Single-dose Study to Assess Efficacy of Canakinumab (ACZ885) in Patients With Active Juvenile Idiopathic Arthritis (SJIA)

NCT00886769 | Terminated Phase 3 Results

• 2 other identifiers: CACZ885G2305EudraCT: 2008-005476-27
• Study Type: interventional
• Target: 84
• Locations: 22 countries
• Sites: 91

Brief Summary

This study assessed the initial efficacy and safety of canakinumab over a 4 week period in patients with systemic juvenile idiopathic arthritis (SJIA) having a flare. Response to treatment will be according to the adapted American College of Rheumatology(ACR)Pediatric 30 criteria at Day 15.

Conditions

Systemic Juvenile Idiopathic Arthritis

Keywords

Flare; arthritis; IL-1beta antagonist; systemic juvenile idiopathic arthritis; Juvenile Rheumatoid; Systemic juvenile idiopathic arthritis with active flare

Outcome Measures

Primary Outcomes (1)

• Percentage of Patients Who Meet the Adapted American College of Rheumatology (ACR) Pediatric 30 Criteria

  Adapted ACR Pediatric 30 criteria determined responders (improved from baseline of at least 30% in at least 3 response variables 1-6 and no intermittent fever in preceding week \[variable 7\], with no more than one variable 1-6 worsening \> 30% ) 1. Physician's Global Assessment of disease activity: 0-100 mm VAS 2.Parent/Patient's Global Assessment of Patient's overall wellbeing: 0-100mmVAS in Child Health Assessment Questionnaire (CHAQ) 3. Functional ability: CHAQ 4.Number of joints with active arthritis 5. Number of joints with limited of motion 6. Laboratory measure of inflammation CRP (mg/L)

  Baseline, Day 15, Day 29

Secondary Outcomes (9)

• Percentage of Patients Achieving the Adapted ACR Pediatric 50 Criteria

  Baseline, Day 15, Day 29

• Percentage of Patients Achieving the Adapted ACR Pediatric 70

  Baseline, Day 15, Day 29

• Percentage of Patients Achieving the Adapted ACR Pediatric 90

  Baseline, Day 15, Day 29

• Percentage of Patients Achieving the Adapted ACR Pediatric 100

  baseline, Day 15, Day 29

• Change in Patient's Pain Intensity as Assessed on a 100-mm Visual Analog Scale (VAS)as Part of the Childhood Health Assessment Questionnaire(CHAQ)

  Baseline, Day 15

Study Arms (2)

Canakinumab

EXPERIMENTAL

Patients received a single dose of subcutaneous(sc) injection of canakinumab (4 mg/kg) on Day 1. Maximal total single dose of canakinumab allowed was 300 mg. Any patient who required a dose greater than 150 mg (patients\>37.5 kg) received two sc injections.

Drug: Canakinumab

Placebo

PLACEBO COMPARATOR

Patients received a single dose matching placebo of canakinumab on day 1.

Drug: Placebo

Interventions

Canakinumab DRUG

Canakinumab was supplied in individual 6 mL glass vials each containing 150 mg canakinumab powder as a lyophilized cake. Each reconstituted vial provided 150mg of canakinumab per 1 mL.

Also known as: ACZ885

Canakinumab

Placebo DRUG

Placebo was provided in individual 6 mL glass vials each containing 150 mg placebo powder matching canakinumab as a lyophilized cake. Each reconstitued vial provided 150mg of placebo per 1 mL.

Placebo

Eligibility Criteria

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

You may qualify if:

• 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:
• Arthritis in one or more joints with or preceded by fever of at least 2 weeks duration that is documented to be daily/quotidian for at least 3 days and accompanied by one or more of the following:
• evanescent nonfixed erythematous rash,
• generalized lymph node enlargement,
• hepatomegaly and/ or splenomegaly,
• serositis
• Parent's or legal guardian's written informed consent and child's assent, if appropriate, or patient's informed consent for ≥ 18 years of age
• Male and female patients aged ≥ 2 to \< 20 years of age
• Active disease at the time of enrollment defined as follows:
• At least 2 joints with active arthritis
• Documented spiking, intermittent fever (body temperature \> 38°C) for at least 1 day during the screening period within 1 week before first canakinumab/placebo dose
• C-reactive protein (CRP) \> 30 mg/L (normal range \< 10 mg/L)
• Naïve to canakinumab

You may not qualify if:

• Pregnant or nursing (lactating) female patients
• Female patients having reached sexual maturity unless their career, lifestyle, or sexual orientation precluded intercourse with a male partner and/or they were using an acceptable method of contraception
• History of hypersensitivity to study drug or to biologics.
• Diagnosis of active macrophage-activation syndrome (MAS) (Ravelli, Magni-Manzoni and Pistorio 2005) within the last 6 months
• With active or recurrent bacterial, fungal or viral infection, including patients with evidence of human immunodeficiency virus (HIV) infection, hepatitis B or hepatitis C infection

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead
• International Maternal Pediatric Adolescent AIDS Clinical Trials Group: collaborator
• Southwest Pediatric Nephrology Study Group: collaborator

Study Sites (91)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

Arkansas Children's Hospital Research Inst

Little Rock, Arkansas, 72202, United States

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Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

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Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

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University of Chicago Medical Center

Chicago, Illinois, 60637, United States

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University of Louisville

Louisville, Kentucky, 40202, United States

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Tufts Medical Center

Boston, Massachusetts, 02111, United States

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Tufts New England Medical Center-Dept. of Allergy

Boston, Massachusetts, 02111, United States

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St. Barnabas Ambulatory Care Center

Livingston, New Jersey, 07039, United States

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Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

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Children's Hospital/Neurology

Cinncinati, Ohio, 45229, United States

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Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

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Legacy Emanuel Hospital

Portland, Oregon, 97227, United States

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Legacy Emanual Research

Portland, Oregon, 97232, United States

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Specially For Children

Austin, Texas, 78723, United States

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Novartis Investigative Site

Buenos Aires, Argentina

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Capital Federal, Argentina

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La Plata, Argentina

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Brussels, Belgium

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Ghent, Belgium

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Laken, Belgium

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Leuven, Belgium

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Curitiba, Brazil

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Porto Alegre, Brazil

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Rio de Janeiro, Brazil

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São Paulo, Brazil

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Vancouver, British Columbia, Canada

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Halifax, Nova Scotia, Canada

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Toronto, Ontario, Canada

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Montreal, Quebec, Canada

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Calgary, Canada

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Arhus N, Denmark

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Le Kremlin-Bicêtre, France

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Lyon, France

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Paris, France

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Strasbourg, France

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Bad Bamstedt, Germany

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Berlin, Germany

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Bremen, Germany

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Dresden, Germany

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Freiburg im Breisgau, Germany

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Garmisch-Partenkirch, Germany

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Geißen, Germany

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Hamburg, Germany

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Hanover, Germany

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Krefeld, Germany

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Mainz, Germany

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Münster, Germany

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Saint Augustin, Germany

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Stuttgart, Germany

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Tübingen, Germany

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Thessaloniki, Greece

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Budapest, Hungary

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Haifa, Israel

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Kfar Saba, Israel

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Petah Tikva, Israel

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Ramat Gan, Israel

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Rehovot, Israel

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Bologna, Italy

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Florence, Italy

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Genova, Italy

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Milan, Italy

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Napoli, Italy

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Padua, Italy

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Rome, Italy

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Scafati, Italy

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Torino, Italy

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Utrecht, Netherlands

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Oslo, Norway

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Lima, Peru

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Warsaw, Poland

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Berea, Durban, South Africa

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Mayville, Durban, South Africa

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Pretoria, South Africa

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Barcelona, Spain

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Madrid, Spain

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Valencia, Spain

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Stockholm, Sweden

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Bern, Switzerland

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Lausanne, Switzerland

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Zurich, Switzerland

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Ankara, Turkey (Türkiye)

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Istanbul, Turkey (Türkiye)

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Izmir, Turkey (Türkiye)

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Birmingham, United Kingdom

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Liverpool, United Kingdom

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London, United Kingdom

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Manchester, United Kingdom

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New Castle Upon Tyne, United Kingdom

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Norwich, United Kingdom

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Oxford, United Kingdom

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Related Publications (4)

• 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

• 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.

  PMID: 28115015 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

• 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.

  PMID: 23252526 DERIVED

Related Links

• Click here for more information about this study
• 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: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 22, 2009
• First Posted: April 23, 2009
• Study Start: July 1, 2009
• Primary Completion: December 1, 2010
• Study Completion: January 1, 2011
• Last Updated: March 29, 2017
• Results First Posted: April 9, 2012

Record last verified: 2017-02

Locations

BE (4); CA (5); DK (1); IT (9); ES (3); SE (1); GB (7); US (15); BR (4); TU (3); FR (4); HU (1); GR (1); NL (1); PE (1); PL (1); ZA (3); CH (3); AR (3); DE (15); NO (1); IL (5)