- ICH GCP
- Registro de ensayos clínicos de EE. UU.
- Ensayo clínico NCT02321930
Musculoskeletal Ultrasound Assessment of Therapeutic Response of Tofacitinib in Rheumatoid Arthritis Patients
27 de febrero de 2019 actualizado por: Dr. Veena Ranganath, University of California, Los Angeles
This proposal will evaluate if musculoskeletal ultrasound (MSUS) measures or multi-biomarker disease activity (MBDA) improve in patients treated with tofacitinib over 3 months, and whether early MSUS measures/MBDA can predict response to therapy.
Descripción general del estudio
Estado
Terminado
Condiciones
Intervención / Tratamiento
Descripción detallada
This is a pilot open-label trial of 25 RA patients treated with tofacitinib over 3 months.
The patients meeting inclusion criteria will be started on tofacitinib 5mg po bid.
Patients will be recruited from the UCLA Rheumatology Clinics.
Inclusion criteria will include the following: meeting ACR 1987 RA criteria, DAS28≥3.2, age≥18, and PDUS>10 (see below for more details).
Patients who are deemed unsafe to enroll will be excluded.
Ultrasound measures (PDUS/GSUS) and MBDA scores will be obtained at screen, baseline, 2 weeks, and 3 months.
In addition, we will also obtain HAQ-DI, CDAI, and DAS28 at the same time points.
In addition, we will have a 6 week visit for capturing adverse events, concomitant drugs, drug dispensation, and evaluation of adherence.
Currently, there are several US measures to evaluate therapeutic response in RA patients that have been used in the literature.
Some US studies evaluate all joints involved in RA, which is time consuming.
At present, there is no consensus as to the ideal ultrasound scoring system.
However, we will utilize a 34-joint US scoring system to evaluate response to therapy in this proposal (see Table 1).
Our research team has expertise in MSUS (given several workshops/lectures nationally) and we have proficiency in designing/conducting MSUS clinical trials.
We currently have 4 ultrasonography-rheumatologists at UCLA who are ACR certified in MSUS.
Tipo de estudio
Intervencionista
Inscripción (Actual)
37
Fase
- Fase 4
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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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
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:
- Patient must meet 1987 ACR criteria
- Age > 18 years of age
- Baseline DAS28/ESR>=3.2
- Stable concomitant DMARDs
- Stable prednisone <10mg or equivalent
- Power Doppler score of >=10
- Female subjects of childbearing potential must test negative for pregnancy
- Male and female subjects of childbearing potential must agree to use contraception throughout the study
- Negative QuantiFERON Gold test at screening
Exclusion Criteria:
- No active TB
- Prednisone >10 mg
- Pregnancy or breast feeding
- Prior treatment with tofacitinib
- Concomitant biologic therapy (TNF inhibitors, IL-6 inhibitors, etc.)
- Active infection with HIV, hepatitis B or C, or herpes zoster
Subjects with any uncontrolled clinically significant laboratory abnormality or any of the following laboratory abnormalities:
- Evidence of hematopoietic disorder or hemoglobin <9 g/dL
- Absolute lymphocyte count <0.75 x 109/L (<750/mm3)
- Absolute neutrophil count <1.2 x 109/L (<1200/mm3)
- Platelet count <100 x 109/L (<100,000/mm3)
- Alanine aminotransferase (ALT), or aspartate aminotransferase (AST) >1.5 times the upper limit of normal (x ULN)
- Estimated GFR <40 ml/min
- Subjects who have received live or live attenuated vaccines within 6 weeks prior to the first dose of study drug (or the zoster vaccine)
- Subjects who require concomitant treatment with medications that are potent inhibitors of cytochrome P450 3A4 (CYP3A4), both moderate inhibitors of CYP3A4 and potent inhibitors of CYP2C19, and potent CYP inducers (See Appendix)
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: N / A
- Modelo Intervencionista: Asignación de un solo grupo
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
---|---|
Otro: tofacitinib 5mg po bid
Open label with tofacitinib 5mg po bid
|
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
---|---|---|
PDUS
Periodo de tiempo: Baseline, Week 2, Month 3
|
30 joints will be evaluated using a 0 to 3 point scale for each joint and the sum of these represents PDUS.
The Power Doppler Synovitis Score (PDUS) ranges from 0 to 90.
