Double Blind, Placebo-controlled, Study of the Safety, Tolerability and Pharmacokinetics of AIN457 in Rheumatoid Arthritis Patients
27 de março de 2015 atualizado por: Novartis Pharmaceuticals
A Randomized, Double Blind, Placebo-controlled, Dose Escalation Study of the Safety, Tolerability and Pharmacokinetics of AIN457 in Rheumatoid Arthritis Patients With Pharmacodynamics Assessed in an Expanded Cohort at the Maximum Tolerated Dose
Evaluate the safety, tolerability and pharmacokinetics of AIN457 when administered as a single dose (intravenous infusion) in patients with active rheumatoid arthritis in combination with a stable dose of methotrexate.
And to compare efficacy on the dose groups.
Visão geral do estudo
Status
Concluído
Condições
Intervenção / Tratamento
Tipo de estudo
Intervencional
Inscrição (Real)
104
Estágio
- Fase 2
- Fase 1
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 Nauheim, Alemanha, 61231
- Novartis Investigative Site
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Erlangen, Alemanha, 91054
- Novartis Investigative Site
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Muenchen, Alemanha, 80336
- Novartis Investigative Site
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Bruxelles, Bélgica, 1200
- Novartis Investigative Site
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Merksem, Bélgica, 2170
- Novartis Investigative Site
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Singapore, Cingapura, 119074
- Novartis Investigative Site
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Singapore, Cingapura, 529889
- Novartis Investigative Site
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Guadalajara, Espanha, 19002
- Novartis Investigative Site
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Galicia
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La Coruna, Galicia, Espanha, 15006
- Novartis Investigative Site
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Santiago de Compostela, Galicia, Espanha, 15706
- Novartis Investigative Site
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Alabama
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Anniston, Alabama, Estados Unidos, 36207-5710
- Novartis Investigative Site
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Arizona
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Tucson, Arizona, Estados Unidos, 85724
- Novartis Investigative Site
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Florida
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Largo, Florida, Estados Unidos, 33773
- Novartis Investigative Site
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Ocala, Florida, Estados Unidos, 34471
- Novartis Investigative Site
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Palm Harbor, Florida, Estados Unidos, 34684
- Novartis Investigative Site
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Port Orange, Florida, Estados Unidos, 32127
- Novartis Investigative Site
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Kentucky
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Madisonville, Kentucky, Estados Unidos, 42431
- Novartis Investigative Site
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Missouri
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St. Louis, Missouri, Estados Unidos, 63110
- Novartis Investigative Site
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Nebraska
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Omaha, Nebraska, Estados Unidos, 68131-2197
- Novartis Investigative Site
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Oklahoma
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Oklahoma City, Oklahoma, Estados Unidos, 73103
- Novartis Investigative Site
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Oregon
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Bend, Oregon, Estados Unidos, 97701
- Novartis Investigative Site
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Pennsylvania
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Duncansville, Pennsylvania, Estados Unidos, 16635
- Novartis Investigative Site
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Amsterdam, Holanda, 1105 AZ
- Novartis Investigative Site
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Nijmegen, Holanda, 6525 GA
- 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
18 anos a 75 anos (Adulto, Adulto mais velho)
Aceita Voluntários Saudáveis
Não
Gêneros Elegíveis para o Estudo
Tudo
Descrição
Inclusion Criteria:
- Male and female patients with active rheumatoid arthritis in combination with a stable dose of methotrexate aged 18-75 years may participate in this trial.
- Post menopausal or surgically sterile female patients are allowed. Women of child-bearing potential may participate if they are on a stable dose of methotrexate and if they are practicing effective contraception for at least 6 months prior to screening, willing to use 2 forms of contraception, including at least 1 barrier method during the study and for at least 2 months following the completion/discontinuation of the study.
- Patients must have a diagnosis of active rheumatoid arthritis of stages I, II or III (ACR 1987 revised classification for criteria for RA). Disease duration of at least 6 months prior to randomization is essential;
Exclusion Criteria:
- Current treatment with anti-TNF-α or anti IL-1 therapy (or other biological therapy).
- Patients with congestive heart failure or poorly controlled diabetes mellitus (HbA1c value ≥10%).
- Presence of any major chronic inflammatory autoimmune diseases like psoriasis, psoriatic arthritis, spondyloarthropathy, inflammatory bowel disease or SLE that can mimic rheumatoid arthritis diagnosis or that can interfere with efficacy evaluation in the study.
- History of renal trauma, glomerulonephritis or patient with one kidney.
- Pregnant or breastfeeding women will be excluded.
- A positive tuberculin skin test.
Other protocol-defined inclusion/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: Ciência básica
- Alocação: Randomizado
- Modelo Intervencional: Atribuição Paralela
- Mascaramento: Dobro
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
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Experimental: Part 1 - AIN457A 10 mg/kg
AIN457A 10.0 mg/kg was administered intravenously as a single dose.
