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

NCT ID: NCT00889863

Last Updated: 2012-10-16

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

177 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-07-31

Study Completion Date

2011-09-30

Brief Summary

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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.

Detailed Description

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Conditions

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Systemic Juvenile Idiopathic Arthritis With Active Flare

Keywords

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Flare arthritis IL-1beta antagonist systemic juvenile idiopathic arthritis Juvenile rheumatoid

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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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.

Group Type EXPERIMENTAL

canakinumab

Intervention Type DRUG

Canakinumab 4 mg/kg dose subcutaneous injection supplied as 6 mL glass vials each containing 150 mg canakinumab as a lyophilized cake.

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.

Group Type PLACEBO_COMPARATOR

placebo

Intervention Type DRUG

Placebo powder matching canakinumab supplied as 6 mL glass vials containing a lyophilized cake for subcutaneous injection every 4 weeks in Part II.

Interventions

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canakinumab

Canakinumab 4 mg/kg dose subcutaneous injection supplied as 6 mL glass vials each containing 150 mg canakinumab as a lyophilized cake.

Intervention Type 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.

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

2 Years

Maximum Eligible Age

19 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Pediatric Rheumatology International Trials Organization

OTHER

Sponsor Role collaborator

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

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Arkansas Children's Hospital Research Inst

Little Rock, Arkansas, United States

Site Status

Children's National Medical Center

Washington D.C., District of Columbia, United States

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University of Chicago Medical Center

Chicago, Illinois, United States

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University of Louisville

Louisville, Kentucky, United States

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New England Medical Center - Department of Allergy

Boston, Massachusetts, United States

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Tufts Medical Center

Boston, Massachusetts, United States

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St Barnabas Ambulatory Care Center

Livingston, New Jersey, United States

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Children's Hospital Medical Center

Cincinnati, Ohio, United States

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Children's Hospital/Neurology

Cincinnati, Ohio, United States

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Legacy Emanuel Hospital

Portland, Oregon, United States

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Legacy Emanual Research

Portland, Oregon, United States

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Specially For Children

Austin, Texas, United States

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Novartis Investigative Site

Buenos Aires, , Argentina

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Capital Federal, , Argentina

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La Plata, , Argentina

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Brussels, , Belgium

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Ghent, , Belgium

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Laken, , Belgium

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Leuven, , Belgium

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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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São Paulo, , Brazil

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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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Le Kremlin-Bicêtre, , France

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Lyon, , France

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Paris, , France

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Strasbourg, , France

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Bad Bamstedt, , Germany

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Berlin, , Germany

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Bremen, , Germany

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Freiburg im Breisgau, , Germany

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Geißen, , Germany

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Hamburg, , Germany

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Münster, , Germany

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Saint Augustin, , Germany

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Stuttgart, , Germany

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Budapest, , Hungary

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Haifa, , Israel

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Kfar Saba, , Israel

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Petah Tikva, , Israel

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Ramat Gan, , Israel

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Rehovot, , Israel

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Bologna, , Italy

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Florence, , Italy

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Genova, , Italy

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Milan, , Italy

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Napoli, , Italy

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Padua, , Italy

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Rome, , Italy

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Scafati, , Italy

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Torino, , Italy

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Utrecht, , Netherlands

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Oslo, , Norway

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Lima, , Peru

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Warsaw, , Poland

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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

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Barcelona, , Spain

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Madrid, , Spain

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Valencia, , Spain

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Stockholm, , Sweden

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Bern, , Switzerland

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Lausanne, , Switzerland

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Zurich, , Switzerland

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Ankara, , Turkey (Türkiye)

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Novartis Investigative Site

Istanbul, , Turkey (Türkiye)

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Novartis Investigative Site

Izmir, , Turkey (Türkiye)

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Countries

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United States Argentina Belgium Brazil Canada France Germany Hungary Israel Italy Netherlands Norway Peru Poland South Africa Spain Sweden Switzerland Turkey (Türkiye)

References

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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.

Reference Type DERIVED
PMID: 30269054 (View on PubMed)

Brachat AH, Grom AA, Wulffraat N, Brunner HI, Quartier P, Brik R, McCann L, Ozdogan H, Rutkowska-Sak L, Schneider R, Gerloni V, Harel L, Terreri M, Houghton K, Joos R, Kingsbury D, Lopez-Benitez JM, Bek S, Schumacher M, Valentin MA, Gram H, Abrams K, Martini A, Lovell DJ, Nirmala NR, Ruperto N; Pediatric Rheumatology International Trials Organization (PRINTO) and the Pediatric Rheumatology Collaborative Study Group (PRCSG). Early changes in gene expression and inflammatory proteins in systemic juvenile idiopathic arthritis patients on canakinumab therapy. Arthritis Res Ther. 2017 Jan 23;19(1):13. doi: 10.1186/s13075-016-1212-x.

Reference Type DERIVED
PMID: 28115015 (View on PubMed)

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.

Reference Type DERIVED
PMID: 26314396 (View on PubMed)

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.

Reference Type DERIVED
PMID: 23252526 (View on PubMed)

Related Links

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Other Identifiers

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EudraCT: 2008-005479-82

Identifier Type: -

Identifier Source: secondary_id

CACZ885G2301

Identifier Type: -

Identifier Source: org_study_id