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
Results First Received: September 12, 2012  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Systemic Juvenile Idiopathic Arthritis With Active Flare
Interventions: Drug: canakinumab
Drug: placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
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.
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.

Participant Flow for 2 periods

Period 1:   Part I: Open Label
    Canakinumab     Placebo  
STARTED     177     0 [1]
Entered Part Ia     145     0  
Entered Part Ib     142     0  
Entered Part Ic     92 [2]   0  
Entered Part 1d     103     0  
COMPLETED     100     0  
NOT COMPLETED     77     0  
Death                 1                 0  
Adverse Event                 4                 0  
Unsatisfactory therapeutic effect                 72                 0  
[1] No participants received placebo in Part I.
[2] Patients steroid free at study entry entered Part Id directly and did not participate in Part Ic.

Period 2:   Part II: Randomized Double Blind
    Canakinumab     Placebo  
STARTED     50     50  
COMPLETED     39     24  
NOT COMPLETED     11     26  
Adverse Event                 0                 4  
Unsatisfactory therapeutic effect                 11                 20  
Withdrawal by Subject                 0                 1  
Protocol deviation                 0                 1  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
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.

Baseline Measures
    Canakinumab  
Number of Participants  
[units: participants]
  177  
Age  
[units: years]
Mean ± Standard Deviation
  8.7  ± 4.46  
Gender  
[units: participants]
 
Female     98  
Male     79  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   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 ]

2.  Primary:   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) ]

3.  Secondary:   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 ]

4.  Secondary:   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) ]

5.  Secondary:   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 ]

6.  Secondary:   Part I: Time to First Minimum American College of Rheumatology (ACR50) and Normal C-Reactive Protein   [ Time Frame: Baseline, Week 32 ]

7.  Secondary:   Part I: Time to First Minimum American College of Rheumatology (ACR70) and Normal C-Reactive Protein   [ Time Frame: Baseline, Week 32 ]

8.  Secondary:   Part I: Percentage of Participants With Body Temperature ≤ 38 Degrees Celsius at Day 3 in Part 1a   [ Time Frame: Day 3 ]

9.  Secondary:   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) ]

10.  Secondary:   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) ]

11.  Secondary:   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) ]

12.  Secondary:   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) ]

13.  Secondary:   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) ]


  Serious Adverse Events
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Reporting Groups
  Description
Canakinumab: Part I 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.
Canakinumab: Part II Participants received 4 mg/kg canakinumab subcutaneous injection 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.
Placebo: Part II 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.

