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

Systemic Juvenile Idiopathic Arthritis Clinical Trial

— ß-SPECIFIC 1  

Official title:

A Randomized, Double-blind, Placebo Controlled, Single-dose Study to Assess the Initial Efficacy of Canakinumab (ACZ885) With Respect to the Adapted ACR Pediatric 30 Criteria in Patients With Systemic Juvenile Idiopathic Arthritis (SJIA) and Active Systemic Manifestations

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00886769
• Other study ID #: CACZ885G2305
• Secondary ID: EudraCT: 2008-00
• Status: Terminated
• Phase: Phase 3
• First received: April 22, 2009
• Last updated: March 13, 2012
• Start date: July 2009
• Est. completion date: January 2011

Study information

• Verified date: March 2012
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationArgentina: Ministry of HealthBrazil: Ministry of HealthBelgium: Federal Agency for Medicinal Products and Health ProductsCanada: Health CanadaFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Germany: Paul-Ehrlich-InstitutHungary: National Institute of PharmacyIsrael: Ministry of HealthItaly: Ministry of HealthNorway: Norwegian Medicines AgencyNetherlands: The Central Committee on Research Involving Human Subjects (CCMO)Peru: Ministry of HealthPoland: Office for Registration of Medicinal Products, Medical Devices and Biocidal ProductsSouth Africa: Medicines Control CouncilSpain: Spanish Agency of MedicinesSweden: Medical Products AgencySwitzerland: SwissmedicTurkey: Ministry of HealthUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyDenmark: Ethics Committee
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 84
• Est. completion date: January 2011
• Est. primary completion date: December 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 2 Years to 19 Years

Eligibility

Inclusion Criteria:

1. 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

2. 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

3. Male and female patients aged = 2 to < 20 years of age

4. 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)

5. Naïve to canakinumab

6. Other protocol defined inclusion criteria may apply

Exclusion Criteria:

Patients who fulfilled one or more of the following criteria were not eligible for inclusion in this study:

1. Pregnant or nursing (lactating) female patients

2. 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

3. History of hypersensitivity to study drug or to biologics.

4. Diagnosis of active macrophage-activation syndrome (MAS) (Ravelli, Magni-Manzoni and Pistorio 2005) within the last 6 months

5. 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

6. Other protocol defined exclusion criteria may apply

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Juvenile
• Systemic Juvenile Idiopathic Arthritis

Intervention

Drug:
• Canakinumab
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.
• Placebo
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.

Locations

Country	Name	City	State
Argentina	Novartis Investigative Site	Buenos Aires
Argentina	Novartis Investigative Site	Capital Federal
Argentina	Novartis Investigative Site	La Plata
Belgium	Novartis Investigative site	Bruxelles
Belgium	Novartis Investigative site	Gent
Belgium	Novartis Investigative Site	Laeken
Belgium	Novartis Investigative site	Leuven
Brazil	Novartis Investigative Site	Curitiba
Brazil	Novartis Investigative site	Porto Alegre
Brazil	Novartis Investigative site	Rio de Janeiro
Brazil	Novartis Investigative site	Sao Paulo
Canada	Novartis Investigative site	Calgary
Canada	Novartis Investigative site	Halifax	Nova Scotia
Canada	Novartis Investigative site	Montreal	Quebec
Canada	Novartis Investigative site	Toronto	Ontario
Canada	Novartis Investigative site	Vancouver	British Columbia
Denmark	Novartis Investigative site	Arhus N
France	Novartis Investigative Site	Le Kremlin Bicetre
France	Novartis Investigative Site	Lyon
France	Novartis Investigative Site	Paris
France	Novartis Investigative Site	Strassbourg
Germany	Novartis Investigative Site	Bad Bamstedt
Germany	Novartis Investigative site	Berlin
Germany	Novartis Investigative Site	Bremen
Germany	Novartis Investigative site	Dresden
Germany	Novartis Investigative Site	Freiburg
Germany	Novartis Investigative site	Garmisch-Partenkirch
Germany	Novartis Investigative Site	Geissen
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative site	Hannover
Germany	Novartis Investigative site	Krefeld
Germany	Novartis Investigative site	Mainz
Germany	Novartis Investigative Site	Muenster
Germany	Novartis Investigative Site	Saint Augustin
Germany	Novartis Investigative Site	Stuttgart
Germany	Novartis Investigative site	Tubingen
Greece	Novartis Investigative site	Thessaloniki
Hungary	Novartis Investigative Site	Budapest
Israel	Novartis Investigative Site	Haifa
Israel	Novartis Investigative Site	Kfar Saba
Israel	Novartis Investigative Site	Petach-Tikva
Israel	Novartis Investigative Site	Ramat Gan
Israel	Novartis Investigative Site	Rehovot
Italy	Novartis Investigative Site	Bologna
Italy	Novartis Investigative Site	Firenze
Italy	Novartis Investigative Site	Genova
Italy	Novartis Investigative site	Milano
Italy	Novartis Investigative site	Napoli
Italy	Novartis Investigative site	Padova
Italy	Novartis Investigative site	Rome
Italy	Novartis Investigative site	Scafati
Italy	Novartis Investigative site	Torino
Netherlands	Novartis Investigative site	Utrecht
Norway	Novartis Investigative Site	Oslo
Peru	Novartis Investigative Site	Lima
Poland	Novartis Investigative site	Warszawa
South Africa	Novartis Investigative site	Berea	Durban
South Africa	Novartis Investigative site	Mayville	Durban
South Africa	Novartis Investigative site	Pretoria
Spain	Novartis Investigative site	Barcelona
Spain	Novartis Investigative site	Madrid
Spain	Novartis Investigative site	Valencia
Sweden	Novartis Investigative site	Stockholm
Switzerland	Novartis Investigative Site	Bern
Switzerland	Novartis Investigative site	Lausanne
Switzerland	Novartis Investigative site	Zurich
Turkey	Novartis Investigative site	Ankara
Turkey	Novartis Investigative Site	Istanbul
Turkey	Novartis Investigative Site	Izmir
United Kingdom	Novartis Investigative site	Birmingham
United Kingdom	Novartis Investigative site	Liverpool
United Kingdom	Novartis Investigative site	London
United Kingdom	Novartis Investigative site	Manchester
United Kingdom	Novartis Investigative site	New Castle Upon Tyne
United Kingdom	Novartis Investigative site	Norwich
United Kingdom	Novartis Investigative site	Oxford
United States	Specially For Children	Austin	Texas
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Tufts Medical Center	Boston	Massachusetts
United States	Tufts New England Medical Center-Dept. of Allergy	Boston	Massachusetts
United States	University of Chicago Medical Center	Chicago	Illinois
United States	Children's Hospital Medical Center	Cincinnati	Ohio
United States	Children's Hospital/Neurology	Cinncinati	Ohio
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	Arkansas Children's Hospital Research Inst	Little Rock	Arkansas
United States	St. Barnabas Ambulatory Care Center	Livingston	New Jersey
United States	Children's Hospital Los Angeles	Los Angeles	California
United States	University of Louisville	Louisville	Kentucky
United States	Legacy Emanual Research	Portland	Oregon
United States	Legacy Emanuel Hospital	Portland	Oregon
United States	Children's National Medical Center	Washington	District of Columbia

Sponsors (3)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals	International Maternal Pediatric Adolescent AIDS Clinical Trials Group, Southwest Pediatric Nephrology Study Group

Countries where clinical trial is conducted

United States,  Argentina,  Belgium,  Brazil,  Canada,  Denmark,  France,  Germany,  Greece,  Hungary,  Israel,  Italy,  Netherlands,  Norway,  Peru,  Poland,  South Africa,  Spain,  Sweden,  Switzerland,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Percentage of Patients Achieving the Adapted ACR Pediatric 50 Criteria	Adapted ACR Pediatric 50 criteria determined responders (improved from baseline of at least 50% 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	No
Secondary	Percentage of Patients Achieving the Adapted ACR Pediatric 70	Adapted ACR Pediatric 70 criteria determined responders (improved from baseline of at least 70% 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	No
Secondary	Percentage of Patients Achieving the Adapted ACR Pediatric 90	Adapted ACR Pediatric 90 criteria determined responders (improved from baseline of at least 90% 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	No
Secondary	Percentage of Patients Achieving the Adapted ACR Pediatric 100	Adapted ACR Pediatric 100 criteria determined responders (ie improved from baseline of at least 100% 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	baseline, Day 15, Day 29	No
Secondary	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)	CHAQ assessed physical ability and functional status of patients as well as quality of life. The disability dimension consisted of 20 multiple choice items about difficulty in doing eight common activities of daily living; dressing and grooming, arising, eating, walking, reaching, personal hygiene, gripping and activities. Four response categories range from 'without any difficulty' (0) to 'unable to do' (3). The parent's or patient's pain assessment was on VAS that was part of CHAQ. The VAS scale ranges from no pain (0 mm) to very severe pain (100 mm). Negative change indicates improvement.	Baseline, Day 15	No
Secondary	Change in Patient's Pain Intensity as Assessed on a 100-mm Visual Analog Scale (VAS) as Part of CHAQ	CHAQ, assessed physical ability and functional status of patients as well as quality of life. The disability dimension consisted of 20 multiple choice items about difficulty in doing eight common activities of daily living; dressing and grooming, arising, eating, walking, reaching, personal hygiene, gripping and activities. Four response categories range from 'without any difficulty'(0) to 'unable to do' (3). The parent's or patient's pain assessment was on VAS that was part of CHAQ. The VAS scale ranges from no pain (0 mm) to very severe pain (100 mm). Negative change indicates improvement.	Baseline, Day 29	No
Secondary	Percentage of Patients Who Had Body Temperature = 38°C	Body temperature was derived from vital signs evaluation. No conversion of body temperature was performed, no matter how it was measured.	Day 3	No
Secondary	Change in Health-related Quality of Life (HRQoL)Over Time by Use of the Child Health Questionnaire - Parent Form (CHQ-PF50)	CHQ-PF50 measures HRQoL in children 5-18 years old from parent's perspective. Questionnaire completed by parent without input from patient. Total score ranges from 0-100. Increases in scores represent improved well-being in subjects as assessed by their parents. Mixed linear model on change from baseline in CHQ-PF50 score with treatment group, stratification factors, day of assessment and interaction between group and day as covariates. Covariance analysis used a repeated measures approach, so all timepoints over time were taken into account.	Over 4 week study period (Baseline, Day 15, Day 29)	No
Secondary	Change in Disability Score Over Time by Use of the CHAQ	The disability dimension of CHAQ consisted of 20 multiple choice items about difficulty in doing eight common activities of daily living; dressing and grooming, arising, eating, walking, reaching, personal hygiene, gripping and activities. Four response categories range from 'without any difficulty'(0) to 'unable to do' (3). Mixed linear model on change from baseline in CHAQ score included treatment group, stratification factors, day of assessment and interaction between group and day as covariates. Negative change indicates improvement.	At 4 week study period	No

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