- ICH GCP
- Registro de ensayos clínicos de EE. UU.
- Ensayo clínico NCT01717859
Musculoskeletal Ultrasound in Predicting Early Dose Titration With Tocilizumab (RASTS)
Descripción general del estudio
Descripción detallada
Tipo de estudio
Inscripción (Actual)
Fase
- Fase 4
Contactos y Ubicaciones
Ubicaciones de estudio
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California
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Los Angeles, California, Estados Unidos, 90095
- UCLA David Geffen School of Medicine, Division of Rheumatology
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
Inclusion Criteria
Patients must have rheumatoid arthritis. Patients will be included in the trial based on the following criteria:
- Patient must meet 1987 American College of Rheumatology (ACR) criteria,
- Age > 18 years of age,
- Baseline DAS28/ESR>4.4,
Stable concomitant DMARDs for more than 1 month (methotrexate, leflunomide, plaquenil, sulfasalazine, or no DMARDs). However, if the patient is not on DMARD, history of DMARD use required.
- If not on DMARD (and the patient satisfies the above statement), the patient can opt for monotherapy with tocilizumab or combination therapy OR
- If on biologic monotherapy, can opt for monotherapy with tocilizumab or DMARD combination therapy (ie. patients cannot be on biologic with TCZ)
6) Power Doppler score of >10 at screening.
General Medical Concerns:
- Normal organ function, except if abnormal due to the disease under investigation
- Men and women of reproductive potential must agree to use an acceptable method of birth control during treatment and for six months after completion of treatment.
- Subject has provided written informed consent.
Exclusion Criteria
A patient will be excluded if the answer to any of the following statements is "yes".
General:
Major surgery (including joint surgery) within 8 weeks prior to baseline or planned major surgery within 6 months after baseline.
Excluded Previous or Concomitant Therapy:
- Treatment with any investigational agent within 4 weeks (or 5 half-lives of the investigational drug, whichever is longer) of baseline.
- Previous treatment with any cell-depleting therapies, including investigational agents or approved therapies, some examples are CAMPATH, anti-CD4, anti-CD5, anti-CD3.
- Previous treatment with anti-CD19 and anti-CD20 within 6 months of start of the study.
- Treatment with intravenous gamma globulin, plasmapheresis or Prosorba column within 6 months of baseline.
- Immunization with a live/attenuated vaccine within 4 weeks prior to baseline.
- Previous treatment with TCZ.
- Any previous treatment with alkylating agents such as chlorambucil, or with total lymphoid irradiation.
Use of prednisone > 10mg at baseline.
Exclusions for General Safety:
- History of severe allergic or anaphylactic reactions to human, humanized or murine monoclonal antibodies.
- Evidence of serious uncontrolled concomitant cardiovascular, nervous system, pulmonary (including obstructive pulmonary disease), renal, hepatic, endocrine (include uncontrolled diabetes mellitus) or gastrointestinal disease (including complicated diverticulitis, ulcerative colitis, or Crohn's disease.)
- Current liver disease as determined by principal investigator unless related to primary disease under investigation
- Known active current or history of recurrent bacterial, viral, fungal, mycobacterial or other infections (including but not limited to tuberculosis and atypical mycobacterial disease, Hepatitis B and C, and herpes zoster, but excluding fungal infections of nail beds).
- Any major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks of baseline or oral antibiotics within 2 weeks prior to baseline.
- Active Tuberculosis (TB) requiring treatment within the previous 3 years. Patients should be screened for latent TB and, if positive, treated following local practice guidelines prior to initiating TCZ. Patients treated for tuberculosis with no recurrence in 3 years are permitted.
- Primary or secondary immunodeficiency (history of or currently active) unless related to primary disease under investigation.
- Evidence of active malignant disease, malignancies diagnosed within the previous 5 years (including hematological malignancies and solid tumors, except basal and squamous cell carcinoma of the skin or carcinoma in situ of the cervix uteri that has been excised and cured), or breast cancer diagnosed within the previous 5 years.
- Pregnant women or nursing (breast feeding) mothers.
- Patients with reproductive potential not willing to use an effective method of contraception.
- History of alcohol, drug or chemical abuse within 1 year prior to screening.
- Neuropathies or other conditions that might interfere with pain evaluation unless related to primary disease under investigation.
- Patients with lack of peripheral venous access.
Body weight of > 150 kg.