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AIN457A is a fully human recombinant IgG1 antibody that targets and neutralizes IL-17A.
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Experimental: Part 1 - AIN457A 0.3 mg/kg
AIN457A 0.3 mg/kg was administered intravenously as a single dose.
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AIN457A is a fully human recombinant IgG1 antibody that targets and neutralizes IL-17A.
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Experimental: Part 1 - AIN457A 1.0 mg/kg
AIN457A 1.0 mg/kg was administered intravenously as a single dose.
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AIN457A is a fully human recombinant IgG1 antibody that targets and neutralizes IL-17A.
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Experimental: Part 1 - AIN457A 3.0 mg/kg
AIN457A 3.0 mg/kg was administered intravenously as a single dose.
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AIN457A is a fully human recombinant IgG1 antibody that targets and neutralizes IL-17A.
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Comparador de Placebo: Part 1 - Placebo
Placebo to AIN457A was administered intravenously as a single dose.
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Placebo to AIN457
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Experimental: Parts 2 and 3 - AIN457A 1.0 mg/kg
AIN457A 1.0 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22.
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AIN457A is a fully human recombinant IgG1 antibody that targets and neutralizes IL-17A.
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Experimental: Parts 2 and 3 - AIN457A 3.0 mg/kg
AIN457A 3.0 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22.
|
AIN457A is a fully human recombinant IgG1 antibody that targets and neutralizes IL-17A.
|
|
Experimental: Parts 2 and 3 - AIN457A 10 mg/kg
AIN457A 10.0 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22.
|
AIN457A is a fully human recombinant IgG1 antibody that targets and neutralizes IL-17A.
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Comparador de Placebo: Parts 2 and 3 - Placebo
Placebo to AIN457A was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22.
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Placebo to AIN457
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Experimental: Part 1 - Healthy Volunteers - AIN457A 3 mg/kg
AIN457A 3.0 mg/kg was administered intravenously as a single dose.
|
AIN457A is a fully human recombinant IgG1 antibody that targets and neutralizes IL-17A.
|
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Experimental: Part 1 - Healthy Volunteers - AIN457A 10 mg/kg
AIN457A 10 mg/kg was administered intravenously as a single dose.
|
AIN457A is a fully human recombinant IgG1 antibody that targets and neutralizes IL-17A.
|
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Comparador de Placebo: Part 1 - Healthy Volunteers - Placebo
Placebo to AIN457A was administered intravenously as a single dose.
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Placebo to AIN457
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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 Parts 2 and 3 Participants Who Achieved American College of Rheumatology Response of 20 (ACR20)
Prazo: Day 43
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Clinical response to treatment was assessed according to ACR20 criteria.
A participant was defined as an ACR20 responder if the following 3 conditions were met: 1) ≥20% improvement in the number of tender joints, 2) ≥20% improvement in the number of swollen joint and 3) ≥20% improvement in three of the following five domains: patient global assessment, physician global assessment, patient pain assessment, health assessment questionnaire (HAQ) and acute phase reactant.
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Day 43
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Pharmacokinetics (PK) of AIN457: Time to Reach the Maximum Concentration After Drug Administration (Tmax) in Part 1 Participants
Prazo: Day 113
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Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 29, 36, 43, 57, 71, 85, 99 and 113.
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Day 113
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PK of AIN457: Observed Maximum Serum Concentration Following Drug Administration (Cmax) in Part 1 Participants
Prazo: Day 113
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Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 23, 26, 29, 36, 43, 57, 71, 85, 99 and 113.
On day 22, samples were collected pre-dose and 0.5, 1, 2, 4, 7 and 24 hours post infusion.
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Day 113
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PK of AIN457: Area Under the Serum Concentration-time Cure From Time Zero to the Time of Last Quantifiable Concentration (AUClast), Area Under the Serum Concentration-time Curve From Time Zero to (AUCinf) in Part 1 Participants
Prazo: Day 113
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Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 23, 26, 29, 36, 43, 57, 71, 85, 99 and 113.
On day 22, samples were collected pre-dose and 0.5, 1, 2, 4, 7 and 24 hours post infusion.
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Day 113
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PK of AIN457: Volume of Distribution During the Terminal Phase Following Intravenous Elimination (Vz) in Part 1 Participants
Prazo: Day 113
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Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 23, 26, 29, 36, 43, 57, 71, 85, 99 and 113.
On day 22, samples were collected pre-dose and 0.5, 1, 2, 4, 7 and 24 hours post infusion.
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Day 113
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PK of AIN457: Systemic Clearance From Serum Following Intravenous Administration (CL) in Part 1 Participants
Prazo: Day 113
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Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 23, 26, 29, 36, 43, 57, 71, 85, 99 and 113.
On day 22, samples were collected pre-dose and 0.5, 1, 2, 4, 7 and 24 hours post infusion.
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Day 113
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PK of AIN457: Terminal Elimination Half-life (T1/2) in Part 1 Participants
Prazo: Day 113
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Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 23, 26, 29, 36, 43, 57, 71, 85, 99 and 113.
On day 22, samples were collected pre-dose and 0.5, 1, 2, 4, 7 and 24 hours post infusion.
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Day 113
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Pharmacokinetics PK of AIN457: Tmax in Parts 2 and 3 Participants
Prazo: Day 113
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Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 23, 26, 29, 36, 43, 57, 71, 85, 99 and 113.
On day 22, samples were collected pre-dose and 0.5, 1, 2, 4, 7 and 24 hours post infusion.
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Day 113
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Pharmacokinetics PK of AIN457: Cmax in Parts 2 and 3 Participants
Prazo: Day 113
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Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 23, 26, 29, 36, 43, 57, 71, 85, 99 and 113.
On day 22, samples were collected pre-dose and 0.5, 1, 2, 4, 7 and 24 hours post infusion.
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Day 113
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Pharmacokinetics PK of AIN457: AUClast and AUCinf in Parts 2 and 3 Participants
Prazo: Day 113
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Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 23, 26, 29, 36, 43, 57, 71, 85, 99 and 113.
On day 22, samples were collected pre-dose and 0.5, 1, 2, 4, 7 and 24 hours post infusion.
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Day 113
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Pharmacokinetics PK of AIN457: Vz in Parts 2 and 3 Participants
Prazo: Day 113
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Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 23, 26, 29, 36, 43, 57, 71, 85, 99 and 113.
On day 22, samples were collected pre-dose and 0.5, 1, 2, 4, 7 and 24 hours post infusion.
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Day 113
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Pharmacokinetics PK of AIN457: CL in Parts 2 and 3 Participants
Prazo: Day 113
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Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 23, 26, 29, 36, 43, 57, 71, 85, 99 and 113.
On day 22, samples were collected pre-dose and 0.5, 1, 2, 4, 7 and 24 hours post infusion.
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Day 113
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Pharmacokinetics PK of AIN457: T1/2 in Parts 2 and 3 Participants
Prazo: Day 113
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Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 23, 26, 29, 36, 43, 57, 71, 85, 99 and 113.
On day 22, samples were collected pre-dose and 0.5, 1, 2, 4, 7 and 24 hours post infusion.
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Day 113
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Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
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Percentage of Parts 2 and 3 Participants Who Achieved ACR50 and ACR70
Prazo: Day 43
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Clinical response to treatment was assessed according to ACR50 and ACR70 criteria.
A participant was defined as an ACR50 or ACR70 responder if the following 3 conditions were met: 1) improvement of ≥50% or ≥ 70%, respectively, in the number of tender joints, 2) improvement of ≥50% or ≥ 70%, respectively, in the number of swollen joints and 3) improvement of ≥50% or ≥ 70%, respectively, in three of the following five domains: patient global assessment, physician global assessment, patient pain assessment, health assessment questionnaire (HAQ) and acute phase reactant
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Day 43
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Disease Activity Score (DAS28) of Parts 2 and 3 Participants
Prazo: Day 43
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The DAS28 is a composite score based on tender and swollen joint counts, C reactive protein (CRP) concentrations, and the participant's global disease activity based on a visual analogue scale (VAS).
The tender joint count (based on 28 joints) was calculated by scoring several different aspects of tenderness as assessed by pressure and joint manipulation on physical examination.
The information on various types of tenderness was then collapsed into a single tender versus non-tender dichotomy, and the number of joints that were classified as tender was recorded.
The swollen joint count was calculated in the same manner.
For CRP concentrations, blood samples were collected and sent to a central laboratory for assessment.
For the VAS assessment, the participant used a 100 mm horizontal VAS to assess the severity of his or her arthritis where 0 = none and 100 = most severe.
DAS28 scores range from <2.6 (disease remission) to >5.1 (high disease activity).
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Day 43
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Colaboradores e Investigadores
É aqui que você encontrará pessoas e organizações envolvidas com este estudo.
Patrocinador
Publicações e links úteis
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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 dezembro de 2005
Conclusão Primária (Real)
1 de novembro de 2008
Conclusão do estudo (Real)
1 de novembro de 2008
Datas de inscrição no estudo
Enviado pela primeira vez
29 de abril de 2008
Enviado pela primeira vez que atendeu aos critérios de CQ
30 de abril de 2008
Primeira postagem (Estimativa)
1 de maio de 2008
Atualizações de registro de estudo
Última Atualização Postada (Estimativa)
30 de março de 2015
Última atualização enviada que atendeu aos critérios de controle de qualidade
27 de março de 2015
Última verificação
1 de março de 2015
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
Outros números de identificação do estudo
- CAIN457A2101
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 .
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