Single-dose Study to Assess Efficacy of Canakinumab (ACZ885) in Patients With Active Juvenile Idiopathic Arthritis (SJIA) (β-SPECIFIC 1)
28 febbraio 2017 aggiornato da: Novartis Pharmaceuticals
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
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.
Panoramica dello studio
Stato
Terminato
Condizioni
Intervento / Trattamento
Tipo di studio
Interventistico
Iscrizione (Effettivo)
84
Fase
- Fase 3
Contatti e Sedi
Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.
Luoghi di studio
-
-
-
Buenos Aires, Argentina
- Novartis Investigative Site
-
Capital Federal, Argentina
- Novartis Investigative Site
-
La Plata, Argentina
- Novartis Investigative Site
-
-
-
-
-
Bruxelles, Belgio
- Novartis Investigative Site
-
Gent, Belgio
- Novartis Investigative Site
-
Laeken, Belgio
- Novartis Investigative Site
-
Leuven, Belgio
- Novartis Investigative Site
-
-
-
-
-
Curitiba, Brasile
- Novartis Investigative Site
-
Porto Alegre, Brasile
- Novartis Investigative Site
-
Rio de Janeiro, Brasile
- Novartis Investigative Site
-
Sao Paulo, Brasile
- Novartis Investigative Site
-
-
-
-
-
Calgary, Canada
- Novartis Investigative Site
-
-
British Columbia
-
Vancouver, British Columbia, Canada
- Novartis Investigative Site
-
-
Nova Scotia
-
Halifax, Nova Scotia, Canada
- Novartis Investigative Site
-
-
Ontario
-
Toronto, Ontario, Canada
- Novartis Investigative Site
-
-
Quebec
-
Montreal, Quebec, Canada
- Novartis Investigative Site
-
-
-
-
-
Arhus N, Danimarca
- Novartis Investigative Site
-
-
-
-
-
Le Kremlin Bicetre, Francia
- Novartis Investigative Site
-
Lyon, Francia
- Novartis Investigative Site
-
Paris, Francia
- Novartis Investigative Site
-
Strassbourg, Francia
- Novartis Investigative Site
-
-
-
-
-
Bad Bamstedt, Germania
- Novartis Investigative Site
-
Berlin, Germania
- Novartis Investigative Site
-
Bremen, Germania
- Novartis Investigative Site
-
Dresden, Germania
- Novartis Investigative Site
-
Freiburg, Germania
- Novartis Investigative Site
-
Garmisch-Partenkirch, Germania
- Novartis Investigative Site
-
Geissen, Germania
- Novartis Investigative Site
-
Hamburg, Germania
- Novartis Investigative Site
-
Hannover, Germania
- Novartis Investigative Site
-
Krefeld, Germania
- Novartis Investigative Site
-
Mainz, Germania
- Novartis Investigative Site
-
Muenster, Germania
- Novartis Investigative Site
-
Saint Augustin, Germania
- Novartis Investigative Site
-
Stuttgart, Germania
- Novartis Investigative Site
-
Tubingen, Germania
- Novartis Investigative Site
-
-
-
-
-
Thessaloniki, Grecia
- Novartis Investigative Site
-
-
-
-
-
Haifa, Israele
- Novartis Investigative Site
-
Kfar Saba, Israele
- Novartis Investigative Site
-
Petach-Tikva, Israele
- Novartis Investigative Site
-
Ramat Gan, Israele
- Novartis Investigative Site
-
Rehovot, Israele
- Novartis Investigative Site
-
-
-
-
-
Bologna, Italia
- Novartis Investigative Site
-
Firenze, Italia
- Novartis Investigative Site
-
Genova, Italia
- Novartis Investigative Site
-
Milano, Italia
- Novartis Investigative Site
-
Napoli, Italia
- Novartis Investigative Site
-
Padova, Italia
- Novartis Investigative Site
-
Rome, Italia
- Novartis Investigative Site
-
Scafati, Italia
- Novartis Investigative Site
-
Torino, Italia
- Novartis Investigative Site
-
-
-
-
-
Oslo, Norvegia
- Novartis Investigative Site
-
-
-
-
-
Utrecht, Olanda
- Novartis Investigative Site
-
-
-
-
-
Lima, Perù
- Novartis Investigative Site
-
-
-
-
-
Warszawa, Polonia
- Novartis Investigative Site
-
-
-
-
-
Birmingham, Regno Unito
- Novartis Investigative Site
-
Liverpool, Regno Unito
- Novartis Investigative Site
-
London, Regno Unito
- Novartis Investigative Site
-
Manchester, Regno Unito
- Novartis Investigative Site
-
New Castle Upon Tyne, Regno Unito
- Novartis Investigative Site
-
Norwich, Regno Unito
- Novartis Investigative Site
-
Oxford, Regno Unito
- Novartis Investigative Site
-
-
-
-
-
Barcelona, Spagna
- Novartis Investigative Site
-
Madrid, Spagna
- Novartis Investigative Site
-
Valencia, Spagna
- Novartis Investigative Site
-
-
-
-
Alabama
-
Birmingham, Alabama, Stati Uniti, 35233
- University of Alabama at Birmingham
-
-
Arkansas
-
Little Rock, Arkansas, Stati Uniti, 72202
- Arkansas Children's Hospital Research Inst
-
-
California
-
Los Angeles, California, Stati Uniti, 90027
- Children's Hospital Los Angeles
-
-
District of Columbia
-
Washington, District of Columbia, Stati Uniti, 20010
- Children's National Medical Center
-
-
Illinois
-
Chicago, Illinois, Stati Uniti, 60637
- University Of Chicago Medical Center
-
-
Kentucky
-
Louisville, Kentucky, Stati Uniti, 40202
- University of Louisville
-
-
Massachusetts
-
Boston, Massachusetts, Stati Uniti, 02111
- Tufts Medical Center
-
Boston, Massachusetts, Stati Uniti, 02111
- Tufts New England Medical Center-Dept. of Allergy
-
-
New Jersey
-
Livingston, New Jersey, Stati Uniti, 07039
- St. Barnabas Ambulatory Care Center
-
-
Ohio
-
Cincinnati, Ohio, Stati Uniti, 45229
- Children's Hospital Medical Center
-
Cinncinati, Ohio, Stati Uniti, 45229
- Children's Hospital/Neurology
-
Columbus, Ohio, Stati Uniti, 43205
- Nationwide Children's Hospital
-
-
Oregon
-
Portland, Oregon, Stati Uniti, 97227
- Legacy Emanuel Hospital
-
Portland, Oregon, Stati Uniti, 97232
- Legacy Emanual Research
-
-
Texas
-
Austin, Texas, Stati Uniti, 78723
- Specially For Children
-
-
-
-
-
Pretoria, Sud Africa
- Novartis Investigative Site
-
-
Durban
-
Berea, Durban, Sud Africa
- Novartis Investigative Site
-
Mayville, Durban, Sud Africa
- Novartis Investigative Site
-
-
-
-
-
Stockholm, Svezia
- Novartis Investigative Site
-
-
-
-
-
Bern, Svizzera
- Novartis Investigative Site
-
Lausanne, Svizzera
- Novartis Investigative Site
-
Zurich, Svizzera
- Novartis Investigative Site
-
-
-
-
-
Ankara, Tacchino
- Novartis Investigative Site
-
Istanbul, Tacchino
- Novartis Investigative Site
-
Izmir, Tacchino
- Novartis Investigative Site
-
-
-
-
-
Budapest, Ungheria
- Novartis Investigative Site
-
-
Criteri di partecipazione
I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.
Criteri di ammissibilità
Età idonea allo studio
Da 2 anni a 19 anni (Bambino, Adulto)
Accetta volontari sani
No
Sessi ammissibili allo studio
Tutto
Descrizione
Inclusion 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:
- 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
- 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:
- 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
- Other protocol defined exclusion criteria may apply
Piano di studio
Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
- Assegnazione: Randomizzato
- Modello interventistico: Assegnazione parallela
- Mascheramento: Quadruplicare
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
|---|---|
|
Sperimentale: Canakinumab
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.
|
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.
Altri nomi:
|
|
Comparatore placebo: Placebo
Patients received a single dose matching placebo of canakinumab on day 1.
|
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.
|
Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
|
Percentage of Patients Who Meet the Adapted American College of Rheumatology (ACR) Pediatric 30 Criteria
Lasso di tempo: Baseline, Day 15, Day 29
|
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
|
Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
|
Percentage of Patients Achieving the Adapted ACR Pediatric 50 Criteria
Lasso di tempo: Baseline, Day 15, Day 29
|
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
|
|
Percentage of Patients Achieving the Adapted ACR Pediatric 70
Lasso di tempo: Baseline, Day 15, Day 29
|
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
|
|
Percentage of Patients Achieving the Adapted ACR Pediatric 90
Lasso di tempo: Baseline, Day 15, Day 29
|
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
|
|
Percentage of Patients Achieving the Adapted ACR Pediatric 100
Lasso di tempo: baseline, Day 15, Day 29
|
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
|
|
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)
Lasso di tempo: Baseline, Day 15
|
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
|
|
Change in Patient's Pain Intensity as Assessed on a 100-mm Visual Analog Scale (VAS) as Part of CHAQ
Lasso di tempo: Baseline, Day 29
|
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
|
|
Percentage of Patients Who Had Body Temperature ≤ 38°C
Lasso di tempo: Day 3
|
Body temperature was derived from vital signs evaluation.
No conversion of body temperature was performed, no matter how it was measured.
|
Day 3
|
|
Change in Health-related Quality of Life (HRQoL)Over Time by Use of the Child Health Questionnaire - Parent Form (CHQ-PF50)
Lasso di tempo: Over 4 week study period (Baseline, Day 15, Day 29)
|
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)
|
|
Change in Disability Score Over Time by Use of the CHAQ
Lasso di tempo: At 4 week study period
|
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
|
Collaboratori e investigatori
Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.
Pubblicazioni e link utili
La persona responsabile dell'inserimento delle informazioni sullo studio fornisce volontariamente queste pubblicazioni. Questi possono riguardare qualsiasi cosa relativa allo studio.
Pubblicazioni generali
- 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.
- 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.
- 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.
- 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.
Collegamenti utili
Studiare le date dei record
Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.
Studia le date principali
Inizio studio
1 luglio 2009
Completamento primario (Effettivo)
1 dicembre 2010
Completamento dello studio (Effettivo)
1 gennaio 2011
Date di iscrizione allo studio
Primo inviato
22 aprile 2009
Primo inviato che soddisfa i criteri di controllo qualità
22 aprile 2009
Primo Inserito (Stima)
23 aprile 2009
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
29 marzo 2017
Ultimo aggiornamento inviato che soddisfa i criteri QC
28 febbraio 2017
Ultimo verificato
1 febbraio 2017
Maggiori informazioni
Termini relativi a questo studio
Parole chiave
Termini MeSH pertinenti aggiuntivi
Altri numeri di identificazione dello studio
- CACZ885G2305
- EudraCT: 2008-005476-27
Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .