Flare Prevention Study of Canakinumab in Patients With Active Systemic Juvenile Idiopathic Arthritis (SJIA) (β-SPECIFIC 2)

This study has been completed.
Sponsor:
Collaborator:
Pediatric Rheumatology International Trials Organization
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00889863
First received: April 21, 2009
Last updated: September 13, 2012
Last verified: September 2012
  Purpose

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.


Condition Intervention Phase
Systemic Juvenile Idiopathic Arthritis With Active Flare
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, Withdrawal Study of Flare Prevention of Canakinumab (ACZ885) 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:
  • 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 [ Time Frame: 32 Weeks ] [ Designated as safety issue: No ]
    Ability to taper oral steroids: if dose reduced from start of Part I to end of Part Ic from > 0.8 mg/kg/day to ≤ 0.5 mg/kg/day, or from ≥ 0.5 mg/kg/day and ≤ 0.8 mg/kg/day by at least 0.3 mg/kg, or from any initial dose to ≤ 0.2 mg/kg/day, while maintaining a minimum adapted ACR 30 pediatric criterion. Patients on oral steroids at study entry who did not enter Part 1c are considered steroid tapering failures.

  • Part II: Survival Estimate of Time to Flare [ Time Frame: Part II was event driven. The study was stopped when the required number of 37 flares had occurred (88 weeks) ] [ Designated as safety issue: No ]

    Kaplan Meier estimate of the probability to experience a flare. Flare was defined as at least 1 of the following.

    • Reappearance of fever (>38°C, lasting for at least 2 consecutive days) not due to infections
    • Flare according to the JIA pediatric criteria for flare (all criteria must have been met):
    • ≥ 30% worsening in at least 3 of the first 6 response variables
    • ≥ 30% improvement in not more than 1 of the first 6 response variables Patients who discontinued the study while in Part II were counted as flared unless they discontinued because of inactive disease for at least 24 weeks in Part II.


Secondary Outcome Measures:
  • Part I: Percentage of Patients on Steroids at Study Start Who Reached a Steroid Dose ≤0.2 mg/kg at End of Part Ic [ Time Frame: 28 Weeks ] [ Designated as safety issue: No ]
  • Part I: Percentage of Participants on Steroids at the Start of 1c Who Were Able to Taper Steroids by the End of Part 1c [ Time Frame: Start of Part Ic (After Week 8) to End of Part Ic (Week 28) ] [ Designated as safety issue: No ]
  • Part I: Percentage of Participants With Minimum American College of Rheumatology (ACR) 30/50/70/90/100 at the End of Part I [ Time Frame: Baseline, 32 Weeks ] [ Designated as safety issue: No ]

    Adapted ACR Pediatric 30/50/70/90/100 criteria are defined as meeting all of the following:

    • improvement from baseline of ≥ 30%, ≥ 50%, ≥ 70%, ≥ 90%, or 100%, in at least 3 of the first 6 response variables

      1. Physician's global assessment of disease activity
      2. CHAQ-patient's overall well-being
      3. CHAQ-Functional ability
      4. # of joints with active arthritis
      5. # of joints with limitation of motion
      6. C-Reactive Protein.
    • no intermittent fever in the preceding week
    • no more than one of the first 6 response variables worsening by more than 30%

  • Part I: Time to First Minimum American College of Rheumatology (ACR50) and Normal C-Reactive Protein [ Time Frame: Baseline, Week 32 ] [ Designated as safety issue: No ]
    Duration in days in the study to the first minimum adapted ACR Pediatric 50 criteria and a normal (<10mg/L) C-Reactive Protein

  • Part I: Time to First Minimum American College of Rheumatology (ACR70) and Normal C-Reactive Protein [ Time Frame: Baseline, Week 32 ] [ Designated as safety issue: No ]
    Duration in days in the study to the first minimum adapted ACR Pediatric 70 criteria and a normal (<10mg/L) C-Reactive Protein

  • Part I: Percentage of Participants With Body Temperature ≤ 38 Degrees Celsius at Day 3 in Part 1a [ Time Frame: Day 3 ] [ Designated as safety issue: No ]
  • Part II: Survival Analysis of Time to a Worsening in American College of Rheumatology (ACR) Response [ Time Frame: Part II was event driven. The study was stopped when the required number of 37 flares had occurred (88 weeks) ] [ Designated as safety issue: No ]

    Kaplan Meier estimate of the time in days to the probability of worsening of the ACR response.

    ACR response is determined by the following items:

    1. Physician's global assessment of disease activity
    2. CHAQ-patient's overall wellbeing
    3. CHAQ-Functional ability
    4. Number of joints with active arthritis
    5. Number of joints with limitation of motion
    6. C-Reactive Protein.
    7. No intermittent fever in the preceding week

  • Part I: Change in Disability Over Time in the Child Health Assessment Questionnaire-Disability Index (CHAQ-DI) From Baseline to End of Part I [ Time Frame: Baseline, End of Part I (Week 32) ] [ Designated as safety issue: No ]
    The childhood health assessment questionnaire, CHAQ was used to assess physical ability and functional status of patients as well as quality of life. The disability dimension consists of 20 multiple choice items concerning difficulty in performing eight common activities of daily living; dressing and grooming, arising, eating, walking, reaching, personal hygiene, gripping and other "activities". Parents choose from four response categories, ranging from 0(without any difficulty) to 3(unable to do). A negative change indicates improvement.

  • Part II: Change in Disability Over Time by the Child Health Assessment Questionnaire-Disability Index (CHAQ-DI) [ Time Frame: Start of Part II (Week 32), End of Part II ( total duration-88 weeks) ] [ Designated as safety issue: No ]

    CHAQ-DI assessed physical ability and functional status of patients and quality of life. 20 multiple choice items concerning difficulty in performing 8 common activities of daily living; dressing and grooming, arising, eating, walking, reaching, personal hygiene, gripping and other "activities". Parents choose from 4 response categories, ranging from 0(without any difficulty) to 3(unable to do).

    Repeated measures Analysis of Covariance with treatment group, visit day, prednisone (or equivalent) dose and adapted ACR 70 response reached at the end of Part Id as covariates.


  • Part I: Change in Health Related Quality of Life Over Time by Child Health Questionnaire (CHQ-PF50) [ Time Frame: Baseline, End of Part I ( Week 32) ] [ Designated as safety issue: No ]
    The CHQ-PF50© is an instrument used to measure Health Related Quality of Life in children 5-18 from the parent's perspective. The questionnaire measures the following concepts: Physical functioning, Role/social emotional, Role/social behavior, Role/social physical, Bodily pain, General behavior, Mental health, Self-esteem, General health perception, Change in health, Parental impact - emotional, Parental impact - time, Family activities, and Family cohesion. Summaries are provided for Physical Health and Psychosocial Health. Scores range from 0-100. Increase in score represents improvement.

  • Part II: Change in Health Related Quality of Life Over Time by Child Health Questionnaire (CHQ-PF50) [ Time Frame: Start Part II (Week 32), End Part II (total duration - 88 Weeks) ] [ Designated as safety issue: No ]
    CHQ-PF50 measures Physical functioning, Role/social emotional, behavior and physical, Bodily pain, General behavior, Mental health, Self-esteem, General health perception, Change in health, Parental impact-emotional, Parental impact-time, Family activities and cohesion. Summaries are provided for Physical Health and Psychosocial Health. An increase in score indicates improvement. Repeated measures Analysis of Covariance change from start of Part II with treatment group, visit day, prednisone(or equivalent) dose and adapted ACR70 Pediatric response reached at the end of Part Id as covariates.


Enrollment: 177
Study Start Date: July 2009
Study Completion Date: September 2011
Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Canakinumab
In Part I participants received open label 4 mg/kg canakinumab subcutaneous injection every 4 weeks for up to 32 weeks. For the first 8 weeks Part Ia (4 weeks) and Ib (4 weeks) patients maintained a stable oral steroid dose (prednisone or equivalent) followed by Ic an up to 20 week steroid tapering period and then Id a 4 week stable steroid dose period. Participants were then randomized to receive either 4 mg/kg canakinumab subcutaneous injection or placebo comparator in Part II and remained on the stable oral steroid dose for 24 weeks. At 24 weeks in Part II participants with a >0.2 mg/kg and ≤ 0.5 mg/kg and no flare could restart steroid tapering. If the steroid dose was ≤ 0.2 mg/kg participants continued to maintain their current dose for the remainder of Part II.
Drug: canakinumab
Canakinumab 4 mg/kg dose subcutaneous injection supplied as 6 mL glass vials each containing 150 mg canakinumab as a lyophilized cake.
Placebo Comparator: Placebo
Participants in Part II received placebo matching canakinumab subcutaneous injection every 4 weeks. At 24 weeks in Part II participants with a >0.2 mg/kg and ≤0.5 mg/kg and no flare could restart steroid tapering. If the steroid dose was ≤0.2 mg/kg participants continued to maintain their current dose for the remainder of Part II.
Drug: placebo
Placebo powder matching canakinumab supplied as 6 mL glass vials containing a lyophilized cake for subcutaneous injection every 4 weeks in Part II.

  Eligibility

Ages Eligible for Study:   2 Years to 19 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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

  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: NCT00889863

  Hide Study Locations
Locations
United States, Arkansas
Arkansas Children's Hospital Research Inst
Little Rock, Arkansas, United States, 72202
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
New England Medical Center - Department 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
Cincinnati, Ohio, United States, 45229
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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Curitiba, Brazil
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Porto Alegre, Brazil
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Rio de Janiero, Brazil
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Sao Paulo, Brazil
Canada, British Columbia
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Vancouver, British Columbia, Canada
Canada, Nova Scotia
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Halifax, Nova Scotia, Canada
Canada, Ontario
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Toronto, Ontario, Canada
Canada, Quebec
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Montreal, Quebec, Canada
France
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Le Kremlin Bicetre, France
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Lyon, France
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Paris, France
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Strasbourg, France
Germany
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Bad Bamstedt, Germany
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Berlin, Germany
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Bremen, Germany
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Freiburg, Germany
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Geissen, Germany
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Hamburg, Germany
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Muenster, Germany
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Saint Augustin, Germany
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Stuttgart, Germany
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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Johannesburg, 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
Sponsors and Collaborators
Novartis Pharmaceuticals
Pediatric Rheumatology International Trials Organization
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: NCT00889863     History of Changes
Other Study ID Numbers: CACZ885G2301, EudraCT: 2008-005479-82
Study First Received: April 21, 2009
Results First Received: September 12, 2012
Last Updated: September 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: Lægemiddelstyrelsen

Keywords provided by Novartis:
Flare
arthritis
IL-1beta antagonist
systemic juvenile idiopathic arthritis
Juvenile rheumatoid

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 September 18, 2014