A Study of the Safety and Efficacy of Golimumab in Subjects With Rheumatoid Arthritis That Are Methotrexate-naive
27 de agosto de 2014 actualizado por: Centocor, Inc.
A Multicenter, Randomized, Double-blind, Placebo-controlledTrial of Golimumab, a Fully Human Anti-TNFa MonoclonalAntibody, Administered Subcutaneously, in Methotrexate-naive Subjects With Active Rheumatoid Arthritis
The purpose of this study is to evaluate the efficacy and safety of golimumab, alone or in combination with methotrexate, as compared to methotrexate alone in rheumatoid arthritis subjects who have not been previously treated with methotrexate.
Descripción general del estudio
Estado
Terminado
Condiciones
Descripción detallada
Golimumab is a fully human protein (antibody) which binds to tumor necrosis factor (TNFa).
TNFa is increased in patients with rheumatoid arthritis (RA), and plays a major role in causing the joint pain, swelling, and damage from RA.
Other marketed drugs that target TNFa (anti-TNFa drugs) have been shown to be effective in reducing the symptoms, signs, and joint damage of RA, but have limitations with respect to safety and ease of use.
This is a randomized, double-blind, placebo-controlled trial of the efficacy and safety of a new anti-TNFa drug, golimumab, at 2 doses, injected under the skin every 4 weeks, alone or in combination with methotrexate, compared with methotrexate alone, in subjects with active RA who have not been previously treated with methotrexate.
The study hypothesis is that golimumab, alone or in combination with methotrexate, will be more effective in treatment of RA than methotrexate alone, as measured by the American College of Rheumatology (ACR) response criteria and change from baseline in van der Heide Modified Sharp (vdH-S) score, without causing unacceptable significant adverse effects.
The ACR response criteria were designed to determine the percentage of subjects who have achieved a certain level of improvement in their signs and symptoms of rheumatoid arthritis.
The vdH-S score is a measurement of the amount of joint damage in a subject as seen by x-ray.
Other secondary measures of effectiveness include the Health Assessment Questionnaire (HAQ), which is a series of questions that measure a subject's impairment in physical function caused by RA.
Golimumab 50 mg or 100 mg, or placebo injections under the skin every 4 weeks until Week52.
Methotrexate (MTX) or placebo capsules will be given in addition.
At Week52, subjects on MTX alone with joint pain or swelling get golimumab 50mg, and all subjects receive golimumab for about 4 more years.
Tipo de estudio
Intervencionista
Inscripción (Actual)
637
Fase
- Fase 3
Contactos y Ubicaciones
Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.
Ubicaciones de estudio
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Buenos Aires, Argentina
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Cordoba, Argentina
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Rosario, Argentina
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S.M. De Tucuman, Argentina
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San Miguel De Tucuman, Argentina
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Maroochydore, Australia
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Melbourne, Australia
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Wien, Austria
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Brussels, Bélgica
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Liege, Bélgica
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Manitoba
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Winnipeg, Manitoba, Canadá
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Newfoundland and Labrador
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St. John'S, Newfoundland and Labrador, Canadá
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Rancagua, Chile
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Santiago, Chile
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Daejeon, Corea, república de
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Incheon, Corea, república de
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Seoul, Corea, república de
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Suwon, Corea, república de
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Madrid, España
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Santander, España
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Sevilla, España
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Sevilla N/A, España
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Valencia, España
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Alabama
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Birmingham, Alabama, Estados Unidos
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Mobile, Alabama, Estados Unidos
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California
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Upland, California, Estados Unidos
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Florida
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Jacksonville, Florida, Estados Unidos
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Miami, Florida, Estados Unidos
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Idaho
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Coeur D'Alene, Idaho, Estados Unidos
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Illinois
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Moline, Illinois, Estados Unidos
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Springfield, Illinois, Estados Unidos
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Kansas
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Kansas City, Kansas, Estados Unidos
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Witchita, Kansas, Estados Unidos
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Minnesota
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Saint Paul, Minnesota, Estados Unidos
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Missouri
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Kansas City, Missouri, Estados Unidos
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Nebraska
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Lincoln, Nebraska, Estados Unidos
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North Carolina
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Charlotte, North Carolina, Estados Unidos
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Pennsylvania
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Duncansville, Pennsylvania, Estados Unidos
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Texas
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Dallas, Texas, Estados Unidos
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Fort Worth, Texas, Estados Unidos
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Lubbock, Texas, Estados Unidos
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Moscow, Federación Rusa
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Saratov, Federación Rusa
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Yaroslavl, Federación Rusa
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Cebu, Filipinas
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Manila, Filipinas
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Quezon, Filipinas
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Budapest, Hungría
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Gyula, Hungría
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Szombathely, Hungría
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Bangalore, India
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Lucknow Gpo, India
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Secunderabad, India
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Precinct 7, Malasia
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Saemban, Malasia
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Selayang N/A, Malasia
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Auckland, Nueva Zelanda
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Timaru, Nueva Zelanda
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Bialystok, Polonia
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Elblag, Polonia
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Kalisz, Polonia
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Szczecin, Polonia
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Warsaw, Polonia
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Leeds, Reino Unido
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London, Reino Unido
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Singapore, Singapur
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Bangkok, Tailandia
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Chiang Mai, Tailandia
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Kaohsiung, Taiwán
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Taichung, Taiwán
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Taipei, Taiwán
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Tiachung, Taiwán
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Dnipropetrovsk, Ucrania
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Donetsk, Ucrania
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Kharkiv, Ucrania
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Kiev, Ucrania
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Criterios de participación
Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.
