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

Novartis Pharmaceuticals177 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

177

Conditions

Systemic Juvenile Idiopathic Arthritis With Active Flare

Interventions

canakinumabDRUG

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

placeboDRUG

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

Eligibility

Sex: ALLMin age: 2 YearsMax age: 19 Years

Medical Language ↔ Plain English

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

Locations (73)

Outcomes

Primary Outcomes

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

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.

Time frame: 32 Weeks

Part II: Survival Estimate of Time to Flare

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.

Time frame: Part II was event driven. The study was stopped when the required number of 37 flares had occurred (88 weeks)

Secondary Outcomes

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

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)

Part I: Percentage of Participants With Minimum American College of Rheumatology (ACR) 30/50/70/90/100 at the End of Part I

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%

Data from ClinicalTrials.gov

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Arkansas Children's Hospital Research Inst

Little Rock, Arkansas, United States

Children's National Medical Center

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

University of Chicago Medical Center

Chicago, Illinois, United States

University of Louisville

Louisville, Kentucky, United States

New England Medical Center - Department of Allergy

Boston, Massachusetts, United States

Tufts Medical Center

Boston, Massachusetts, United States

St Barnabas Ambulatory Care Center

Livingston, New Jersey, United States

Children's Hospital Medical Center

Cincinnati, Ohio, United States

Children's Hospital/Neurology

Cincinnati, Ohio, United States

Legacy Emanuel Hospital

Portland, Oregon, United States

...and 63 more locations