Single-dose Study to Assess Efficacy of Canakinumab (ACZ885) in Patients With Active Juvenile Idiopathic Arthritis (SJIA) (β-SPECIFIC 1)
28 de fevereiro de 2017 atualizado por: 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.
Visão geral do estudo
Status
Rescindido
Condições
Intervenção / Tratamento
Tipo de estudo
Intervencional
Inscrição (Real)
84
Estágio
- Fase 3
Contactos e Locais
Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.
Locais de estudo
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Bad Bamstedt, Alemanha
- Novartis Investigative Site
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Berlin, Alemanha
- Novartis Investigative Site
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Bremen, Alemanha
- Novartis Investigative Site
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Dresden, Alemanha
- Novartis Investigative Site
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Freiburg, Alemanha
- Novartis Investigative Site
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Garmisch-Partenkirch, Alemanha
- Novartis Investigative Site
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Geissen, Alemanha
- Novartis Investigative Site
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Hamburg, Alemanha
- Novartis Investigative Site
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Hannover, Alemanha
- Novartis Investigative Site
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Krefeld, Alemanha
- Novartis Investigative Site
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Mainz, Alemanha
- Novartis Investigative Site
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Muenster, Alemanha
- Novartis Investigative Site
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Saint Augustin, Alemanha
- Novartis Investigative Site
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Stuttgart, Alemanha
- Novartis Investigative Site
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Tubingen, Alemanha
- Novartis Investigative Site
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Buenos Aires, Argentina
- Novartis Investigative Site
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Capital Federal, Argentina
- Novartis Investigative Site
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La Plata, Argentina
- Novartis Investigative Site
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Curitiba, Brasil
- Novartis Investigative Site
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Porto Alegre, Brasil
- Novartis Investigative Site
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Rio de Janeiro, Brasil
- Novartis Investigative Site
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Sao Paulo, Brasil
- Novartis Investigative Site
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Bruxelles, Bélgica
- Novartis Investigative Site
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Gent, Bélgica
- Novartis Investigative Site
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Laeken, Bélgica
- Novartis Investigative Site
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Leuven, Bélgica
- Novartis Investigative Site
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Calgary, Canadá
- Novartis Investigative Site
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British Columbia
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Vancouver, British Columbia, Canadá
- Novartis Investigative Site
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Nova Scotia
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Halifax, Nova Scotia, Canadá
- Novartis Investigative Site
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Ontario
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Toronto, Ontario, Canadá
- Novartis Investigative Site
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Quebec
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Montreal, Quebec, Canadá
- Novartis Investigative Site
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Arhus N, Dinamarca
- Novartis Investigative Site
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Barcelona, Espanha
- Novartis Investigative Site
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Madrid, Espanha
- Novartis Investigative Site
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Valencia, Espanha
- Novartis Investigative Site
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Alabama
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Birmingham, Alabama, Estados Unidos, 35233
- University of Alabama at Birmingham
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Arkansas
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Little Rock, Arkansas, Estados Unidos, 72202
- Arkansas Children's Hospital Research Inst
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California
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Los Angeles, California, Estados Unidos, 90027
- Children's Hospital Los Angeles
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District of Columbia
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Washington, District of Columbia, Estados Unidos, 20010
- Children's National Medical Center
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Illinois
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Chicago, Illinois, Estados Unidos, 60637
- University of Chicago Medical Center
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Kentucky
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Louisville, Kentucky, Estados Unidos, 40202
- University of Louisville
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Massachusetts
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Boston, Massachusetts, Estados Unidos, 02111
- Tufts Medical Center
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Boston, Massachusetts, Estados Unidos, 02111
- Tufts New England Medical Center-Dept. of Allergy
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New Jersey
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Livingston, New Jersey, Estados Unidos, 07039
- St. Barnabas Ambulatory Care Center
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Ohio
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Cincinnati, Ohio, Estados Unidos, 45229
- Children's Hospital Medical Center
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Cinncinati, Ohio, Estados Unidos, 45229
- Children's Hospital/Neurology
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Columbus, Ohio, Estados Unidos, 43205
- Nationwide Children's Hospital
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Oregon
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Portland, Oregon, Estados Unidos, 97227
- Legacy Emanuel Hospital
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Portland, Oregon, Estados Unidos, 97232
- Legacy Emanual Research
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Texas
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Austin, Texas, Estados Unidos, 78723
- Specially For Children
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Le Kremlin Bicetre, França
- Novartis Investigative Site
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Lyon, França
- Novartis Investigative Site
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Paris, França
- Novartis Investigative Site
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Strassbourg, França
- Novartis Investigative Site
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Thessaloniki, Grécia
- Novartis Investigative Site
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Utrecht, Holanda
- Novartis Investigative Site
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Budapest, Hungria
- Novartis Investigative Site
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Haifa, Israel
- Novartis Investigative Site
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Kfar Saba, Israel
- Novartis Investigative Site
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Petach-Tikva, Israel
- Novartis Investigative Site
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Ramat Gan, Israel
- Novartis Investigative Site
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Rehovot, Israel
- Novartis Investigative Site
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Bologna, Itália
- Novartis Investigative Site
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Firenze, Itália
- Novartis Investigative Site
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Genova, Itália
- Novartis Investigative Site