Criterio de elegibilidad
Edades elegibles para estudiar
18 años y mayores (Adulto, Adulto Mayor)
Acepta Voluntarios Saludables
No
Géneros elegibles para el estudio
Todos
Descripción
Inclusion Criteria:
- Have a diagnosis of rheumatoid arthritis (RA) (according to the revised 1987 criteria of the ACR) for at least 3 months prior to first administration of study agent
- Are methotrexate (MTX)-naïve (ie, have not received more than 3 weekly doses of MTX for RA at any time)
- Have active RA as defined by persistent disease activity with at least 4 swollen and 4 tender joints, at the time of screening and baseline, and at least 2 of the following 4 criteria: a) C-reactive protein (CRP) >=1.5 mg/dL at screening or erythrocyte sedimentation rate (ESR) by Westergren method of >= 28 mm in the first hour at screening or baseline, b)Morning stiffness of >= 30 minutes at screening and baseline, c)Bone erosion by x-ray and/or MRI prior to first administration of study agent, d)Anti-cyclic citrullinated peptide (anti-CCP) antibody-positive or rheumatoid factor (RF) positive at screening
- If using oral corticosteroids, must be on a stable dose equivalent to <= 10 mg of prednisone/day for at least 2 weeks prior to first administration of study agent.
Exclusion Criteria:
- Can not have inflammatory diseases other than RA that might confound the evaluation of the benefit of golimumab therapy
- No treatment with disease-modifying anti-rheumatic drugs (DMARDs)/systemic immunosuppressives during the 4 weeks prior to the first administration of study agent
- No prior treatment with biologic anti-TNF drugs (infliximab, etanercept, adalimumab)
- No history of, or ongoing, chronic or recurrent infectious disease
- No serious infection within 2 months prior to first administration of study agent.
Plan de estudios
Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Cuadruplicar
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
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Experimental: Group 1: Placebo + Methotrexate
Placebo subcutaneous injections (SC) every 4 weeks from Week 0 for up to 5 years (unless early escape at week 28); Methotrexate - 10 to 20 mg weekly from Week 0 for up to 5 years; Golimumab - if early escape, 50 mg SC injections every 4 weeks from Week 28 up to 5 years; Golimumab - Dr's discretion after unblinding (in participants receiving methotrexate plus placebo), 50 mg SC injections every 4 weeks up to 5 years; Golimumab- Dr's discretion after unblinding, dose adjusted from 50 to 100 mg and from 100 to 50mg.
Duration of the blinded period will be until the week-52 database lock.
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SC injections
Methotrexate capsules will be filled with microcrystalline cellulose (Avicel PH 102) and a 2.5 mg methotrexate tablet.
SC injections
SC injections
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Experimental: Group 2: Golimumab 100 mg + Placebo
Golimumab 100 mg SC injections every 4 weeks from Week 0 for up to 5 years; placebo capsules weekly from Week 0 for up to 5 years (unless early escape at Week 28); Methotrexate - if early escape, 10 to 20 mg weekly from Week 28 up to 5 years; Methotrexate - Dr's discretion after unblinding (in participants receiving golimumab plus placebo) 10 to 20 mg weekly for up to 5 years; Golimumab - Dr's discretion after unblinding, dose adjusted from 100 to 50mg.
Duration of the blinded period will be until the week-52 database lock.
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Methotrexate capsules will be filled with microcrystalline cellulose (Avicel PH 102) and a 2.5 mg methotrexate tablet.
SC injections
SC injections
Placebo capsules will be filled with microcrystalline cellulose (Avicel PH 102).
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Experimental: Group 3: Golimumab 50 mg + Methotrexate
Golimumab 50 mg SC injections every 4 weeks from Week 0 for up to 5 years (unless early escape at week 28); Methotrexate - 10 to 20 mg weekly from Week 0 for up to 5 years; Golimumab - if early escape, 100 mg SC injections every 4 weeks from Week 28 for up to 5 yrs; Golimumab - Dr's discretion after unblinding, dose adjusted from 50 to 100 mg and from 100 to 50mg.
Duration of the blinded period will be until the week-52 database lock.
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Methotrexate capsules will be filled with microcrystalline cellulose (Avicel PH 102) and a 2.5 mg methotrexate tablet.
SC injections
SC injections
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Experimental: Group 4: Golimumab 100 mg + Methotrexate
Golimumab 100 mg SC injections every 4 weeks from Week 0 for up to 5 years; Methotrexate - 10 to 20 mg weekly from Week 0 for up to 5 years; Golimumab - Dr's discretion after unblinding, dose adjusted from 100 to 50mg.
Duration of the blinded period will be until the week-52 database lock.
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Methotrexate capsules will be filled with microcrystalline cellulose (Avicel PH 102) and a 2.5 mg methotrexate tablet.
SC injections
SC injections
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Number of Participants Who Achieved American College of Rheumatology (ACR) 50 Response at Week 24
Periodo de tiempo: Week 24
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ACR 50 response is defined as a greater than or equal to 50 percent improvement from baseline in: 1. Swollen joint count (66 joints) and tender joint count (68 joints) 2. greater than or equal to 50 percentage improvement in 3 of the following 5 assessments: a. Patient's assessment of pain by the Visual Analogue Scale (VAS) (0-10 cm) b.Patient's Global Assessment of Disease activity VAS (0-10 cm) c.
Physician's Global Assessment of Disease Activity VAS (0-10 cm) d.
Patient's assessment of physical function as measured by the Health Assessment Questionnaire (HAQ) e. C reactive protein.
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Week 24
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Change From Baseline in Total Van Der Heijde Modified Sharp (vdH-S) Score at Week 52
Periodo de tiempo: Baseline and Week 52
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The vdH-S score is the sum of the joint erosion score and the joint-space narrowing (JSN) score.
The total score ranges from 0 (best) to 448 (worst) with higher scores indicating more joint damage.
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Baseline and Week 52
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Number of Participants Who Achieved American College of Rheumatology (ACR) 20 Response at Week 24
Periodo de tiempo: Week 24
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ACR 20 response is defined as a greater than or equal to 20 percent improvement from baseline in: 1. Swollen joint count (66 joints) and tender joint count (68 joints) 2. greater than or equal to 20 percentage improvement in 3 of the following 5 assessments: a. Patient's assessment of pain by the Visual Analogue Scale (VAS) (0-10 cm) b.Patient's Global Assessment of Disease activity VAS (0-10 cm) c.
Physician's Global Assessment of Disease Activity VAS (0-10 cm) d.
Patient's assessment of physical function as measured by the Health Assessment Questionnaire (HAQ) e. C reactive protein.
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Week 24
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Number of Patients With Abnormal Baseline C-reactive Protein (CRP) Who Achieved American College of Rheumatology (ACR) 50 Response at Week 24
Periodo de tiempo: Week 24
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ACR 50 response is defined as a greater than or equal to 50 percent improvement from baseline in: 1. Swollen joint count (66 joints) and tender joint count (68 joints) 2. greater than or equal to 50 percentage improvement in 3 of the following 5 assessments: a. Patient's assessment of pain by the Visual Analogue Scale (VAS) (0-10 cm) b.Patient's Global Assessment of Disease activity VAS (0-10 cm) c.
Physician's Global Assessment of Disease Activity VAS (0-10 cm) d.
Patient's assessment of physical function as measured by the Health Assessment Questionnaire (HAQ) e. C reactive protein.
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Week 24
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Change From Baseline in Total Van Der Heijde Modified Sharp (vdH-S) Score at Week 52 in Patients With Abnormal C-reactive Protein (CRP Greater Than 1.0 mg/dL) at Baseline
Periodo de tiempo: Baseline and Week 52
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The vdH-S score is the sum of the joint erosion score and the joint-space narrowing (JSN) score.
The total score ranges from 0 (best) to 448 (worst) with higher scores indicating more joint damage.
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Baseline and Week 52
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Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Patrocinador
Colaboradores
Publicaciones y enlaces útiles
La persona responsable de ingresar información sobre el estudio proporciona voluntariamente estas publicaciones. Estos pueden ser sobre cualquier cosa relacionada con el estudio.
Publicaciones Generales
- Kay J, Fleischmann R, Keystone E, Hsia EC, Hsu B, Zhou Y, Goldstein N, Braun J. Five-year Safety Data from 5 Clinical Trials of Subcutaneous Golimumab in Patients with Rheumatoid Arthritis, Psoriatic Arthritis, and Ankylosing Spondylitis. J Rheumatol. 2016 Dec;43(12):2120-2130. doi: 10.3899/jrheum.160420. Epub 2016 Nov 1.
- Baker JF, Conaghan PG, Emery P, Baker DG, Ostergaard M. Relationship of patient-reported outcomes with MRI measures in rheumatoid arthritis. Ann Rheum Dis. 2017 Mar;76(3):486-490. doi: 10.1136/annrheumdis-2016-209463. Epub 2016 Jul 18.
- Emery P, Fleischmann RM, Hsia EC, Xu S, Zhou Y, Baker D. Efficacy of golimumab plus methotrexate in methotrexate-naive patients with severe active rheumatoid arthritis. Clin Rheumatol. 2014 Sep;33(9):1239-46. doi: 10.1007/s10067-014-2731-y. Epub 2014 Jul 9.
- Emery P, Fleischmann RM, Doyle MK, Strusberg I, Durez P, Nash P, Amante E, Churchill M, Park W, Pons-Estel B, Xu W, Xu S, Wu Z, Hsia EC. Golimumab, a human anti-tumor necrosis factor monoclonal antibody, injected subcutaneously every 4 weeks in patients with active rheumatoid arthritis who had never taken methotrexate: 1-year and 2-year clinical, radiologic, and physical function findings of a phase III, multicenter, randomized, double-blind, placebo-controlled study. Arthritis Care Res (Hoboken). 2013 Nov;65(11):1732-42. doi: 10.1002/acr.22072.
- Ostergaard M, Emery P, Conaghan PG, Fleischmann R, Hsia EC, Xu W, Rahman MU. Significant improvement in synovitis, osteitis, and bone erosion following golimumab and methotrexate combination therapy as compared with methotrexate alone: a magnetic resonance imaging study of 318 methotrexate-naive rheumatoid arthritis patients. Arthritis Rheum. 2011 Dec;63(12):3712-22. doi: 10.1002/art.30592.
Fechas de registro del estudio
Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.
Fechas importantes del estudio
Inicio del estudio
1 de diciembre de 2005
Finalización primaria (Actual)
1 de abril de 2008
Finalización del estudio (Actual)
1 de junio de 2012
Fechas de registro del estudio
Enviado por primera vez
11 de diciembre de 2005
Primero enviado que cumplió con los criterios de control de calidad
11 de diciembre de 2005
Publicado por primera vez (Estimar)
13 de diciembre de 2005
Actualizaciones de registros de estudio
Última actualización publicada (Estimar)
5 de septiembre de 2014
Última actualización enviada que cumplió con los criterios de control de calidad
27 de agosto de 2014
Última verificación
1 de agosto de 2014
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
- Enfermedades del sistema inmunológico
- Enfermedades autoinmunes
- Enfermedades Articulares
- Enfermedades musculoesqueléticas
- Enfermedades reumáticas
- Enfermedades del tejido conectivo
- Artritis
- Artritis Reumatoide
- Efectos fisiológicos de las drogas
- Mecanismos moleculares de acción farmacológica
- Inhibidores de la síntesis de ácidos nucleicos
- Inhibidores de enzimas
- Agentes antiinflamatorios
- Agentes antirreumáticos
- Antimetabolitos, Antineoplásicos
- Antimetabolitos
- Agentes antineoplásicos
- Agentes inmunosupresores
- Factores inmunológicos
- Agentes dermatológicos
- Agentes de control reproductivo
- Agentes abortivos, no esteroideos
- Agentes abortivos
- Antagonistas del ácido fólico
- Inhibidores del factor de necrosis tumoral
- Anticuerpos Monoclonales
- Metotrexato
- Golimumab
Otros números de identificación del estudio
- CR006331
- GO-BEFORE
- C0524T05
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .