Study Comparing the Safety and Efficacy of Belatacept With That of Cyclosporine in Patients With a Transplanted Kidney
27 de noviembre de 2013 actualizado por: Bristol-Myers Squibb
Phase II/III, Open-Label, Randomized, Controlled, Multiple-Dose Study of Efficacy and Safety of BMS-224818 (Belatacept) as Part of a Quadruple Drug Regimen in First Renal Transplant Recipients
The purpose of this study is to determine whether treatment with Belatacept (BMS-224818) is as efficacious as treatment with cyclosporine at preventing acute rejection and with a superior safety/tolerability profile (better kidney function and blood pressure, fewer lipid problems, less diabetes mellitus).
Descripción general del estudio
Estado
Terminado
Condiciones
Intervención / Tratamiento
Tipo de estudio
Intervencionista
Inscripción (Actual)
230
Fase
- Fase 2
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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San Francisco, California, Estados Unidos, 94143-0001
- Univ. of Calif. - San Francisco
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Georgia
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Atlanta, Georgia, Estados Unidos, 30322
- Emory Univ. School of Medicine
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Maryland
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Baltimore, Maryland, Estados Unidos, 21205
- Johns Hopkins University
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Massachusetts
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Boston, Massachusetts, Estados Unidos, 02114
- Massachusetts General Hospital
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Minnesota
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Rochester, Minnesota, Estados Unidos, 55905
- Mayo Clinic
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Nebraska
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Omaha, Nebraska, Estados Unidos, 68198-1002
- Univ. of Nebraska Medical Center
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New Jersey
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Livingston, New Jersey, Estados Unidos, 07039
- Saint Barnabas Medical Center
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New York
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New York, New York, Estados Unidos, 10029-6574
- Mount Sinai Medical Center
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Pennsylvania
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Philadelphia, Pennsylvania, Estados Unidos, 19104
- Univ. of Pennsylvania
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South Carolina
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Charleston, South Carolina, Estados Unidos, 29425
- Medical Univ. of South Carolina
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Texas
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Dallas, Texas, Estados Unidos, 75246
- Baylor Univ. Medical Center
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Wisconsin
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Madison, Wisconsin, Estados Unidos, 53792-7375
- Univ. of Wisconsin
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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
Key inclusion criteria
- Recipients of first kidney transplant
Key exclusion criteria
- Those at high risk for acute allograft rejection, including those who receive a second or more renal transplant, those with a history of panel reactive antibody levels >20%, and those considered by investigators to be at relatively higher risk for acute rejection
- Human leukocyte antigen-identical donor-recipient pairs
- Cold ischemia time >36 hours (donor kidney)
- Participants who are positive for hepatitis C antibody, on polymerase chain reaction, for hepatitis B surface antigen, and for human immunodeficiency virus
- A positive purified protein derivative tuberculosis test (test performed within 1 year of enrollment), unless previously vaccinated with Bacille-Calmette-Guérin or those who had a history of adequate chemoprophylaxis
- Any active infection that would normally exclude transplantation
- Recipients of multiple organ transplants
- Donor age >60 or <6 years or donors whose hearts were not beating
- Recipients with underlying renal disease of (due to risk of rapid disease recurrence in the allograft): focal segmental glomerulosclerosis, Type I or II membranoproliferative glomerulonephritis, or hemolytic uremic syndrome/ thrombotic thrombocytopenic purpura
- A positive T-cell lymphocytoxic crossmatch using donor lymphocytes and recipient serum
- A history of true allergy to intravenous iodinated roentgenographic contrast agents
- Participants with life expectancy severely limited by disease state or other underlying medical condition
- A history of cancer (other than nonmelanoma skin cell cancers cured by local resection) within the last 5 years
- Mammogram film with any clinically significant abnormality requiring further investigation or biopsies
- History of substance abuse (drug or alcohol) or psychotic disorders that were not compatible with adequate study follow-up
- A currently functioning, nonrenal transplant
- Previous treatment with basiliximab for any reason
- Active peptic ulcer disease, chronic diarrhea, or gastrointestinal malabsorption
- Those who had used any investigational drug within 30 days before the Day 1 visit.
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: Prevención
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
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Experimental: Belatacept: More intensive (MI) regimen
The MI regimen was designed to achieve projected serum trough concentrations of belatacept of approximately 20 μg/mL through Day 99, and approximately 5 μg/mL through Day 183 (10 mg/kg on Days 1, 5, 15, 29, 43, 57, 71, 85, 113, 141, and 169).
After Day 169, patients were reallocated and dosed to achieve projected trough serum concentrations of approximately 2 or 0.25 μg/mL (5 mg/kg every 4 or 8 weeks starting on Day 197).
Those patients who received belatacept every 8 weeks received placebo infusions on scheduled treatment dates between infusions of active drug to maintain the blind between treatment regimens.
Patients initially received mycophenolate mofetil (MMF), 2 g/d orally, unless the investigator chose to administer ≥1 doses intravenously The first MMF dose was administered preoperatively; subsequent doses were administered in 2 or 3 divided doses, every 8-12 hours, beginning as soon as the patient was able to tolerate medications by mouth.
Corticosteroids given daily.
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Solution, intravenous
Otros nombres:
Oral, capsule
Corticosteroids given daily, orally or intravenously (IV).
Day of transplant (Day 1): methylprednisolone, 500 mg, given IV on arrival in operating room; Day 2: methylprednisolone, 250 mg, given IV once daily; Day 3: prednisone, 100 mg, given orally once daily; Day 4: prednisone, 50 mg, given orally once daily; Days 5 through 30: prednisone, 25 mg, given orally once daily; Days 31-44: prednisone, 22.5 mg, given orally once daily; Days 45-58: prednisone, 20 mg, given orally once daily
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Experimental: Belatacept: Less intensive (LI) regimen
The LI regimen was designed to achieve projected trough serum concentrations of belatacept of approximately 20 μg/mL through Day 29, and approximately 5 μg/mL through Day 99 (10 mg/kg on Days 1, 15, 29, 57 and 85).
After Day 85, these subjects were reallocated and dosed to achieve projected trough serum concentrations of either approximately 2 or 0.25 μg/mL (5 mg/kg every 4 or 8 weeks starting on Day 113).
Participants initially received mycophenolate mofetil (MMF), 2 g/d orally, unless the investigator chose to administer ≥1 doses intravenously The first MMF dose was administered preoperatively; subsequent doses were administered in 2 or 3 divided doses, every 8-12 hours, beginning as soon as the participant was able to tolerate medications by mouth.
Corticosteroids given daily.
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Solution, intravenous
Otros nombres:
Oral, capsule
Corticosteroids given daily, orally or intravenously (IV).
Day of transplant (Day 1): methylprednisolone, 500 mg, given IV on arrival in operating room; Day 2: methylprednisolone, 250 mg, given IV once daily; Day 3: prednisone, 100 mg, given orally once daily; Day 4: prednisone, 50 mg, given orally once daily; Days 5 through 30: prednisone, 25 mg, given orally once daily; Days 31-44: prednisone, 22.5 mg, given orally once daily; Days 45-58: prednisone, 20 mg, given orally once daily
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Experimental: Cyclosporine regimen
The initial daily dose was 7±3 mg/kg.
Subsequent doses were adjusted to maintain a predefined range of serum concentrations: 1st month, target level 150-400 ng/mL; after 1st month, target level of 150-300 ng/mL.
Participants initially received mycophenolate mofetil (MMF), 2 g/d orally, unless the investigator chose to administer ≥1 doses intravenously The first MMF dose was administered preoperatively; subsequent doses were administered in 2 or 3 divided doses, every 8-12 hours, beginning as soon as the participant was able to tolerate medications by mouth.
Corticosteroids given daily.
|
Oral, capsule
Corticosteroids given daily, orally or intravenously (IV).
Day of transplant (Day 1): methylprednisolone, 500 mg, given IV on arrival in operating room; Day 2: methylprednisolone, 250 mg, given IV once daily; Day 3: prednisone, 100 mg, given orally once daily; Day 4: prednisone, 50 mg, given orally once daily; Days 5 through 30: prednisone, 25 mg, given orally once daily; Days 31-44: prednisone, 22.5 mg, given orally once daily; Days 45-58: prednisone, 20 mg, given orally once daily
Oral, capsule
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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Number of Participants With an Episode of Clinically-suspected and Biopsy-proven Acute Rejection (CSPAR)
Periodo de tiempo: By Month 6 posttransplant (From Day 1 to Month 6)
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No participant was to receive treatment for acute rejection without a biopsy to confirm the diagnosis.
CSPAR=Clinically-suspected rejection, defined as an increase in serum creatinine ≥0.5 mg/dL compared with the baseline value in the absence of other factors known to adversely affect renal function, and biopsy-proven rejection, which includes all cases in which a biopsy was read by the central pathologist as demonstrating acute rejection regardless of the reason why the biopsy was performed.
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By Month 6 posttransplant (From Day 1 to Month 6)
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Percentage of Participants With Biopsy-proven Acute Rejection (BPAR) Through Months 6 and 12
Periodo de tiempo: Through Months 6 and 12 posttransplant (From Day 1 to Months 6 and 12)
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BPAR includes all cases in which a biopsy read by the central pathologist demonstrates acute rejection, regardless of the reason that the biopsy was performed.
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Through Months 6 and 12 posttransplant (From Day 1 to Months 6 and 12)
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Percentage of Participants With Biopsy-proven Acute Rejection (BPAR) or Who Received Treatment for Acute Rejection
Periodo de tiempo: By Months 3, 6, and 12 posttransplant (Day 1 to Months 3, 6, and 12)
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BPAR includes all cases in which a biopsy read by the central pathologist demonstrates acute rejection, regardless of the reason that the biopsy was performed.
A participant was reported as having had an episode of treated acute rejection if he or she received antirejection therapy during an episode of rejection (clinically-suspected or biopsy-proven rejection).
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By Months 3, 6, and 12 posttransplant (Day 1 to Months 3, 6, and 12)
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Percentage of Participants With Acute Rejection or Presumed Acute Rejection (PAR)
Periodo de tiempo: By Months 6 and 12 posttransplant (Day 1 to Months 6 and 12)
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Throughout this study, acute rejection=clinically-suspected and biopsy-proven acute rejection (BPAR).
Clinically-suspected rejection is defined as an increase in serum creatinine ≥0.5 mg/dL compared with the baseline value in the absence of other factors known to adversely affect renal function.
BPAR includes all cases in which a biopsy was read by the central pathologist as demonstrating acute rejection regardless of the reason why the biopsy was performed.
PAR is defined as an elevation in SCr ≥0.5 mg/dL compared with the baseline value in the absence of other factors known to adversely affect renal function that led the investigator to suspect that the participant had experienced acute rejection, and in whom either the biopsy did not confirm acute rejection and the participant received treatment for acute rejection or the participant received treatment for acute rejection without a biopsy to confirm the diagnosis.
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By Months 6 and 12 posttransplant (Day 1 to Months 6 and 12)
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Percentage of Participants Who Had Chronic Allograft Nephropathy
Periodo de tiempo: By Months 6 and 12 posttransplant (Day 1 to Months 6 and 12)
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Based on postbaseline biopsies
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By Months 6 and 12 posttransplant (Day 1 to Months 6 and 12)
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Mean Iohexol Clearance
Periodo de tiempo: By Months 1, 6, and 12 posttransplant (Day 1 to Months 1, 6, and 12)
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Iohexol, a true glomerular filtration marker, is used to measure glomerular filtration rate.
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By Months 1, 6, and 12 posttransplant (Day 1 to Months 1, 6, and 12)
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Percentage of Participants Who Used Antihypertensive Medication
Periodo de tiempo: By Months 6 and 12 posttransplant (Day 1 to Months 6 and 12)
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Hypertension is defined as diastolic blood pressure ≥90 mm Hg and/or systolic blood pressure ≥140 mm Hg
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By Months 6 and 12 posttransplant (Day 1 to Months 6 and 12)
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Number of Participants With Hypertension
Periodo de tiempo: By Months 6 and 12 posttransplant (Day 1 to Months 6 and 12)
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Hypertension is defined as diastolic blood pressure ≥90 mm Hg and/or systolic blood pressure ≥140 mm Hg or, the use of any antihypertensive medication.
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By Months 6 and 12 posttransplant (Day 1 to Months 6 and 12)
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Mean LDL Cholesterol, HDL Cholesterol, Total Cholesterol, Triglyceride, and Non-HDL Levels
Periodo de tiempo: By Months 1, 6, and 12 posttransplant (Day 1 to Months 1, 6, and 12)
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LDL=low-density lipoprotein; HDL=high-density lipoprotein.
Total cholesterol=LDL + HDL + very low-density (VLDL) cholesterol.
VLDL=triglycerides divided by 5. Non-HDL cholesterol=Total cholesterol minus HDL cholesterol.
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By Months 1, 6, and 12 posttransplant (Day 1 to Months 1, 6, and 12)
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Number of Participants With Posttransplant Diabetes Mellitus
Periodo de tiempo: By Months 1, 3, 6, 9, and 12 posttransplant (Day 1 to Months 1, 3, 6, 9, and 12 )
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Posttransplant diabetes mellitus is defined as the need for treatment of hyperglycemia with either an oral agent or insulin for a total of >4 weeks or hemoglobin A1c (HbA1c) >7% in a participant not known to be diabetic prior to transplantation
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By Months 1, 3, 6, 9, and 12 posttransplant (Day 1 to Months 1, 3, 6, 9, and 12 )
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Otras medidas de resultado
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Treatment-related SAEs, Discontinuations Due to SAEs, Adverse Events (AEs), Treatment-related AEs, and Discontinuations Due to AEs
Periodo de tiempo: Day 1 (posttransplant) continuously to 56 days following last dose of study medication
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AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment.
SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization.
Treatment-related=having certain, probable, possible, or missing relationship to study drug.
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Day 1 (posttransplant) continuously to 56 days following last dose of study medication
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Number of Participants Meeting Marked Abnormality Criteria for Select Hemolytic, Blood Chemistry, and Urinalysis Laboratory Test Results
Periodo de tiempo: Days 8 and Months 1, 3, 6, 9, and 12 posttransplant (from Day 1)
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Normal laboratory values: Hemoglobin (g/dL): Males (18-64 years) 13.8-17, (65 years and older) 11.8-16.8;
Females (18-64 years) 12.0-15.6,
F (65 years and older) 11.1-15.5.
Platelets (per mm^3) 130,000-400,000.
Leukocytes (18 years and older) 3.8-10.8
1000/uL.
ALT (u/L)(13 years and older) 0-48.
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Days 8 and Months 1, 3, 6, 9, and 12 posttransplant (from Day 1)
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Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Patrocinador
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 marzo de 2001
Finalización primaria (Actual)
1 de enero de 2004
Finalización del estudio (Actual)
1 de julio de 2012
Fechas de registro del estudio
Enviado por primera vez
3 de mayo de 2002
Primero enviado que cumplió con los criterios de control de calidad
3 de mayo de 2002
Publicado por primera vez (Estimar)
6 de mayo de 2002
Actualizaciones de registros de estudio
Última actualización publicada (Estimar)
13 de enero de 2014
Última actualización enviada que cumplió con los criterios de control de calidad
27 de noviembre de 2013
Última verificación
1 de noviembre de 2013
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
- Efectos fisiológicos de las drogas
- Mecanismos moleculares de acción farmacológica
- Agentes antiinfecciosos
- Inhibidores de enzimas
- Agentes antirreumáticos
- Agentes antineoplásicos
- Agentes inmunosupresores
- Factores inmunológicos
- Agentes dermatológicos
- Agentes antibacterianos
- Antibióticos, Antineoplásicos
- Agentes antifúngicos
- Inhibidores de puntos de control inmunitarios
- Agentes antituberculosos
- Antibióticos, Antituberculosos
- Inhibidores de calcineurina
- Ácido micofenólico
- Abatacept
- Ciclosporina
- Ciclosporinas
Otros números de identificación del estudio
- IM103-100
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. .
Ensayos clínicos sobre Belatacept
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Lorenzo GallonBristol-Myers SquibbTerminadoVEB | Trasplante; Insuficiencia, RiñónEstados Unidos
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University of MarylandBristol-Myers SquibbTerminadoEnfermedad renal en etapa terminalEstados Unidos
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East Carolina UniversityTerminado
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