AzTrials
AzTrials

Systemic Juvenile Idiopathic Arthritis With Active FlarePhase 3β-SPECIFIC 2NCT00889863

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

A Phase 3 study testing canakinumab in people with Systemic Juvenile Idiopathic Arthritis With Active Flare, run by Novartis Pharmaceuticals at 73 sites in 19 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 2 to 19 years
What is being tested?
canakinumab
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
177 participants
Where
73 sitesin 19 countries
Study dates
Jul 2009to Sep 2011
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 2 to 19 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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)
Show all 10Show fewer
  • 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

Who cannot join

  • 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 locations and contacts

73 sites in 19 countries.

73 sites in 19 countries

United States12 sites
  • Specially For Children

    Austin, Texas, 78723

  • New England Medical Center - Department of Allergy

    Boston, Massachusetts, 02111

  • Tufts Medical Center

    Boston, Massachusetts, 02111

  • University of Chicago Medical Center

    Chicago, Illinois, 60637

  • Children's Hospital Medical Center

    Cincinnati, Ohio, 45229

  • Children's Hospital/Neurology

    Cincinnati, Ohio, 45229

  • Arkansas Children's Hospital Research Inst

    Little Rock, Arkansas, 72202

  • St Barnabas Ambulatory Care Center

    Livingston, New Jersey, 07039

  • University of Louisville

    Louisville, Kentucky, 40202

  • Legacy Emanuel Hospital

    Portland, Oregon, 97227

  • Legacy Emanual Research

    Portland, Oregon, 97232

  • Children's National Medical Center

    Washington D.C., District of Columbia, 20010

Other trials in United States

Germany9 sites
  • Novartis Investigative Site

    Bad Bamstedt

  • Novartis Investigative site

    Berlin

  • Novartis Investigative Site

    Bremen

  • Novartis Investigative Site

    Freiburg im Breisgau

  • Novartis Investigative Site

    Geißen

  • Novartis Investigative Site

    Hamburg

  • Novartis Investigative Site

    Münster

  • Novartis Investigative Site

    Saint Augustin

  • Novartis Investigative Site

    Stuttgart

Other trials in Germany

Italy9 sites
  • Novartis Investigative Site

    Bologna

  • Novartis Investigative Site

    Florence

  • Novartis Investigative Site

    Genova

  • Novartis Investigative site

    Milan

  • Novartis Investigative site

    Naples

  • Novartis Investigative site

    Padova

  • Novartis Investigative site

    Rome

  • Novartis Investigative site

    Scafati

  • Novartis Investigative site

    Torino

Other trials in Italy

Israel5 sites
  • Novartis Investigative Site

    Haifa

  • Novartis Investigative Site

    Kfar Saba

  • Novartis Investigative Site

    Petah Tikva

  • Novartis Investigative Site

    Ramat Gan

  • Novartis Investigative Site

    Rehovot

Other trials in Israel

Belgium4 sites
  • Novartis Investigative site

    Brussels

  • Novartis Investigative site

    Ghent

  • Novartis Investigative Site

    Laken

  • Novartis Investigative site

    Leuven

Other trials in Belgium

Brazil4 sites
  • Novartis Investigative Site

    Curitiba

  • Novartis Investigative site

    Porto Alegre

  • Novartis Investigative site

    Rio de Janiero

  • Novartis Investigative site

    São Paulo

Other trials in Brazil

Canada4 sites
  • Novartis Investigative site

    Halifax, Nova Scotia

  • Novartis Investigative site

    Montreal, Quebec

  • Novartis Investigative site

    Toronto, Ontario

  • Novartis Investigative site

    Vancouver, British Columbia

Other trials in Canada

France4 sites
  • Novartis Investigative Site

    Le Kremlin-Bicêtre

  • Novartis Investigative Site

    Lyon

  • Novartis Investigative Site

    Paris

  • Novartis Investigative Site

    Strasbourg

Other trials in France

South Africa4 sites
  • Novartis Investigative site

    Berea, Durban

  • Novartis Investigative site

    Johannesburg

  • Novartis Investigative site

    Mayville, Durban

  • Novartis Investigative site

    Pretoria

Other trials in South Africa

Argentina3 sites
  • Novartis Investigative Site

    Buenos Aires

  • Novartis Investigative Site

    Capital Federal

  • Novartis Investigative Site

    La Plata

Other trials in Argentina

Spain3 sites
  • Novartis Investigative site

    Barcelona

  • Novartis Investigative site

    Madrid

  • Novartis Investigative site

    Valencia

Other trials in Spain

Switzerland3 sites
  • Novartis Investigative Site

    Bern

  • Novartis Investigative site

    Lausanne

  • Novartis Investigative site

    Zurich

Other trials in Switzerland

Turkey (Türkiye)3 sites
  • Novartis Investigative site

    Ankara

  • Novartis Investigative Site

    Istanbul

  • Novartis Investigative Site

    Izmir

Other trials in Turkey (Türkiye)

Hungary1 site
  • Novartis Investigative Site

    Budapest

Other trials in Hungary

Netherlands1 site
  • Novartis Investigative site

    Utrecht

Other trials in Netherlands

Norway1 site
  • Novartis Investigative Site

    Oslo

Other trials in Norway

Peru1 site
  • Novartis Investigative Site

    Lima

Other trials in Peru

Poland1 site
  • Novartis Investigative site

    Warsaw

Other trials in Poland

Sweden1 site
  • Novartis Investigative site

    Stockholm

Other trials in Sweden

About this study

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

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.

Being tested
canakinumab, placebo
Keywords
Flare, arthritis, IL-1beta antagonist, systemic juvenile idiopathic arthritis, Juvenile rheumatoid
Medical subject headings
Arthritis, Arthritis, Juvenile

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 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.

Study groups in NCT00889863
Study groupRoleWhat they receive
CanakinumabExperimentalIn 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.
Receives: Drug: canakinumab
PlaceboPlacebo comparatorParticipants 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.
Receives: Drug: placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 32 Weeks

  2. 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.

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

Secondary outcomes (11)
  1. Part I: Percentage of Patients on Steroids at Study Start Who Reached a Steroid Dose ≤0.2 mg/kg at End of Part Ic

    Measured: 28 Weeks

  2. Part I: Percentage of Participants on Steroids at the Start of 1c Who Were Able to Taper Steroids by the End of Part 1c

    Measured: Start of Part Ic (After Week 8) to End of Part Ic (Week 28)

  3. 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%

    Measured: Baseline, 32 Weeks

  4. Part I: Time to First Minimum American College of Rheumatology (ACR50) and Normal C-Reactive Protein

    Duration in days in the study to the first minimum adapted ACR Pediatric 50 criteria and a normal (<10mg/L) C-Reactive Protein

    Measured: Baseline, Week 32

  5. Part I: Time to First Minimum American College of Rheumatology (ACR70) and Normal C-Reactive Protein

    Duration in days in the study to the first minimum adapted ACR Pediatric 70 criteria and a normal (<10mg/L) C-Reactive Protein

    Measured: Baseline, Week 32

  6. Part I: Percentage of Participants With Body Temperature ≤ 38 Degrees Celsius at Day 3 in Part 1a

    Measured: Day 3

  7. Part II: Survival Analysis of Time to a Worsening in American College of Rheumatology (ACR) Response

    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

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

  8. Part I: Change in Disability Over Time in the Child Health Assessment Questionnaire-Disability Index (CHAQ-DI) From Baseline to End of Part I

    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.

    Measured: Baseline, End of Part I (Week 32)

  9. Part II: Change in Disability Over Time by the Child Health Assessment Questionnaire-Disability Index (CHAQ-DI)

    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.

    Measured: Start of Part II (Week 32), End of Part II ( total duration-88 weeks)

  10. Part I: Change in Health Related Quality of Life Over Time by Child Health Questionnaire (CHQ-PF50)

    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.

    Measured: Baseline, End of Part I ( Week 32)

  11. Part II: Change in Health Related Quality of Life Over Time by Child Health Questionnaire (CHQ-PF50)

    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.

    Measured: Start Part II (Week 32), End Part II (total duration - 88 Weeks)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Apr 2009 (estimated)
  2. Study startJul 2009
  3. Primary completionSep 2011
  4. Study completionSep 2011

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
177 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00889863
Sponsor's protocol ID
CACZ885G2301
Other IDs
EudraCT: 2008-005479-82
Acronym
β-SPECIFIC 2
Status last verified
Sep 2012
First submitted
21 Apr 2009
Last updated
16 Oct 2012

Publications

  • 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.

    PubMed 30269054
  • 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.

    PubMed 28115015
  • 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.

    PubMed 26314396
  • 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.

    PubMed 23252526

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing canakinumab in people with Systemic Juvenile Idiopathic Arthritis With Active Flare, run by Novartis Pharmaceuticals at 73 sites in 19 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 16 Oct 2012. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 73 sites in United States, Germany, Italy, Israel, Belgium and 14 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 16 Oct 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00889863, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Oct 2012.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in