Serious Adverse Events
    Canakinumab: Part I     Canakinumab: Part II     Placebo: Part II  
Total, serious adverse events        
# participants affected / at risk     15/177 (8.47%)     6/50 (12.00%)     6/50 (12.00%)  
Blood and lymphatic system disorders        
Anaemia † 1      
# participants affected / at risk     1/177 (0.56%)     0/50 (0.00%)     0/50 (0.00%)  
Lymphadenopathy † 1      
# participants affected / at risk     0/177 (0.00%)     1/50 (2.00%)     0/50 (0.00%)  
Cardiac disorders        
Cardiac arrest † 1      
# participants affected / at risk     0/177 (0.00%)     0/50 (0.00%)     1/50 (2.00%)  
Gastrointestinal disorders        
Abdominal pain † 1      
# participants affected / at risk     2/177 (1.13%)     0/50 (0.00%)     0/50 (0.00%)  
Vomiting † 1      
# participants affected / at risk     2/177 (1.13%)     0/50 (0.00%)     0/50 (0.00%)  
Abdominal pain upper † 1      
# participants affected / at risk     1/177 (0.56%)     0/50 (0.00%)     0/50 (0.00%)  
Diarrhoea † 1      
# participants affected / at risk     1/177 (0.56%)     0/50 (0.00%)     0/50 (0.00%)  
Nausea † 1      
# participants affected / at risk     1/177 (0.56%)     0/50 (0.00%)     0/50 (0.00%)  
Oral disorder † 1      
# participants affected / at risk     0/177 (0.00%)     0/50 (0.00%)     1/50 (2.00%)  
General disorders        
Pyrexia † 1      
# participants affected / at risk     3/177 (1.69%)     0/50 (0.00%)     0/50 (0.00%)  
Fatigue † 1      
# participants affected / at risk     1/177 (0.56%)     0/50 (0.00%)     0/50 (0.00%)  
Medical device complication † 1      
# participants affected / at risk     1/177 (0.56%)     0/50 (0.00%)     0/50 (0.00%)  
Hepatobiliary disorders        
Hepatitis † 1      
# participants affected / at risk     1/177 (0.56%)     0/50 (0.00%)     0/50 (0.00%)  
Immune system disorders        
Drug hypersensitivity † 1      
# participants affected / at risk     1/177 (0.56%)     0/50 (0.00%)     0/50 (0.00%)  
Infections and infestations        
Acute sinusitis † 1      
# participants affected / at risk     1/177 (0.56%)     0/50 (0.00%)     0/50 (0.00%)  
Adenovirus infection † 1      
# participants affected / at risk     1/177 (0.56%)     0/50 (0.00%)     0/50 (0.00%)  
Gastroenteritis † 1      
# participants affected / at risk     1/177 (0.56%)     0/50 (0.00%)     0/50 (0.00%)  
Gastrointestinal infection † 1      
# participants affected / at risk     1/177 (0.56%)     0/50 (0.00%)     0/50 (0.00%)  
Gastrointestinal viral infection † 1      
# participants affected / at risk     1/177 (0.56%)     0/50 (0.00%)     0/50 (0.00%)  
Lobar pneumonia † 1      
# participants affected / at risk     1/177 (0.56%)     0/50 (0.00%)     0/50 (0.00%)  
Lymph node abscess † 1      
# participants affected / at risk     1/177 (0.56%)     0/50 (0.00%)     0/50 (0.00%)  
Pharyngitis † 1      
# participants affected / at risk     1/177 (0.56%)     0/50 (0.00%)     0/50 (0.00%)  
Pneumonia † 1      
# participants affected / at risk     1/177 (0.56%)     0/50 (0.00%)     1/50 (2.00%)  
Otitis media † 1      
# participants affected / at risk     0/177 (0.00%)     1/50 (2.00%)     0/50 (0.00%)  
Respiratory tract infection † 1      
# participants affected / at risk     0/177 (0.00%)     1/50 (2.00%)     0/50 (0.00%)  
Measles † 1      
# participants affected / at risk     0/177 (0.00%)     0/50 (0.00%)     1/50 (2.00%)  
Sepsis † 1      
# participants affected / at risk     0/177 (0.00%)     0/50 (0.00%)     1/50 (2.00%)  
Septic shock † 1      
# participants affected / at risk     0/177 (0.00%)     0/50 (0.00%)     1/50 (2.00%)  
Injury, poisoning and procedural complications        
Femur fracture † 1      
# participants affected / at risk     0/177 (0.00%)     1/50 (2.00%)     0/50 (0.00%)  
Post procedural haemorrhage † 1      
# participants affected / at risk     0/177 (0.00%)     1/50 (2.00%)     0/50 (0.00%)  
Traumatic fracture † 1      
# participants affected / at risk     0/177 (0.00%)     1/50 (2.00%)     1/50 (2.00%)  
Forearm fracture † 1      
# participants affected / at risk     0/177 (0.00%)     0/50 (0.00%)     1/50 (2.00%)  
Investigations        
C-reactive protein increased † 1      
# participants affected / at risk     1/177 (0.56%)     0/50 (0.00%)     0/50 (0.00%)  
Coagulation test abnormal † 1      
