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
  Purpose

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.


Condition Intervention Phase
Systemic Juvenile Idiopathic Arthritis
Drug: Canakinumab
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • 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)


Secondary Outcome Measures:
  • 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.


Enrollment: 84
Study Start Date: July 2009
Study Completion Date: January 2011
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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
Placebo Comparator: Placebo
Patients received a single dose matching placebo of canakinumab on day 1.
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.

  Eligibility

Ages Eligible for Study:   2 Years to 19 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00886769

  Hide Study Locations
Locations
United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35233
United States, Arkansas
Arkansas Children's Hospital Research Inst
Little Rock, Arkansas, United States, 72202
United States, California
Children's Hospital Los Angeles
Los Angeles, California, United States, 90027
United States, District of Columbia
Children's National Medical Center
Washington, District of Columbia, United States, 20010
United States, Illinois
University of Chicago Medical Center
Chicago, Illinois, United States, 60637
United States, Kentucky
University of Louisville
Louisville, Kentucky, United States, 40202
United States, Massachusetts
Tufts New England Medical Center-Dept. of Allergy
Boston, Massachusetts, United States, 02111
Tufts Medical Center
Boston, Massachusetts, United States, 02111
United States, New Jersey
St. Barnabas Ambulatory Care Center
Livingston, New Jersey, United States, 07039
United States, Ohio
Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229
Children's Hospital/Neurology
Cinncinati, Ohio, United States, 45229
Nationwide Children's Hospital
Columbus, Ohio, United States, 43205
United States, Oregon
Legacy Emanuel Hospital
Portland, Oregon, United States, 97227
Legacy Emanual Research
Portland, Oregon, United States, 97232
United States, Texas
Specially For Children
Austin, Texas, United States, 78723
Argentina
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Buenos Aires, Argentina
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Capital Federal, Argentina
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La Plata, Argentina
Belgium
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Bruxelles, Belgium
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Gent, Belgium
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Laeken, Belgium
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Leuven, Belgium
Brazil
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Porto Alegre, Brazil
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Canada, British Columbia
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Vancouver, British Columbia, Canada
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Halifax, Nova Scotia, Canada
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Toronto, Ontario, Canada
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Montreal, Quebec, Canada
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Calgary, Canada
Denmark
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Arhus N, Denmark
France
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Lyon, France
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Paris, France
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Germany
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Bad Bamstedt, Germany
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Berlin, Germany
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Freiburg, Germany
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Garmisch-Partenkirch, Germany
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Geissen, Germany
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Hannover, Germany
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Krefeld, Germany
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Mainz, Germany
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Muenster, Germany
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Saint Augustin, Germany
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Stuttgart, Germany
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Tubingen, Germany
Greece
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Thessaloniki, Greece
Hungary
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Budapest, Hungary
Israel
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Haifa, Israel
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Kfar Saba, Israel
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Petach-Tikva, Israel
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Ramat Gan, Israel
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Rehovot, Israel
Italy
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Bologna, Italy
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Firenze, Italy
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Genova, Italy
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Milano, Italy
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Napoli, Italy
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Padova, Italy
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Rome, Italy
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Scafati, Italy
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Torino, Italy
Netherlands
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Utrecht, Netherlands
Norway
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Oslo, Norway
Peru
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Lima, Peru
Poland
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Warszawa, Poland
South Africa
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Berea, Durban, South Africa
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Mayville, Durban, South Africa
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Pretoria, South Africa
Spain
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Barcelona, Spain
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Madrid, Spain
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Valencia, Spain
Sweden
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Stockholm, Sweden
Switzerland
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Bern, Switzerland
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Lausanne, Switzerland
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Zurich, Switzerland
Turkey
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Ankara, Turkey
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Istanbul, Turkey
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Izmir, Turkey
United Kingdom
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Birmingham, United Kingdom
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Liverpool, United Kingdom
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London, United Kingdom
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Manchester, United Kingdom
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New Castle Upon Tyne, United Kingdom
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Norwich, United Kingdom
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Oxford, United Kingdom
Sponsors and Collaborators
Novartis Pharmaceuticals
International Maternal Pediatric Adolescent AIDS Clinical Trials Group
Southwest Pediatric Nephrology Study Group
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Additional Information:
No publications provided by Novartis

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00886769     History of Changes
Other Study ID Numbers: CACZ885G2305, EudraCT: 2008-005476-27
Study First Received: April 22, 2009
Results First Received: November 21, 2011
Last Updated: March 13, 2012
Health Authority: United States: Food and Drug Administration
Argentina: Ministry of Health
Brazil: Ministry of Health
Belgium: Federal Agency for Medicinal Products and Health Products
Canada: Health Canada
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Paul-Ehrlich-Institut
Hungary: National Institute of Pharmacy
Israel: Ministry of Health
Italy: Ministry of Health
Norway: Norwegian Medicines Agency
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Peru: Ministry of Health
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
South Africa: Medicines Control Council
Spain: Spanish Agency of Medicines
Sweden: Medical Products Agency
Switzerland: Swissmedic
Turkey: Ministry of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Denmark: Ethics Committee

Keywords provided by Novartis:
Flare
arthritis
IL-1beta antagonist
systemic juvenile idiopathic arthritis
Juvenile Rheumatoid
Systemic juvenile idiopathic arthritis with active flare

Additional relevant MeSH terms:
Arthritis
Arthritis, Juvenile
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 27, 2014