Scores of 0 indicate the least amount of inflammation of the joint while scores of 3 indicate the most amount of inflammation.
A higher value of the total score for PDUS represents more severe disease level.
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Baseline, Week 2, Month 3
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GSUS
Periodo de tiempo: Baseline, Week 2, Month 3
|
30 joints will be evaluated using a 0 to 3 point scale for each joint and the sum of these represents GSUS.
The grey scale synovial hypertrophy score (GSUS) ranges from 0 to 90.
Scores of 0 indicate the least amount of inflammation of the joint while scores of 3 indicate the most amount of inflammation.
A higher value of the total score for GSUS represents more severe disease level.
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Baseline, Week 2, Month 3
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CDAI
Periodo de tiempo: Baseline, Week 2, Month 3
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CDAI was derived as the sum of the following: tender joint count (TJC), swollen joint count (SJC), participant global assessment (PGA) of disease activity, and physician assessment of disease activity.
TJC and SJC were taken as the number of tender and swollen joints, respectively, out of 28 assessed joints.
PGA and physician assessment of disease activity were scored 0-100 millimeters (mm) and rounded to the nearest centimeter (cm) on a visual analog scale (VAS), where higher scores indicate greater perceived disease activity.
The total CDAI score range was 0-76, where higher scores indicate increased disease activity.
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Baseline, Week 2, Month 3
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DAS28/ESR
Periodo de tiempo: Baseline, Week 2, Month 3
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TJC and SJC were taken as the number of tender and swollen joints, respectively, out of 28 assessed joints.
Patient Global Assessment of disease activity was scored 0-100 millimeters (mm) and rounded to the nearest centimeter (cm) on a visual analog scale (VAS), where higher scores indicate greater perceived disease activity.
ESR lab value were included in the total calculation.
The scale being used is called the Disease Activity Score for 28 Joints (DAS28) using the Erythrocyte Sedimentation Rate (ESR) in the calculation.The scale ranges from 0 to 9.4, where higher values represent a higher disease activity.The complete formula to calculate DAS28/ESR is 0.56*sqrt(TJC) + (0.28*sqrt(SJC)) + (0.7*ln(ESR)) + (0.014*Patient Global*10).
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Baseline, Week 2, Month 3
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
---|---|---|
MBDA
Periodo de tiempo: Baseline, Week 2, Month 3
|
The multi-biomarker disease activity (MBDA) blood test assesses RA disease activity.
An algorithm of 12 markers is used to characterize RA disease activity on a scale of 1-100, where a score of 100 represents the highest level of disease activity present.
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Baseline, Week 2, Month 3
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Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Patrocinador
Investigadores
- Investigador principal: Veena Ranganath, MD, MS, UCLA David Geffen School of Medicine, Division of Rheumatology
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
- 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.
- Kim SK, Jung UH, Kim JW, Choe JY. The beneficial effect of baricitinib on ultrasound-detected synovial inflammation and bone damage in rheumatoid arthritis: Preliminarily data from single center-based observational study for 24 weeks. Medicine (Baltimore). 2021 Jul 30;100(30):e26739. doi: 10.1097/MD.0000000000026739.
- Razmjou AA, Brook J, Elashoff D, Kaeley G, Choi S, Kermani T, Ranganath VK. Ultrasound and multi-biomarker disease activity score for assessing and predicting clinical response to tofacitinib treatment in patients with rheumatoid arthritis. BMC Rheumatol. 2020 Oct 19;4:55. doi: 10.1186/s41927-020-00153-4. eCollection 2020.
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
16 de febrero de 2016
Finalización primaria (Actual)
29 de septiembre de 2017
Finalización del estudio (Actual)
29 de septiembre de 2017
Fechas de registro del estudio
Enviado por primera vez
23 de septiembre de 2014
Primero enviado que cumplió con los criterios de control de calidad
16 de diciembre de 2014
Publicado por primera vez (Estimar)
22 de diciembre de 2014
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
19 de marzo de 2019
Última actualización enviada que cumplió con los criterios de control de calidad
27 de febrero de 2019
Última verificación
1 de febrero de 2019
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
- Mecanismos moleculares de acción farmacológica
- Inhibidores de enzimas
- Inhibidores de la proteína quinasa
- Tofacitinib
Otros números de identificación del estudio
- WI193025
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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