# participants affected / at risk     1/177 (0.56%)     0/50 (0.00%)     0/50 (0.00%)  
Hepatic enzyme increased † 1      
# participants affected / at risk     1/177 (0.56%)     1/50 (2.00%)     0/50 (0.00%)  
Platelet count increased † 1      
# participants affected / at risk     1/177 (0.56%)     0/50 (0.00%)     0/50 (0.00%)  
Serum ferritin increased † 1      
# participants affected / at risk     1/177 (0.56%)     0/50 (0.00%)     0/50 (0.00%)  
White blood cell count increased † 1      
# participants affected / at risk     1/177 (0.56%)     0/50 (0.00%)     0/50 (0.00%)  
Alanine aminotransferase increased † 1      
# participants affected / at risk     0/177 (0.00%)     1/50 (2.00%)     0/50 (0.00%)  
Aspartate aminotransferase increased † 1      
# participants affected / at risk     0/177 (0.00%)     1/50 (2.00%)     0/50 (0.00%)  
Haptoglobin decreased † 1      
# participants affected / at risk     0/177 (0.00%)     1/50 (2.00%)     0/50 (0.00%)  
Platelet count decreased † 1      
# participants affected / at risk     0/177 (0.00%)     1/50 (2.00%)     0/50 (0.00%)  
White blood cell count decreased † 1      
# participants affected / at risk     0/177 (0.00%)     1/50 (2.00%)     0/50 (0.00%)  
Musculoskeletal and connective tissue disorders        
Juvenile arthritis † 1      
# participants affected / at risk     2/177 (1.13%)     0/50 (0.00%)     2/50 (4.00%)  
Arthralgia † 1      
# participants affected / at risk     1/177 (0.56%)     0/50 (0.00%)     0/50 (0.00%)  
Arthritis † 1      
# participants affected / at risk     1/177 (0.56%)     0/50 (0.00%)     0/50 (0.00%)  
Pain in extremity † 1      
# participants affected / at risk     0/177 (0.00%)     1/50 (2.00%)     0/50 (0.00%)  
Neoplasms benign, malignant and unspecified (incl cysts and polyps)        
Histiocytosis haematophagic † 1      
# participants affected / at risk     4/177 (2.26%)     0/50 (0.00%)     1/50 (2.00%)  
Splenic neoplasm malignancy unspecified † 1      
# participants affected / at risk     0/177 (0.00%)     1/50 (2.00%)     0/50 (0.00%)  
Nervous system disorders        
Headache † 1      
# participants affected / at risk     1/177 (0.56%)     0/50 (0.00%)     0/50 (0.00%)  
Paraesthesia † 1      
# participants affected / at risk     1/177 (0.56%)     0/50 (0.00%)     0/50 (0.00%)  
Posterior reversible encephalopathy syndrome † 1      
# participants affected / at risk     1/177 (0.56%)     0/50 (0.00%)     0/50 (0.00%)  
Somnolence † 1      
# participants affected / at risk     1/177 (0.56%)     0/50 (0.00%)     0/50 (0.00%)  
Psychiatric disorders        
Anxiety † 1      
# participants affected / at risk     2/177 (1.13%)     0/50 (0.00%)     0/50 (0.00%)  
Renal and urinary disorders        
Renal colic † 1      
# participants affected / at risk     0/177 (0.00%)     0/50 (0.00%)     1/50 (2.00%)  
Respiratory, thoracic and mediastinal disorders        
Hyperventilation † 1      
# participants affected / at risk     1/177 (0.56%)     0/50 (0.00%)     0/50 (0.00%)  
Interstitial lung disease † 1      
# participants affected / at risk     1/177 (0.56%)     0/50 (0.00%)     0/50 (0.00%)  
Lung consolidation † 1      
# participants affected / at risk     1/177 (0.56%)     0/50 (0.00%)     0/50 (0.00%)  
Pulmonary hypertension † 1      
# participants affected / at risk     1/177 (0.56%)     0/50 (0.00%)     0/50 (0.00%)  
Adenoidal hypertrophy † 1      
# participants affected / at risk     0/177 (0.00%)     1/50 (2.00%)     0/50 (0.00%)  
Respiratory failure † 1      
# participants affected / at risk     0/177 (0.00%)     0/50 (0.00%)     1/50 (2.00%)  
Skin and subcutaneous tissue disorders        
Rash maculo-papular † 1      
# participants affected / at risk     0/177 (0.00%)     0/50 (0.00%)     1/50 (2.00%)  
Events were collected by systematic assessment
1 Term from vocabulary, MedDRA 14.0




  Other Adverse Events


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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Limitations and Caveats
Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.  


Results Point of Contact:  
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
phone: 862-778-8300


No publications provided by Novartis

Publications automatically indexed to this study:

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