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Efficacy and Safety Study of Abatacept to Treat Lupus Nephritis

3 de marzo de 2015 actualizado por: Bristol-Myers Squibb

A Phase II/III Multi-Center, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Abatacept Versus Placebo on a Background of Mycophenolate Mofetil and Glucocorticosteroids in Subjects With Active Proliferative Glomerulonephritis Due to Systemic Lupus Erythematosus (SLE)

The purpose of this clinical research study is to learn if addition of abatacept is safe and improves the effectiveness of treatment of patients with active lupus nephritis who are also taking mycophenolate mofetil (MMF) and corticosteroids.

Descripción general del estudio

Estado

Terminado

Condiciones

Intervención / Tratamiento

Descripción detallada

Double Blind Period: Treatment, Parallel Assignment, Double Blind (Subject, Investigator), Randomized, Active Control, Safety/Efficacy Study

Open Label Period: Prevention, Single Group Assignment, Open Label, Uncontrolled, Safety/Efficacy Study

Tipo de estudio

Intervencionista

Inscripción (Actual)

423

Fase

  • Fase 2
  • 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

  • Argentina
      • Cordoba, Argentina, 5016
        • Local Institution
      • Tucuman, Argentina, 4000
        • Local Institution
    • Buenos Aires
      • Capital Federal, Buenos Aires, Argentina, 1015
        • Local Institution
      • Ciudad Autonoma De Buenos Aire, Buenos Aires, Argentina, 1055
        • Local Institution
  • Australia
    • New South Wales
      • Liverpool, New South Wales, Australia, 2170
        • Local Institution
    • Victoria
      • Clayton, Victoria, Australia, 3168
        • Local Institution
      • Heidelberg, Victoria, Australia, 3084
        • Local Institution
      • Parkville, Victoria, Australia, 3050
        • Local Institution
  • Brasil
      • Rio De Janeiro, Brasil, 20551
        • Local Institution
      • Sao Paulo, Brasil, 04026
        • Local Institution
    • Goias
      • Goiania, Goias, Brasil, 74110
        • Local Institution
    • Parana
      • Curitiba, Parana, Brasil, 80060
        • Local Institution
    • Rio Grande Do Sul
      • Porto Alegre, Rio Grande Do Sul, Brasil, 91610
        • Local Institution
  • Bélgica
      • Bruxelles, Bélgica, 1200
        • Local Institution
      • Leuven, Bélgica, 3000
        • Local Institution
  • Canadá
      • Quebec, Canadá, G1R 2J6
        • Local Institution
    • Alberta
      • Edmonton, Alberta, Canadá, T6G 2S2
        • Local Institution
    • Manitoba
      • Winnipeg, Manitoba, Canadá, R3A 1M4
        • Local Institution
    • Ontario
      • Toronto, Ontario, Canadá, M5T 2S8
        • Local Institution
  • Corea, república de
      • Seoul, Corea, república de, 110-744
        • Local Institution
      • Seoul, Corea, república de, 137-040
        • Local Institution
    • Sungdong-Gu
      • Seoul, Sungdong-Gu, Corea, república de, 133-792
        • Local Institution
  • Estados Unidos
    • Alabama
      • Birmingham, Alabama, Estados Unidos, 35294
        • University of Alabama at Birmingham
    • Arizona
      • Tucson, Arizona, Estados Unidos, 85724
        • Arizona Arthritis Center
    • California
      • Los Angeles, California, Estados Unidos, 90048
        • Wallace Rheumatic Study Center
    • Kansas
      • Kansas City, Kansas, Estados Unidos, 66160
        • University of Kansas Medical Center
    • Massachusetts
      • Boston, Massachusetts, Estados Unidos, 02118
        • Boston University School of Medicine
    • Minnesota
      • Minneapolis, Minnesota, Estados Unidos, 55415
        • Hennepin County Medical Center
    • New York
      • Brooklyn, New York, Estados Unidos, 11203
        • SUNY Downstate Medical Center
      • Lake Success, New York, Estados Unidos, 11042
        • Northshore Lij Health System
      • Manhasset, New York, Estados Unidos, 11030
        • The Feinstein Institute for Medical Research
      • Syracuse, New York, Estados Unidos, 13210
        • SUNY Upstate Medical University
    • North Carolina
      • Chapel Hill, North Carolina, Estados Unidos, 27599
        • University of North Carolina at Chapel Hill
    • Oklahoma
      • Oklahoma City, Oklahoma, Estados Unidos, 73104
        • Ok Medical Research Foundation
    • Tennessee
      • Knoxville, Tennessee, Estados Unidos, 37909
        • Rheumatology Consultants Pllc
    • Washington
      • Seattle, Washington, Estados Unidos, 98101
        • Virginia Mason Medical Center
  • Federación Rusa
      • Ekaterinburg, Federación Rusa, 620102
        • Local Institution
      • Moscow, Federación Rusa, 115522
        • Local Institution
      • Yaroslaval, Federación Rusa, 150062
        • Local Institution
  • Francia
      • Creteil Cedex, Francia, 94010
        • Local Institution
      • Paris Cedex 13, Francia, 75651
        • Local Institution
      • Strasbourg Cedex, Francia, 67098
        • Local Institution
      • Toulouse Cedex 4, Francia, 31403
        • Local Institution
  • Hong Kong
      • Hong Kong, Hong Kong
        • Local Institution
  • India
      • Hyderabad, India, 500082
        • Local Institution
      • Visakhapatnam, India, 530002
        • Local Institution
    • Ahmedabad
      • Gujarat, Ahmedabad, India, 380016
        • Local Institution
    • Andhra Pradesh
      • Secunderabad, Andhra Pradesh, India, 500003
        • Local Institution
    • Gujarat
      • Ahmedabad, Gujarat, India, 380 007
        • Local Institution
      • Nadiad, Gujarat, India, 387001
        • Local Institution
    • Karnataka
      • Bangalore, Karnataka, India, 560 034
        • Local Institution
      • Bangalore, Karnataka, India, 560 017
        • Local Institution
    • Kerala
      • Kochi, Kerala, India, 682026
        • Local Institution
    • Maharajhsra
      • Mumbai, Maharajhsra, India, 400064
        • Local Institution
  • México
      • Aguascalientes, México, 20000
        • Local Institution
      • San Luis Potosi, México, 78240
        • Local Institution
    • Distrito Federal
      • Mexico City, Distrito Federal, México, 06726
        • Local Institution
    • Estado De Mexico
      • Metepec, Estado De Mexico, México, 52140
        • Local Institution
    • Jalisco
      • Guadalajara, Jalisco, México, 44100
        • Local Institution
      • Guadalajara, Jalisco, México, 44690
        • Local Institution
    • Nuevo Leon
      • Monterrey, Nuevo Leon, México, 64020
        • Local Institution
    • Yucatan
      • Merida, Yucatan, México, 97000
        • Local Institution
  • Pavo
      • Gaziantep, Pavo, 27310
        • Local Institution
  • Polonia
      • Bydgoszcz, Polonia, 85-094
        • Local Institution
      • Gdansk, Polonia, 80-952
        • Local Institution
      • Wroclaw, Polonia, 50-417
        • Local Institution
  • Porcelana
    • Beijing
      • Beijing, Beijing, Porcelana, 100034
        • Local Institution
      • Beijing, Beijing, Porcelana, 100730
        • Local Institution
      • Beijing, Beijing, Porcelana, 100044
        • Local Institution
      • Beijing, Beijing, Porcelana, 100853
        • Local Institution
    • Guangdong
      • Guangzhou, Guangdong, Porcelana, 510080
        • Local Institution
    • Shanghai
      • Shanghai, Shanghai, Porcelana, 200025
        • Local Institution
      • Shanghai, Shanghai, Porcelana, 200001
        • Local Institution
    • Shanxi
      • Xi'an, Shanxi, Porcelana, 710032
        • Local Institution
  • Reino Unido
    • Cambridgeshire
      • Cambridge, Cambridgeshire, Reino Unido, CB2 2QQ
        • Local Institution
    • Greater London
      • London, Greater London, Reino Unido, SE1 7EX
        • Local Institution
  • Sudáfrica
    • Gauteng
      • Johannesburg, Gauteng, Sudáfrica, 2013
        • Local Institution
    • Western Cape
      • Observatory, Western Cape, Sudáfrica, 7925
        • Local Institution
      • Panorama, Western Cape, Sudáfrica, 7500
        • Local Institution
  • Taiwán
      • Kaohsiung, Taiwán, 833
        • Local Institution
      • Taichung, Taiwán, 402
        • Local Institution
      • Taichung, Taiwán, 407
        • Local Institution
      • Taipei, Taiwán, 11217
        • Local Institution
      • Taoyuan, Taiwán, 333
        • Local Institution