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Milano, Itália
- Novartis Investigative Site
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Napoli, Itália
- Novartis Investigative Site
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Padova, Itália
- Novartis Investigative Site
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Rome, Itália
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Scafati, Itália
- Novartis Investigative Site
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Torino, Itália
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Oslo, Noruega
- Novartis Investigative Site
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Ankara, Peru
- Novartis Investigative Site
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Istanbul, Peru
- Novartis Investigative Site
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Izmir, Peru
- Novartis Investigative Site
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Lima, Peru
- Novartis Investigative Site
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Warszawa, Polônia
- Novartis Investigative Site
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Birmingham, Reino Unido
- Novartis Investigative Site
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Liverpool, Reino Unido
- Novartis Investigative Site
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London, Reino Unido
- Novartis Investigative Site
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Manchester, Reino Unido
- Novartis Investigative Site
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New Castle Upon Tyne, Reino Unido
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Norwich, Reino Unido
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Oxford, Reino Unido
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Stockholm, Suécia
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Bern, Suíça
- Novartis Investigative Site
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Lausanne, Suíça
- Novartis Investigative Site
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Zurich, Suíça
- Novartis Investigative Site
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Pretoria, África do Sul
- Novartis Investigative Site
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Durban
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Berea, Durban, África do Sul
- Novartis Investigative Site
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Mayville, Durban, África do Sul
- Novartis Investigative Site
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Critérios de participação
Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.
Critérios de elegibilidade
Idades elegíveis para estudo
2 anos a 19 anos (Filho, Adulto)
Aceita Voluntários Saudáveis
Não
Gêneros Elegíveis para o Estudo
Tudo
Descrição
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
Plano de estudo
Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: Randomizado
- Modelo Intervencional: Atribuição Paralela
- Mascaramento: Quadruplicar
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
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Experimental: 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.
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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.
Outros nomes:
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Comparador de Placebo: Placebo
Patients received a single dose matching placebo of canakinumab on day 1.
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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.
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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Percentage of Patients Who Meet the Adapted American College of Rheumatology (ACR) Pediatric 30 Criteria
Prazo: Baseline, Day 15, Day 29
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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)
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Baseline, Day 15, Day 29
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Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Percentage of Patients Achieving the Adapted ACR Pediatric 50 Criteria
Prazo: Baseline, Day 15, Day 29
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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)
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Baseline, Day 15, Day 29
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Percentage of Patients Achieving the Adapted ACR Pediatric 70
Prazo: Baseline, Day 15, Day 29
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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)
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Baseline, Day 15, Day 29
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Percentage of Patients Achieving the Adapted ACR Pediatric 90
Prazo: Baseline, Day 15, Day 29
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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)
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Baseline, Day 15, Day 29
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Percentage of Patients Achieving the Adapted ACR Pediatric 100
Prazo: baseline, Day 15, Day 29
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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
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baseline, Day 15, Day 29
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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)
Prazo: Baseline, Day 15
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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.
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Baseline, Day 15
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Change in Patient's Pain Intensity as Assessed on a 100-mm Visual Analog Scale (VAS) as Part of CHAQ
Prazo: Baseline, Day 29
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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.
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Baseline, Day 29
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Percentage of Patients Who Had Body Temperature ≤ 38°C
Prazo: Day 3
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Body temperature was derived from vital signs evaluation.
No conversion of body temperature was performed, no matter how it was measured.
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Day 3
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Change in Health-related Quality of Life (HRQoL)Over Time by Use of the Child Health Questionnaire - Parent Form (CHQ-PF50)
Prazo: Over 4 week study period (Baseline, Day 15, Day 29)
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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.
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Over 4 week study period (Baseline, Day 15, Day 29)
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Change in Disability Score Over Time by Use of the CHAQ
Prazo: At 4 week study period
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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.
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At 4 week study period
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Colaboradores e Investigadores
É aqui que você encontrará pessoas e organizações envolvidas com este estudo.
Publicações e links úteis
A pessoa responsável por inserir informações sobre o estudo fornece voluntariamente essas publicações. Estes podem ser sobre qualquer coisa relacionada ao estudo.
Publicações Gerais
- 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.
Datas de registro do estudo
Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.
Datas Principais do Estudo
Início do estudo
1 de julho de 2009
Conclusão Primária (Real)
1 de dezembro de 2010
Conclusão do estudo (Real)
1 de janeiro de 2011
Datas de inscrição no estudo
Enviado pela primeira vez
22 de abril de 2009
Enviado pela primeira vez que atendeu aos critérios de CQ
22 de abril de 2009
Primeira postagem (Estimativa)
23 de abril de 2009
Atualizações de registro de estudo
Última Atualização Postada (Real)
29 de março de 2017
Última atualização enviada que atendeu aos critérios de controle de qualidade
28 de fevereiro de 2017
Última verificação
1 de fevereiro de 2017
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
Outros números de identificação do estudo
- CACZ885G2305
- EudraCT: 2008-005476-27
Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .