7], with no more than one variable 1-6 worsening > 30% ) 1. Physician's Global Assessment of disease activity: 0-100 mm VAS 2.Parent/Patient's Global Assessment of Patient's overall wellbeing: 0-100mmVAS in Child Health Assessment Questionnaire (CHAQ) 3. Functional ability: CHAQ 4.Number of joints with active arthritis 5. Number of joints with limited of motion 6. Laboratory measure of inflammation CRP (mg/L)
Proportion of patients who meet the adapted ACR pediatric 30 criteria [ Time Frame: Day 15 ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00886769 on ClinicalTrials.gov Archive Site
  • Percentage of Patients Achieving the Adapted ACR Pediatric 50 Criteria [ Time Frame: Baseline, Day 15, Day 29 ] [ Designated as safety issue: No ]
    Adapted ACR Pediatric 50 criteria determined responders (improved from baseline of at least 50% in at least 3 response variables 1-6 and no intermittent fever in preceding week [variable 7], with no more than one variable 1-6 worsening > 30%) 1. Physician's Global Assessment of disease activity: 0-100 mm VAS 2. Parent/Patient's Global Assessment of Patient's overall wellbeing: 0-100mmVAS in Child Health Assessment Questionnaire (CHAQ) 3. Functional ability: CHAQ 4. Number of joints with active arthritis 5. Number of joints with limited of motion 6. Laboratory measure of inflammation CRP (mg/L)
  • Percentage of Patients Achieving the Adapted ACR Pediatric 70 [ Time Frame: Baseline, Day 15, Day 29 ] [ Designated as safety issue: No ]
    Adapted ACR Pediatric 70 criteria determined responders (improved from baseline of at least 70% in at least 3 response variables 1-6 and no intermittent fever in preceding week [variable 7], with no more than one variable 1-6 worsening > 30% ) 1. Physician's Global Assessment of disease activity: 0-100 mm VAS 2. Parent/Patient's Global Assessment of Patient's overall wellbeing: 0-100mmVAS in Child Health Assessment Questionnaire (CHAQ) 3. Functional ability: CHAQ 4. Number of joints with active arthritis 5. Number of joints with limited of motion 6. Laboratory measure of inflammation CRP(mg/L)
  • Percentage of Patients Achieving the Adapted ACR Pediatric 90 [ Time Frame: Baseline, Day 15, Day 29 ] [ Designated as safety issue: No ]
    Adapted ACR Pediatric 90 criteria determined responders (improved from baseline of at least 90% in at least 3 response variables 1-6 and no intermittent fever in preceding week [variable 7], with no more than one variable 1-6 worsening > 30% ) 1. Physician's Global Assessment of disease activity: 0-100 mm VAS 2. Parent/Patient's Global Assessment of Patient's overall wellbeing: 0-100mmVAS in Child Health Assessment Questionnaire (CHAQ) 3. Functional ability: CHAQ 4. Number of joints with active arthritis 5. Number of joints with limited of motion 6. Laboratory measure of inflammation CRP(mg/L)
  • Percentage of Patients Achieving the Adapted ACR Pediatric 100 [ Time Frame: baseline, Day 15, Day 29 ] [ Designated as safety issue: No ]
    Adapted ACR Pediatric 100 criteria determined responders (ie improved from baseline of at least 100% in at least 3 response variables 1-6 and no intermittent fever in preceding week [variable 7], with no more than one variable 1-6 worsening > 30% ) 1. Physician's Global Assessment of disease activity: 0-100 mm VAS 2. Parent/Patient's Global Assessment of Patient's overall wellbeing: 0-100mmVAS in Child Health Assessment Questionnaire (CHAQ) 3. Functional ability: CHAQ 4. Number of joints with active arthritis 5. Number of joints with limited of motion 6. Laboratory measure of inflammation
  • 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) [ Time Frame: Baseline, Day 15 ] [ Designated as safety issue: No ]
    CHAQ assessed physical ability and functional status of patients as well as quality of life. The disability dimension consisted of 20 multiple choice items about difficulty in doing eight common activities of daily living; dressing and grooming, arising, eating, walking, reaching, personal hygiene, gripping and activities. Four response categories range from 'without any difficulty' (0) to 'unable to do' (3). The parent's or patient's pain assessment was on VAS that was part of CHAQ. The VAS scale ranges from no pain (0 mm) to very severe pain (100 mm). Negative change indicates improvement.
  • Change in Patient's Pain Intensity as Assessed on a 100-mm Visual Analog Scale (VAS) as Part of CHAQ [ Time Frame: Baseline, Day 29 ] [ Designated as safety issue: No ]
    CHAQ, assessed physical ability and functional status of patients as well as quality of life. The disability dimension consisted of 20 multiple choice items about difficulty in doing eight common activities of daily living; dressing and grooming, arising, eating, walking, reaching, personal hygiene, gripping and activities. Four response categories range from 'without any difficulty'(0) to 'unable to do' (3). The parent's or patient's pain assessment was on VAS that was part of CHAQ. The VAS scale ranges from no pain (0 mm) to very severe pain (100 mm). Negative change indicates improvement.
  • Percentage of Patients Who Had Body Temperature ≤ 38°C [ Time Frame: Day 3 ] [ Designated as safety issue: No ]
    Body temperature was derived from vital signs evaluation. No conversion of body temperature was performed, no matter how it was measured.
  • Change in Health-related Quality of Life (HRQoL)Over Time by Use of the Child Health Questionnaire - Parent Form (CHQ-PF50) [ Time Frame: Over 4 week study period (Baseline, Day 15, Day 29) ] [ Designated as safety issue: No ]
    CHQ-PF50 measures HRQoL in children 5-18 years old from parent's perspective. Questionnaire completed by parent without input from patient. Total score ranges from 0-100. Increases in scores represent improved well-being in subjects as assessed by their parents. Mixed linear model on change from baseline in CHQ-PF50 score with treatment group, stratification factors, day of assessment and interaction between group and day as covariates. Covariance analysis used a repeated measures approach, so all timepoints over time were taken into account.
  • Change in Disability Score Over Time by Use of the CHAQ [ Time Frame: At 4 week study period ] [ Designated as safety issue: No ]
    The disability dimension of CHAQ consisted of 20 multiple choice items about difficulty in doing eight common activities of daily living; dressing and grooming, arising, eating, walking, reaching, personal hygiene, gripping and activities. Four response categories range from 'without any difficulty'(0) to 'unable to do' (3). Mixed linear model on change from baseline in CHAQ score included treatment group, stratification factors, day of assessment and interaction between group and day as covariates. Negative change indicates improvement.
  • Proportion of patients achieving the adapted ACR Pediatric 30 criteria [ Time Frame: Day 29 ] [ Designated as safety issue: No ]
  • Proportion of patients achieving the adapted ACR Pediatric 50/70/90/100 criteria [ Time Frame: the 4 week study period ] [ Designated as safety issue: No ]
  • Change in patient's pain intensity as assessed on a 100-mm visual analog scale [ Time Frame: During the 4 week study period ] [ Designated as safety issue: No ]
  • Proportion of patients who show clinical signs of response [ Time Frame: Day 3 ] [ Designated as safety issue: No ]
  • Change in health-related quality of life over time by use of the CHQ [ Time Frame: During the 4 week study period ] [ Designated as safety issue: No ]
  • Change in disability over time by use of the CHAQ [ Time Frame: During the 4 week study period ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Single-dose Study to Assess Efficacy of Canakinumab (ACZ885) in Patients With Active Juvenile Idiopathic Arthritis (SJIA)
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

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.

Not Provided
Interventional
Phase 3
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Systemic Juvenile Idiopathic Arthritis
  • Drug: Canakinumab
    Canakinumab was supplied in individual 6 mL glass vials each containing 150 mg canakinumab powder as a lyophilized cake. Each reconstituted vial provided 150mg of canakinumab per 1 mL.
    Other Name: ACZ885
  • Drug: Placebo
    Placebo was provided in individual 6 mL glass vials each containing 150 mg placebo powder matching canakinumab as a lyophilized cake. Each reconstitued vial provided 150mg of placebo per 1 mL.
  • Experimental: Canakinumab
    Patients received a single dose of subcutaneous(sc) injection of canakinumab (4 mg/kg) on Day 1. Maximal total single dose of canakinumab allowed was 300 mg. Any patient who required a dose greater than 150 mg (patients>37.5 kg) received two sc injections.
    Intervention: Drug: Canakinumab
  • Placebo Comparator: Placebo
    Patients received a single dose matching placebo of canakinumab on day 1.
    Intervention: Drug: Placebo
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
84
January 2011
December 2010   (final data collection date for primary outcome measure)

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
Both
2 Years to 19 Years
No
Contact information is only displayed when the study is recruiting subjects
United States,   Argentina,   Belgium,   Brazil,   Canada,   Denmark,   France,   Germany,   Greece,   Hungary,   Israel,   Italy,   Netherlands,   Norway,   Peru,   Poland,   South Africa,   Spain,   Sweden,   Switzerland,   Turkey,   United Kingdom
 
NCT00886769
CACZ885G2305, EudraCT: 2008-005476-27
Not Provided
Novartis ( Novartis Pharmaceuticals )
Novartis Pharmaceuticals
  • International Maternal Pediatric Adolescent AIDS Clinical Trials Group
  • Southwest Pediatric Nephrology Study Group
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Novartis
March 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP