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.

NCT00891046 | Completed Phase 3 Results

• 2 other identifiers: CACZ885G2301E1EudraCT: 2008-008008-42
• Study Type: interventional
• Target: 270
• Locations: 21 countries
• Sites: 73

Brief 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. 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

Keywords

Flare; arthritis; IL-1beta antagonist; systemic juvenile idiopathic arthritis; CHAQ; steroids; ACR pediatric response; Systemic juvenile idiopathic arthritis with active flare

Outcome Measures

Primary Outcomes (6)

• 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.

  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.

  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.

  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%.

  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%.

  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%.

  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

  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

  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

  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

  Baseline up to last assessment (4 years) or date of discontinuation, which ever occurred earlier

• Percentage of Participants With Clinical Remission

  Baseline up to last assessment (4 years) or date of discontinuation, which ever occurred earlier

Study Arms (1)

Canakinumab

EXPERIMENTAL

Canakinumab

Drug: Canakinumab

Interventions

Canakinumab DRUG

Canakinumab

Canakinumab

Eligibility Criteria

• Age: 2 Years - 19 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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
• 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

You may not qualify if:

• History of allergy or hypersensitivity to study drug
• With active or recurrent bacterial, fungal or viral infections at time of enrollment

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead
• Pediatric Rheumatology International Trials Organization: collaborator

Study Sites (73)

Novartis Investigative Site

Los Angeles, California, 90027, United States

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Novartis Investigative Site

Louisville, Kentucky, 40202, United States

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Boston, Massachusetts, 02111, United States

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Cincinnati, Ohio, 45229, United States

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Columbus, Ohio, 43205, United States

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Portland, Oregon, 97232, United States

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CABA, Buenos Aires, C1270AAN, Argentina

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Vienna, A-1090, Austria

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Brussels, 1200, Belgium

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Ghent, 9000, Belgium

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Laken, 1020, Belgium

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Leuven, 3000, Belgium

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Curitiba, Paraná, 80060-900, Brazil

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Rio de Janeiro, Rio de Janeiro, 20551-030, Brazil

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Rio de Janeiro, Rio de Janeiro, 21941-912, Brazil

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São Paulo, São Paulo, 04023-900, Brazil

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Vancouver, British Columbia, Canada

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Toronto, Ontario, M5G 1X8, Canada

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Montreal, Quebec, H3T 1C5, Canada

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Le Kremlin-Bicêtre, 94275, France

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Lyon, 69677, France

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Paris, 75015, France

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Strasbourg, 67098, France

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Bad Bramstedt, 24576, Germany

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Berlin, 13125, Germany

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Berlin, 13353, Germany

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Freiburg im Breisgau, 79106, Germany

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Garmisch-Partenkirchen, 82467, Germany

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Giessen, 35392, Germany

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Hamburg, 20246, Germany

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Hamburg, 22081, Germany

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Hanover, 30625, Germany

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Heidelberg, 69120, Germany

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Münster, 48149, Germany

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Saint Augustin, 53757, Germany

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Tübingen, 72076, Germany

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Ampelokipoi, GR, 115 27, Greece

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Thessaloniki, GR, 546 39, Greece

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Goudi- Athens, 115 27, Greece

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Budapest, 1094, Hungary

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Haifa, 31096, Israel

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Kfar Saba, 4428164, Israel

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Petah Tikva, 49202, Israel

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Ramat Gan, 5266202, Israel

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Rehovot, 76100, Israel

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Florence, FI, 50132, Italy

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Genova, GE, 16147, Italy

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Milan, MI, 20100, Italy

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Milan, MI, 20122, Italy

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Napoli, 80131, Italy

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Utrecht, 3584 EA, Netherlands

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Novartis Investigative Site

Breña, Lima region, 05, Peru

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Novartis Investigative Site

Warsaw, 02-637, Poland

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Moscow, 115522, Russia

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Moscow, 119991, Russia

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Saint Petersburg, 194100, Russia

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Novartis Investigative Site

Esplugues de Llobregat, Barcelona, 08950, Spain

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Valencia, Valencia, 46026, Spain

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Madrid, 28009, Spain

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Madrid, 28034, Spain

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Stockholm, 171 76, Sweden

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Lausanne, 1011, Switzerland

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Ankara, 06100, Turkey (Türkiye)

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Balcova / Izmir, 35340, Turkey (Türkiye)

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Fatih / Istanbul, 34098, Turkey (Türkiye)

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Istanbul, 34722, Turkey (Türkiye)

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Bath, BS2 8BJ, United Kingdom

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Birmingham, B4 6NH, United Kingdom

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Liverpool, L12 2AP, United Kingdom

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London, WC1N 1EH, United Kingdom

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Manchester, M9 2AA, United Kingdom

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Newcastle Upon Tyme, NE4 4LP, United Kingdom

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Novartis Investigative Site

Oxford, OX3 7LD, United Kingdom

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Related Publications (2)

• 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.

  PMID: 30269054 DERIVED

• 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.

  PMID: 26314396 DERIVED

Related Links

• Related Info
• Related Info

MeSH Terms

Conditions

Arthritis, Juvenile; Arthritis

Interventions

canakinumab

Condition Hierarchy (Ancestors)

Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862--778--8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 29, 2009
• First Posted: April 30, 2009
• Study Start: September 1, 2009
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: March 26, 2019
• Results First Posted: March 10, 2017

Record last verified: 2018-07

Locations

SE (1); DE (13); ES (4); IL (5); PL (1); BR (4); US (6); CH (1); GB (7); GR (3); IT (5); TU (4); CA (3); RU (3); FR (4); BE (4); AU (1); HU (1); AR (1); NL (1); PE (1)