Systemic Juvenile Idiopathic ArthritisPhase 3β-SPECIFIC 3NCT00891046
An Open-label Extension Study of Canakinumab in Patients With Systemic Juvenile Idiopathic Arthritis and Active Systemic Manifestations Manifestations and Response Characterization Study in Canakinumab Treatment-naïve Patients With Active SJIA With and Without Fever.
A Phase 3 study testing Canakinumab in people with Systemic Juvenile Idiopathic Arthritis, run by Novartis Pharmaceuticals at 73 sites in 21 countries.
Trial summary
This open-label extension study will permit patients with Systemic Juvenile Idiopathic Arthritis (SJIA) who previously were responsive to treatment with canakinumab and canakinumab treatment-naïve patients with active SJIA with and without fever to be retreated with 4 mg/kg s.c. Read more about this study
- Who is it for?
- Ages 2 to 19 years
- Conditions the study is for
- Systemic Juvenile Idiopathic Arthritis
- What is being tested?
- Canakinumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 270 participants
- Where
- 73 sitesin 21 countries
- Study dates
- Sep 2009to Dec 2014
- 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
- Patients from study CACZ885G2305 or CACZ885G2301 who achieved an adapted ACR pediatric 30 response 15 days after their initial dose of canakinumab but clinically deteriorated afterwards or a minimum ACR Pediatric 30 response was not maintained after Day 15 and intervention is deemed necessary by the investigator, or Patients in study CACZ885G2301 who are not eligible to enter Part II (withdrawal part) because they were not able to meet the corticosteroid entry criteria , or Responder patients in Part I or Part II who had not flared when CACZ885G2301 was stopped, or CACZ885G2301 patients who were responders in Part I but experienced a flare in Part II.
- Treatment-naïve patients need to meet the following criteria:
- Confirmed diagnosis of systemic juvenile idiopathic arthritis as per ILAR definition that must have occurred at least 2 months prior to enrollment with onset of disease < 16 years of age
- Male and female patients aged ≥ 2 to < 20 years of age
- Active disease at the time of enrollment defined as having 2 or more of the following:
- Documented spiking, intermittent fever (body temperature > 38°C) for at least 1 day during the screening period and within 1 week before first canakinumab dose
Show all 10Show fewer
- At least 2 joints with active arthritis
- AND C-reactive protein (CRP) > 30 mg/L (normal range < 10 mg/L) Rash Serositis Lymphadenopathy Hepatosplenomegaly
- Naïve to canakinumab
- Other protocol-defined inclusion criteria may apply
Who cannot join
- History of allergy or hypersensitivity to study drug
- With active or recurrent bacterial, fungal or viral infections at time of enrollment
- Other protocol inclusion/exclusion criteria may apply
Trial locations and contacts
73 sites in 21 countries.
73 sites in 21 countries
Germany13 sites
Novartis Investigative Site
Bad Bramstedt, 24576
Novartis Investigative Site
Berlin, 13125
Novartis Investigative Site
Berlin, 13353
Novartis Investigative Site
Freiburg im Breisgau, 79106
Novartis Investigative Site
Garmisch-Partenkirchen, 82467
Novartis Investigative Site
Giessen, 35392
Novartis Investigative Site
Hamburg, 20246
Novartis Investigative Site
Hamburg, 22081
Novartis Investigative Site
Hanover, 30625
Novartis Investigative Site
Heidelberg, 69120
Novartis Investigative Site
Münster, 48149
Novartis Investigative Site
Saint Augustin, 53757
Novartis Investigative Site
Tübingen, 72076
United Kingdom7 sites
Novartis Investigative Site
Bath, BS2 8BJ
Novartis Investigative Site
Birmingham, B4 6NH
Novartis Investigative Site
Liverpool, L12 2AP
Novartis Investigative Site
London, WC1N 1EH
Novartis Investigative Site
Manchester, M9 2AA
Novartis Investigative Site
Newcastle Upon Tyme, NE4 4LP
Novartis Investigative Site
Oxford, OX3 7LD
United States6 sites
Novartis Investigative Site
Boston, Massachusetts, 02111
Novartis Investigative Site
Cincinnati, Ohio, 45229
Novartis Investigative Site
Columbus, Ohio, 43205
Novartis Investigative Site
Los Angeles, California, 90027
Novartis Investigative Site
Louisville, Kentucky, 40202
Novartis Investigative Site
Portland, Oregon, 97232
Israel5 sites
Novartis Investigative Site
Haifa, 31096
Novartis Investigative Site
Kfar Saba, 4428164
Novartis Investigative Site
Petah Tikva, 49202
Novartis Investigative Site
Ramat Gan, 5266202
Novartis Investigative Site
Rehovot, 76100
Italy5 sites
Novartis Investigative Site
Florence, FI, 50132
Novartis Investigative Site
Genova, GE, 16147
Novartis Investigative Site
Milan, MI, 20100
Novartis Investigative Site
Milan, MI, 20122
Novartis Investigative Site
Naples, 80131
Belgium4 sites
Novartis Investigative Site
Brussels, 1200
Novartis Investigative Site
Ghent, 9000
Novartis Investigative Site
Laken, 1020
Novartis Investigative Site
Leuven, 3000
Brazil4 sites
Novartis Investigative Site
Curitiba, Paraná, 80060-900
Novartis Investigative Site
Rio de Janeiro, Rio de Janeiro, 20551-030
Novartis Investigative Site
Rio de Janeiro, Rio de Janeiro, 21941-912
Novartis Investigative Site
São Paulo, São Paulo, 04023-900
France4 sites
Novartis Investigative Site
Le Kremlin-Bicêtre, 94275
Novartis Investigative Site
Lyon, 69677
Novartis Investigative Site
Paris, 75015
Novartis Investigative Site
Strasbourg, 67098
Spain4 sites
Novartis Investigative Site
Esplugues de Llobregat, Barcelona, 08950
Novartis Investigative Site
Madrid, 28009
Novartis Investigative Site
Madrid, 28034
Novartis Investigative Site
Valencia, Valencia, 46026
Turkey (Türkiye)4 sites
Novartis Investigative Site
Ankara, 06100
Novartis Investigative Site
Balcova / Izmir, 35340
Novartis Investigative Site
Fatih / Istanbul, 34098
Novartis Investigative Site
Istanbul, 34722
Canada3 sites
Novartis Investigative Site
Montreal, Quebec, H3T 1C5
Novartis Investigative Site
Toronto, Ontario, M5G 1X8
Novartis Investigative Site
Vancouver, British Columbia
Greece3 sites
Novartis Investigative Site
Ampelokipoi, GR, 115 27
Novartis Investigative Site
Goudi- Athens, 115 27
Novartis Investigative Site
Thessaloniki, GR, 546 39
Russia3 sites
Novartis Investigative Site
Moscow, 115522
Novartis Investigative Site
Moscow, 119991
Novartis Investigative Site
Saint Petersburg, 194100
About this study
Official title: An Open-label Extension Study of Canakinumab (ACZ885) in Patients With Systemic Juvenile Idiopathic Arthritis (SJIA) and Active Systemic Manifestations Who Participated in Studies ACZ885G2301 and ACZ885G2305; and Response Characterization Study in Canakinumab Treatment-naïve Patients With Active SJIA With and Without Fever
This open-label extension study will permit patients with Systemic Juvenile Idiopathic Arthritis (SJIA) who previously were responsive to treatment with canakinumab and canakinumab treatment-naïve patients with active SJIA with and without fever to be retreated with 4 mg/kg s.c. every 4 weeks and assessed for continued efficacy and safety until discontinuation or when study CACZ885G2402 is in place at their study center or around March 2013, whichever occurs first. Patients who are steroid-free will be able to taper their canakinumab dose to 2 mg/kg s.c. every 4 weeks.
- Conditions
- Systemic Juvenile Idiopathic Arthritis
- Being tested
- Canakinumab
- Keywords
- Flare, arthritis, IL-1beta antagonist, systemic juvenile idiopathic arthritis, CHAQ, steroids, ACR pediatric response, Systemic juvenile idiopathic arthritis with active flare
- Medical subject headings
- Arthritis, Juvenile, Arthritis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CanakinumabDrug
Canakinumab
| Study group | Role | What they receive |
|---|---|---|
| Canakinumab | Experimental | Canakinumab Receives: Drug: Canakinumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), AEs by Severity, AEs Leading to Discontinuation, SAEs Leading to Discontinuation, Treatment Related AEs and SAE
An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not related to study drug. A SAE was defined as an event which was fatal or life threatening, required or prolonged hospitalization, was significantly or permanently disabling or incapacitating, constituted a congenital anomaly or a birth defect, or encompassed any other clinically significant event that could jeopardize the participants or require medical or surgical intervention to prevent one of the aforementioned outcomes. Treatment related AEs or SAEs were defined as AEs or SAEs that were suspected to be related to study treatment as per investigator.
Measured: From start of study treatment (Day 1) up to end of follow-up period (Week 271 for ACZ885 treated participants and Week 145 for ACZ885 treatment naive participants)
Number of Participants With Anti -ACZ885 Antibodies at Any Visit During the Study
Immunogenicity assessment included determination of anti-canakinumab (ACZ885) antibodies in serum samples using BIAcore system.
Measured: From start of study treatment (Day 1) up to end of follow-up period (Week 271 for ACZ885 treated participants and Week 145 for ACZ885 treatment naive participants)
Number of Participants With Clinically Significant Local Injection Site Reactions During the Study
Local injection site tolerability was assessed on the injection site. Each participant was classified into one of the following four categories: 1. no tolerability reactions at any time during the study, 2. mild reaction observed on at least one occasion but no moderate or severe reactions. 3. moderate reaction observed on at least one occasion but no severe reaction. 4. severe reaction observed on at least one occasion.
Measured: From start of study treatment (Day 1) up to end of follow-up period (Week 271 for ACZ885 treated participants and Week 145 for ACZ885 treatment naive participants)
Percentage of Participants Previously Treated With Anakinra Who Achieved Minimum Response of American College of Rheumatology (ACR) Pediatric 30/50/70/90/100 at Last Assessment of Study
Adapted ACR Paediatric 30/50/70/90 or 100 was assessed based on following 7 variables: 1.Physician's Global Assessment on a 1-100 millimeter (mm) visual analog scale (VAS); 2. Participants Global Assessment on a 1-100 mm VAS; 3. Functional ability; 4. Joints count with active arthritis; 5. Joints count with limitation of motion; 6. Laboratory measure of C-reactive protein (CRP) and 7. Absence of intermittent fever due to severe juvenile idiopathic arthritis (SJIA) during the preceding week. Response was defined as more than or equal to (≥) 30%/50%/70%/90% or 100% improvement in at least 3 of the response variables 1 to 6, no intermittent fever (i.e. body temperature less than or equal to (≤) 38 °C) in the preceding week (variable 7) and with no more than one variable 1 to 6, worsening by more than 30%.
Measured: Baseline up to last assessment (4 years) or date of discontinuation, which ever occurred earlier
Percentage of Participants Previously Treated With Tocilizumab Who Achieved Minimum Response of American College of Rheumatology (ACR) Pediatric 30/50/70/90/100 at Last Assessment of Study
Adapted ACR Paediatric 30/50/70/90 or 100 was assessed based on following 7 variables: 1.Physician's Global Assessment on a 0-100 mm VAS; 2. Participants Global Assessment on a 0-100 mm VAS; 3. Functional ability; 4. Joints count with active arthritis; 5. Joints count with limitation of motion; 6. Laboratory measure of CRP and 7. Absence of intermittent fever due to SJIA during the preceding week. Response was defined as ≥ 30%/50%/70%/90% or 100% improvement in at least 3 of the response variables 1 to 6, no intermittent fever (i.e. body temperature ≤ 38 °C) in the preceding week (variable 7) and with no more than one variable 1 to 6, worsening by more than 30%.
Measured: Baseline up to last assessment (4 years) or date of discontinuation, which ever occurred earlier
Percentage of Participants Previously Treated With Other Biologics Who Achieved Minimum Response of American College of Rheumatology (ACR) Pediatric 30/50/70/90/100 at Last Assessment of Study
Adapted ACR Paediatric 30/50/70/90 or 100 was assessed based on following 7 variables: 1.Physician's Global Assessment on a 0-100 mm VAS; 2. Participants Global Assessment on a 0-100 mm VAS; 3. Functional ability; 4. Joints count with active arthritis; 5. Joints count with limitation of motion; 6. Laboratory measure of CRP and 7. Absence of intermittent fever due to SJIA during the preceding week. Response was defined as ≥ 30%/50%/70%/90% or 100% improvement in at least 3 of the response variables 1 to 6, no intermittent fever (i.e. body temperature ≤ 38 °C) in the preceding week (variable 7) and with no more than one variable 1 to 6, worsening by more than 30%.
Measured: Baseline up to last assessment (4 years) or date of discontinuation, which ever occurred earlier
Secondary outcomes (13)
Percentage of Non--Responders Who Achieved Minimum Response of American College of Rheumatology (ACR) Pediatric 30/50/70/90/100
Adapted ACR Paediatric 30/50/70/90 or 100 was assessed based on following 7 variables: 1.Physician's Global Assessment on a 0-100 mm VAS; 2. Participants Global Assessment on a 0-100 mm VAS; 3. Functional ability; 4. Joints count with active arthritis; 5. Joints count with limitation of motion; 6. Laboratory measure of -CRP and 7. Absence of intermittent fever due to SJIA during the preceding week. Response was defined as ≥ 30%/50%/70%/90% or 100% improvement in at least 3 of the response variables 1 to 6, no intermittent fever (i.e. body temperature ≤ 38°C) in the preceding week (variable 7) and with no more than one variable 1 to 6, worsening by more than 30%.
Measured: Baseline up to last assessment (4 years) or date of discontinuation, which ever occurred earlier
Percentage of Participants With Minimum Adapted ACR Pediatric ≥ 30 at Baseline Who Achieved Minimum Response of ACR Pediatric 30/50/70/90/100 at Last Assessment of Study
Adapted ACR Paediatric 30/50/70/90 or 100 was assessed based on following 7 variables: 1.Physician's Global Assessment on a 0-100 mm VAS; 2. Participants Global Assessment on a 0-100 mm VAS; 3. Functional ability; 4. Joints count with active arthritis; 5. Joints count with limitation of motion; 6. Laboratory measure of CRP and 7. Absence of intermittent fever due to SJIA during the preceding week. Response was defined as ≥ 30%/50%/70%/90% or 100% improvement in at least 3 of the response variables 1 to 6, no intermittent fever in the preceding week (variable 7) and with no more than one variable 1 to 6 worsening by more than 30%. For minimum adapted ACR paediatric scores, the last measurement recorded from the participant's previous study was considered baseline for the current study.
Measured: Baseline up to last assessment (4 years) or date of discontinuation, which ever occurred earlier
Percentage of Participants Able to Taper Oral Steroid Use or Reached Steroid Free Regimen
Steroid tapering with oral steroids was allowed if the participant achieved an adapted ACR Paediatric 50 response and had no fever. A participant was considered to have tapered steroids successfully, if the steroid dose was reduced from baseline and the participant did not flare and maintained a minimum adapted ACR Paediatric 30 at the last measurement. A participant was considered to have unsuccessfully tapered steroids if the steroid dose was reduced during the study but dose at last assessment was equal to or greater than dose at baseline or; if steroid dose was reduced but the participant did not maintain a minimum adapted ACR Paediatric 30 at the last measurement.
Measured: Baseline up to last assessment (4 years) or date of discontinuation, which ever occurred earlier
Number of Participants Who Reduced Their Canakinumab Dose to 2 mg/kg
The canakinumab dose could be reduced from 4 mg/kg to 2 mg/kg in participants who were steroid-free, if requested by the treating physician and agreed by the sponsor. For treatment naive participants , dose reduction was allowed after the participant had received 6 months treatment with canakinumab.
Measured: Baseline up to last assessment (4 years) or date of discontinuation, which ever occurred earlier
Percentage of Participants With Clinical Remission
Clinical remission was defined as at least 6 months of inactive disease or at least 12 months of inactive disease on medication during the extension period. Participants with inactive disease for at least 6 months, but had loss of inactive disease before 12 months were also determined.
Measured: Baseline up to last assessment (4 years) or date of discontinuation, which ever occurred earlier
Change From Baseline in Disability, Overall Well-Being and Pain Intensity Scores Based on Child Health Assessment Questionnaire (CHAQ) to Last Assessment of Study
The CHAQ was used to assess physical ability, overall well- being and pain intensity experienced by participants. The CHAQ (disability and well-being) dimension consisted 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". Participants were graded for the response in four categories, ranging from 0 (without any difficulty), 1 (with some difficulty), 2 (with much difficulty) and 3 (unable to do). Participant's pain intensity was assessed by parents and adult participants (18-20 years old) on a VAS scale of 0-100 mm (0 mm: no pain to 100: very severe pain). Change from baseline was calculated by using the formula = (post baseline value - baseline value). For both scales, lower scores indicate increased functional ability.
Measured: Baseline up to last assessment (4 years) or date of discontinuation, which ever occurred earlier
Change From Baseline in Health-Related Quality of Life (HRQoL) Over Time Based on Child Health Questionnaire- Parent Form (CHQ-PF50) to Last Assessment of Study
The Child Health Questionnaire - Parent Form (CHQ-PF50) instrument was used to measure HRQoL aged 5 to 18 years from a parent's perspective. This 14 concept questionnaire measured physical and psychosocial health of the participants on following points: 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. Total score ranged from 1-100. Increase in score represented improvement in overall well being of participants. Change from baseline was calculated by using the formula = (post baseline value - baseline value).
Measured: Baseline up to last assessment (4 years) or date of discontinuation, which ever occurred earlier
Change From Baseline in EuroQual 5 -Dimension Health Status Questionnaire (EQ-5D) Utility Index and Health State Assessment Scores [EQ Visual Analog Scale (EQ-VAS)] to Last Assessment of Study
EQ-5D HRQoL tool was used for participants above 12 years and EQ-5D proxy for 8-11 years. EQ-5D index scores range from -0.11 (worst possible health, worse than dead), to 0 (dead) to 1 (perfect health). Utility based EQ-5D questionnaire provides generic measure of health for clinical and economic appraisal based on 2 parts: EQ-5D descriptive system - 5 dimensions each with 3 levels (1:no, 2:moderate, 3:severe problem) on: mobility (1=0, 2=0.069, 3=0.314), self-care (1=0, 2=0.104, 3=0.214), usual activities (1=0, 2=0.036, 3=0.094), pain/discomfort (1=0, 2=0, 3=0.386) and anxiety/depression (1=0, 2=0.071, 3=0.2). EQ-5D Total score= 1-0.081-(score of level 2 in present)-0.269 (if at least one of level 3 presents). EQ-5D total score: 1=high quality of life; -0.59 worst quality of life; and EQ-VAS - record participant's self-rated health on vertical, visual analog scale as '100=Best and 0=Worst imaginable health state'.
Positive change from baseline score indicated improved health status.
Measured: Baseline up to last assessment (4 years) or date of discontinuation, which ever occurred earlier
Change From Baseline in Pediatric Daytime Sleepiness Scale (PDSS) Score to Last Assessment of Study
Sleep patterns in children and adolescents aged between 11 and 15 years were determined using PDSS instrument to evaluate whether canakinumab helps in reducing sleepiness in children with SJIA. Participants were assessed on 8 items of PDSS, on a scale of 0 to 4 (0 - never, 1 - seldom, 2- sometimes, 3 - frequently and 4 - always). The sum of all the items was reported as total score with a range of 0-32. Change from baseline was calculated by using the formula = (post baseline value - baseline value). A positive change from baseline score indicated improvement.
Measured: Baseline up to last assessment (4 years) or date of discontinuation, which ever occurred earlier
Change From Baseline in Growth Velocity Parameter for Height to Last Assessment of Study
Growth velocity parameter height percentile was determined. Percentile was based on the growth charts smoothed percentile curve released by Centers for Disease control and prevention (CDC) in 2000, by sex and age.
Measured: Baseline up to last assessment (4 years) or date of discontinuation, which ever occurred earlier
Percentage of Participants With Inactive Disease
Inactive disease was defined as no joints with active arthritis; no fever (body temperature ≤ 38 degree Celsius); no rheumatoid rash, serositis, splenomegaly, hepatomegaly, or generalized lymphadenopathy attributable to SJIA; normal CRP, and a rating of no disease activity on the Physician's Global Assessment of disease activity (with a best possible score ≤10 mm on the VAS).
Measured: Baseline up to last assessment (4 years) or date of discontinuation, which ever occurred earlier
Change From Baseline in Growth Velocity Parameters to Last Assessment of Study
Growth velocity parameter weight percentile was determined. Percentile was based on the growth charts smoothed percentile curve released by Centers for Disease control and prevention (CDC) in 2000, by sex and age.
Measured: Baseline up to last assessment (4 years) or date of discontinuation, which ever occurred earlier
Change From Baseline in Growth Velocity Parameter for BMI to Last Assessment of Study
Growth velocity parameter BMI percentile was determined. Percentile was based on the growth charts smoothed percentile curve released by Centers for Disease control and prevention (CDC) in 2000, by sex and age.
Measured: Baseline up to last assessment (4 years) or date of discontinuation, which ever occurred earlier
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Apr 2009 (estimated)
- Study startSep 2009
- Primary completionDec 2014
- Study completionDec 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Systemic Juvenile Idiopathic ArthritisStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 270 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Pediatric Rheumatology International Trials Organization
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00891046
- Sponsor's protocol ID
- CACZ885G2301E1
- Other IDs
- EudraCT: 2008-008008-42
- Acronym
- β-SPECIFIC 3
- Status last verified
- Jul 2018
- First submitted
- 29 Apr 2009
- Last updated
- 26 Mar 2019
- Results posted
- Yes, on ClinicalTrials.gov
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 30269054Grom 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
Study at a glance
From the registry record, last updated by the sponsor on 26 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label Extension Study of Canakinumab (ACZ885) in Patients With Systemic Juvenile Idiopathic Arthritis (SJIA) and Active Systemic Manifestations Who Participated in Studies ACZ885G2301 and ACZ885G2305; and Response Characterization Study in Canakinumab Treatment-naïve Patients With Active SJIA With and Without Fever
- ClinicalTrials.gov ID
- NCT00891046
- Acronym / sponsor ID
- β-SPECIFIC 3 / CACZ885G2301E1
- Conditions
- Systemic Juvenile Idiopathic Arthritis
- Keywords
- Flare, arthritis, IL-1beta antagonist, systemic juvenile idiopathic arthritis, CHAQ, steroids, ACR pediatric response, Systemic juvenile idiopathic arthritis with active flare
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 270 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Collaborators
- Pediatric Rheumatology International Trials Organization
- Study start
- Sep 2009
- Primary completion
- Dec 2014 (actual)
- Study completion
- Dec 2014 (actual)
- First posted
- 30 Apr 2009 (estimated)
- Results
- Posted 10 Mar 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This open-label extension study will permit patients with Systemic Juvenile Idiopathic Arthritis (SJIA) who previously were responsive to treatment with canakinumab and canakinumab treatment-naïve patients with active SJIA with and without fever to be retreated with 4 mg/kg s.c. every 4 weeks and assessed for continued efficacy and safety until discontinuation or when study CACZ885G2402 is in place at their study center or around March 2013, whichever occurs first. Patients who are steroid-free will be able to taper their canakinumab dose to 2 mg/kg s.c. every 4 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Canakinumab | Experimental | Drug: CanakinumabCanakinumab |
Who may qualify
- Ages
- 2 to 19 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (10 listed)
- Patients from study CACZ885G2305 or CACZ885G2301 who achieved an adapted ACR pediatric 30 response 15 days after their initial dose of canakinumab but clinically deteriorated afterwards or a minimum ACR Pediatric 30 response was not maintained after Day 15 and intervention is deemed necessary by the investigator, or Patients in study CACZ885G2301 who are not eligible to enter Part II (withdrawal part) because they were not able to meet the corticosteroid entry criteria , or Responder patients in Part I or Part II who had not flared when CACZ885G2301 was stopped, or CACZ885G2301 patients who were responders in Part I but experienced a flare in Part II.
- Treatment-naïve patients need to meet the following criteria:
- Other protocol-defined inclusion criteria may apply
Key exclusion criteria (3 listed)
- History of allergy or hypersensitivity to study drug
- With active or recurrent bacterial, fungal or viral infections at time of enrollment
- Other protocol inclusion/exclusion criteria may apply
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CanakinumabCanakinumab | Drug | Canakinumab |
Primary outcome
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), AEs by Severity, AEs Leading to Discontinuation, SAEs Leading to Discontinuation, Treatment Related AEs and SAE
Time frame: From start of study treatment (Day 1) up to end of follow-up period (Week 271 for ACZ885 treated participants and Week 145 for ACZ885 treatment naive participants)
An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not related to study drug. A SAE was defined as an event which was fatal or life threatening, required or prolonged hospitalization, was significantly or permanently disabling or incapacitating, constituted a congenital anomaly or a birth defect, or encompassed any other clinically significant event that could jeopardize the participants or require medical or surgical intervention to prevent one of the aforementioned outcomes. Treatment related AEs or SAEs were defined as AEs or SAEs that were suspected to be related to study treatment as per investigator.
Number of Participants With Anti -ACZ885 Antibodies at Any Visit During the Study
Time frame: From start of study treatment (Day 1) up to end of follow-up period (Week 271 for ACZ885 treated participants and Week 145 for ACZ885 treatment naive participants)
Immunogenicity assessment included determination of anti-canakinumab (ACZ885) antibodies in serum samples using BIAcore system.
Number of Participants With Clinically Significant Local Injection Site Reactions During the Study
Time frame: From start of study treatment (Day 1) up to end of follow-up period (Week 271 for ACZ885 treated participants and Week 145 for ACZ885 treatment naive participants)
Local injection site tolerability was assessed on the injection site. Each participant was classified into one of the following four categories: 1. no tolerability reactions at any time during the study, 2. mild reaction observed on at least one occasion but no moderate or severe reactions. 3. moderate reaction observed on at least one occasion but no severe reaction. 4. severe reaction observed on at least one occasion.
Percentage of Participants Previously Treated With Anakinra Who Achieved Minimum Response of American College of Rheumatology (ACR) Pediatric 30/50/70/90/100 at Last Assessment of Study
Time frame: Baseline up to last assessment (4 years) or date of discontinuation, which ever occurred earlier
Adapted ACR Paediatric 30/50/70/90 or 100 was assessed based on following 7 variables: 1.Physician's Global Assessment on a 1-100 millimeter (mm) visual analog scale (VAS); 2. Participants Global Assessment on a 1-100 mm VAS; 3. Functional ability; 4. Joints count with active arthritis; 5. Joints count with limitation of motion; 6. Laboratory measure of C-reactive protein (CRP) and 7. Absence of intermittent fever due to severe juvenile idiopathic arthritis (SJIA) during the preceding week. Response was defined as more than or equal to (≥) 30%/50%/70%/90% or 100% improvement in at least 3 of the response variables 1 to 6, no intermittent fever (i.e. body temperature less than or equal to (≤) 38 °C) in the preceding week (variable 7) and with no more than one variable 1 to 6, worsening by more than 30%.
Percentage of Participants Previously Treated With Tocilizumab Who Achieved Minimum Response of American College of Rheumatology (ACR) Pediatric 30/50/70/90/100 at Last Assessment of Study
Time frame: Baseline up to last assessment (4 years) or date of discontinuation, which ever occurred earlier
Adapted ACR Paediatric 30/50/70/90 or 100 was assessed based on following 7 variables: 1.Physician's Global Assessment on a 0-100 mm VAS; 2. Participants Global Assessment on a 0-100 mm VAS; 3. Functional ability; 4. Joints count with active arthritis; 5. Joints count with limitation of motion; 6. Laboratory measure of CRP and 7. Absence of intermittent fever due to SJIA during the preceding week. Response was defined as ≥ 30%/50%/70%/90% or 100% improvement in at least 3 of the response variables 1 to 6, no intermittent fever (i.e. body temperature ≤ 38 °C) in the preceding week (variable 7) and with no more than one variable 1 to 6, worsening by more than 30%.
Percentage of Participants Previously Treated With Other Biologics Who Achieved Minimum Response of American College of Rheumatology (ACR) Pediatric 30/50/70/90/100 at Last Assessment of Study
Time frame: Baseline up to last assessment (4 years) or date of discontinuation, which ever occurred earlier
Adapted ACR Paediatric 30/50/70/90 or 100 was assessed based on following 7 variables: 1.Physician's Global Assessment on a 0-100 mm VAS; 2. Participants Global Assessment on a 0-100 mm VAS; 3. Functional ability; 4. Joints count with active arthritis; 5. Joints count with limitation of motion; 6. Laboratory measure of CRP and 7. Absence of intermittent fever due to SJIA during the preceding week. Response was defined as ≥ 30%/50%/70%/90% or 100% improvement in at least 3 of the response variables 1 to 6, no intermittent fever (i.e. body temperature ≤ 38 °C) in the preceding week (variable 7) and with no more than one variable 1 to 6, worsening by more than 30%.
13 secondary outcomes
Percentage of Non--Responders Who Achieved Minimum Response of American College of Rheumatology (ACR) Pediatric 30/50/70/90/100
Time frame: Baseline up to last assessment (4 years) or date of discontinuation, which ever occurred earlier
Percentage of Participants With Minimum Adapted ACR Pediatric ≥ 30 at Baseline Who Achieved Minimum Response of ACR Pediatric 30/50/70/90/100 at Last Assessment of Study
Time frame: Baseline up to last assessment (4 years) or date of discontinuation, which ever occurred earlier
Percentage of Participants Able to Taper Oral Steroid Use or Reached Steroid Free Regimen
Time frame: Baseline up to last assessment (4 years) or date of discontinuation, which ever occurred earlier
Number of Participants Who Reduced Their Canakinumab Dose to 2 mg/kg
Time frame: Baseline up to last assessment (4 years) or date of discontinuation, which ever occurred earlier
Percentage of Participants With Clinical Remission
Time frame: Baseline up to last assessment (4 years) or date of discontinuation, which ever occurred earlier
Change From Baseline in Disability, Overall Well-Being and Pain Intensity Scores Based on Child Health Assessment Questionnaire (CHAQ) to Last Assessment of Study
Time frame: Baseline up to last assessment (4 years) or date of discontinuation, which ever occurred earlier
Change From Baseline in Health-Related Quality of Life (HRQoL) Over Time Based on Child Health Questionnaire- Parent Form (CHQ-PF50) to Last Assessment of Study
Time frame: Baseline up to last assessment (4 years) or date of discontinuation, which ever occurred earlier
Change From Baseline in EuroQual 5 -Dimension Health Status Questionnaire (EQ-5D) Utility Index and Health State Assessment Scores [EQ Visual Analog Scale (EQ-VAS)] to Last Assessment of Study
Time frame: Baseline up to last assessment (4 years) or date of discontinuation, which ever occurred earlier
Change From Baseline in Pediatric Daytime Sleepiness Scale (PDSS) Score to Last Assessment of Study
Time frame: Baseline up to last assessment (4 years) or date of discontinuation, which ever occurred earlier
Change From Baseline in Growth Velocity Parameter for Height to Last Assessment of Study
Time frame: Baseline up to last assessment (4 years) or date of discontinuation, which ever occurred earlier
Percentage of Participants With Inactive Disease
Time frame: Baseline up to last assessment (4 years) or date of discontinuation, which ever occurred earlier
Change From Baseline in Growth Velocity Parameters to Last Assessment of Study
Time frame: Baseline up to last assessment (4 years) or date of discontinuation, which ever occurred earlier
Change From Baseline in Growth Velocity Parameter for BMI to Last Assessment of Study
Time frame: Baseline up to last assessment (4 years) or date of discontinuation, which ever occurred earlier
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Mar 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 30269054Ruperto 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.
- Derived from this study: PubMed 26314396Grom 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.
- Related InfoLink provided by the sponsor.
- Related InfoLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
73 sites in 21 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Canakinumab in people with Systemic Juvenile Idiopathic Arthritis, run by Novartis Pharmaceuticals at 73 sites in 21 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 3 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 26 Mar 2019. 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 Germany, United Kingdom, United States, Israel, Italy and 16 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. 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 10 Mar 2017). 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?
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), AEs by Severity, AEs Leading to Discontinuation, SAEs Leading to Discontinuation, Treatment Related AEs and SAE (time frame: From start of study treatment (Day 1) up to end of follow-up period (Week 271 for ACZ885 treated participants and Week 145 for ACZ885 treatment naive participants)). The study lists 6 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 NCT00891046, which also lists 2 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 26 Mar 2019; AzTrials last refreshed its copy on 7 Nov 2026.