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

Novartis

Status and phase: Completed; Phase 3

Conditions: Systemic Juvenile Idiopathic Arthritis With Active Flare

Treatments: Drug: placebo; Drug: canakinumab

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT00889863

EudraCT: 2008-005479-82

CACZ885G2301

Details and patient eligibility

About

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.

Enrollment: 177 patients

Sex: All

Ages: 2 to 19 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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177 participants in 2 patient groups, including a placebo group

Canakinumab

Experimental group

Description:

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.

Treatment:

Drug: canakinumab

Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: placebo