Laboratory Exclusion criteria (at screening):
- Serum creatinine > 1.6 mg/dL (141 µmol/L) in female patients and > 1.9 mg/dL (168 µmol/L) in male patients. Patients with serum creatinine values exceeding limits may be eligible for the study if their estimated glomerular filtration rates (GFR) are >30.
- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 1.5 times upper limit of normal (ULN)
- Total Bilirubin > ULN
- Platelet count < 100 x 109/L (100,000/mm3)
- Hemoglobin < 85 g/L (8.5 g/dL; 5.3 mmol/L)
- White Blood Cells < 3.0 x 109/L (3000/mm3)
- Absolute Neutrophil Count < 2.0 x 109/L (2000/mm3)
- Absolute Lymphocyte Count < 0.5 x 109/L (500/mm3)
- Positive Hepatitis BsAg, or Hepatitis C antibody
- HIV positive
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Otro
- Asignación: N / A
- Modelo Intervencionista: Asignación de un solo grupo
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
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Otro: Tocilizumab
All subjects will receive tocilizumab.
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All subjects will start at 4mg/kg.
After 3 months, if DAS28 > 3.2, dosage will be escalated to 8 mg/kg.
Otros nombres:
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Baseline to Month 3 Change in Total Power Doppler Synovitis Score of 34 Joints (Range 0 - 102)
Periodo de tiempo: Baseline, 3 Month
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34 joints will be evaluated using a 0 to 3 point scale for each joint. Power Doppler synovitis score is the sum of all the joint scores. Change scores are calculated by subtracting Baseline minus 3 Month Power Doppler scores. This scale is called the Power Doppler Synovitis Score (PDUS). It ranges from 0 to 102. Scores of 0 indicate the least amount of inflammation of the joint while scores of 3 indicate the most amount of inflammation. Therefore, a higher value of the total score for PDUS represents more severe disease level. |
Baseline, 3 Month
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
---|---|---|
Baseline to Month 6 Change in Total Power Doppler Synovitis Score of 34 Joints (Range 0 - 102)
Periodo de tiempo: Baseline, 6 Month
|
34 joints will be evaluated using a 0 to 3 point scale for each joint. Power Doppler synovitis score is the sum of all the joint scores. Change scores are calculated by subtracting Baseline minus 6 Month Power Doppler scores. This scale is called the Power Doppler Synovitis Score (PDUS). It ranges from 0 to 102. Scores of 0 indicate the least amount of inflammation of the joint while scores of 3 indicate the most amount of inflammation. Therefore, a higher value of the total score for PDUS represents more severe disease level. |
Baseline, 6 Month
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Baseline to Month 3 Change in Total B-mode Synovial Hypertrophy Score of 34 Joints
Periodo de tiempo: Baseline, 3 Month
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34 joints will be evaluated using a 0 to 3 point scale for each joint. Synovial hypertrophy score is the sum of all the joint scores. Change scores are calculated by subtracting Baseline minus 3 Month Synovial Hypertrophy Scores. This scale is called the Grey Scale Synovial Hypertrophy Score (GSUS). Please note that B-mode is the same as GSUS. It ranges from 0 to 102. Scores of 0 indicate the least amount of inflammation of the joint while scores of 3 indicate the most amount of inflammation. Therefore, a higher value of the total score for GSUS represents more severe disease level. |
Baseline, 3 Month
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Baseline to Month 6 Change in Total B-mode Synovial Hypertrophy Score of 34 Joints
Periodo de tiempo: Baseline, 6 Month
|
34 joints will be evaluated using a 0 to 3 point scale for each joint. Synovial hypertrophy score is the sum of all the joint scores. Change scores are calculated by subtracting Baseline minus 6 Month Synovial Hypertrophy Scores. This scale is called the Grey Scale Synovial Hypertrophy Score (GSUS). Please note that B-mode is the same as GSUS. It ranges from 0 to 102. Scores of 0 indicate the least amount of inflammation of the joint while scores of 3 indicate the most amount of inflammation. Therefore, a higher value of the total score for GSUS represents more severe disease level. |
Baseline, 6 Month
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Baseline to Month 3 Change in DAS28/ESR
Periodo de tiempo: Baseline, 3 month
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28 joints will be evaluated for Tender Joint Count (TJC) and Swollen Joint Count (SJC) as well as patient and physician global values assessed at the time of each visit, finally the ESR lab value will be included in the total calculation. Change scores are calculated by subtracting Baseline minus 3 Month Disease Activity Score (DAS) scores. The scale being used is called the Disease Activity Score for 28 Joints (DAS28) using the Erythrocyte Sedimentation Rate (ESR) in the calculation rather than the C Reactive Protein (CRP). The scale ranges from 0 to 9.4. Values of DAS28 below 2.6 imply remission, below 3.2 imply low disease activity and greater than 5.1 implies active disease. |
Baseline, 3 month
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Baseline to Month 6 Change in DAS28/ESR
Periodo de tiempo: Baseline, 6 Month
|
28 joints will be evaluated for TJC and SJC as well as patient and physician global values assessed at the time of each visit, finally the ESR lab value will be included in the total calculation. Change scores are calculated by subtracting Baseline minus 6 Month DAS scores. The scale being used is called the Disease Activity Score for 28 Joints (DAS28) using the Erythrocyte Sedimentation Rate (ESR) in the calculation rather than the C Reactive Protein (CRP). The scale ranges from 0 to 9.4. Values of DAS28 below 2.6 imply remission, below 3.2 imply low disease activity and greater than 5.1 implies active disease. |
Baseline, 6 Month
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Baseline to Month 3 Change in CDAI
Periodo de tiempo: Baseline, 3 month
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28 joints will be evaluated for TJC and SJC as well as patient and physician global values assessed at the time of each visit. Change scores are calculated by subtracting Baseline minus 3 Month CDAI scores. The scale being used is called the Clinical Disease Activity Index (CDAI) and has a range of 0 to 76. Values of CDAI below 2.8 imply remission, below 10 imply low disease activity, below 22 imply moderate disease activity, and above 22 implies high disease activity. |
Baseline, 3 month
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Baseline to Month 6 Change in CDAI
Periodo de tiempo: Baseline, 6 Month
|
28 joints will be evaluated for TJC and SJC as well as patient and physician global values assessed at the time of each visit. Change scores are calculated by subtracting Baseline minus 6 Month CDAI scores. The scale being used is called the Clinical Disease Activity Index (CDAI) and has a range of 0 to 76. Values of CDAI below 2.8 imply remission, below 10 imply low disease activity, below 22 imply moderate disease activity, and above 22 implies high disease activity. |
Baseline, 6 Month
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Colaboradores e Investigadores
Patrocinador
Colaboradores
Investigadores
- Investigador principal: Veena Ranganath, MD, MS, UCLA David Geffen School of Medicine, Division of Rheumatology
Publicaciones y enlaces útiles
Publicaciones Generales
- Morris NT, Brook J, Ben-Artzi A, Martin W, Kermani TA, Avedikian-Tatosyan L, Karpouzas G, Nagam H, Navarro G, Choi S, Taylor MB, Elashoff D, Kaeley GS, Ranganath VK. Doppler ultrasound impacts response to intravenous tocilizumab in rheumatoid arthritis patients. Clin Rheumatol. 2021 Dec;40(12):5055-5065. doi: 10.1007/s10067-021-05857-7. Epub 2021 Jul 16.
- Kuo D, Morris NT, Kaeley GS, Ben-Artzi A, Brook J, Elashoff DA, Ranganath VK. Sentinel joint scoring in rheumatoid arthritis: an individualized power Doppler assessment strategy. Clin Rheumatol. 2021 Mar;40(3):1077-1084. doi: 10.1007/s10067-020-05340-9. Epub 2020 Aug 15.
- Choate EA, Kaeley GS, Brook J, Altman RD, FitzGerald JD, Floegel-Shetty AR, Elashoff DA, Ranganath VK. Ultrasound detects synovitis in replaced and other surgically operated joints in rheumatoid arthritis patients. BMC Rheumatol. 2020 Feb 3;4:8. doi: 10.1186/s41927-019-0107-2. eCollection 2020.
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio
Finalización primaria (Actual)
Finalización del estudio (Actual)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Estimar)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- ML28542 (Otro identificador: Genentech Inc.)
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. .
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CelltrionAún no reclutando
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Fundacion SEIMC-GESIDARoche Pharma AG; Dynamic Science S.L.Terminado
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Hoffmann-La RocheTerminado
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University of OklahomaHoffmann-La RocheYa no está disponibleArtritis reumatoide juvenil idiopáticaEstados Unidos
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University of ChicagoReclutamiento
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Reade Rheumatology Research InstituteZonMw: The Netherlands Organisation for Health Research and DevelopmentReclutamientoArtritis ReumatoidePaíses Bajos