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:

  • Systemic Lupus Erythematosus (SLE) as defined by meeting at least 4 of the 11 classification criteria of the American College of Rheumatology for the classification of Systemic Lupus Erythematosus, either sequentially or coincident. The 4 criteria need not be present at study entry
  • Renal biopsy within 12 months prior to screening visit indicating active proliferative lupus glomerulonephritis (met ISN/RPS Class III or IV classification criteria [2003], excluding Class III [C], IV-S [C] and IV-G [C], or the World Health Organization Class III or IV classification criteria [1982], excluding Class IIIc, IVd). If the renal biopsy was performed >3 months but ≤12 months prior to screening visit, at least 1 of the following 3 serologies (performed locally) must have been abnormal prior to screening visit: complement (C3 or C4) level below normal range OR anti-dsDNA >upper limit of normal range.
  • A stable serum creatinine ≤3 mg/dL

Exclusion Criteria:

  • Subjects with a rise in serum creatinine of ≥1 mg/dL within 1 month prior to the screening visit
  • Subjects with drug-induced SLE, as opposed to idiopathic SLE
  • Subjects with severe, unstable and/or progressive Central nervous system (CNS) lupus
  • Subjects with autoimmune disease other than SLE as their main diagnosis (e.g.; Rheumatoid arthritis (RA), Multiple Sclerosis [MS])
  • Subjects who have received treatment with cyclophosphamide within 3 months of randomization (Day 1).
  • Subjects who have received treatment with rituximab < 6 months prior to the screening 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: Tratamiento
  • Asignación: Aleatorizado
  • Modelo Intervencionista: Asignación paralela
  • Enmascaramiento: Doble

Armas e Intervenciones

Grupo de participantes/brazo
Intervención / Tratamiento
Experimental: Abatacept 30 mg/kg+Corticosteroids+MMF
Short-term Period
Droga: Corticosteroids (prednisone or prednisolone)
tablets, oral, 0.5-0.8 mg/kg, daily
Droga: Abatacept
intravenous solution, injectable, 30 mg/kg, every 28 days
Otros nombres:
  • Orencia
  • BMS-188667
Droga: Abatacept
intravenous solution, injectable, 10 mg/kg, every 28 days
Otros nombres:
  • Orencia
  • BMS-188667
Droga: Mycophenolate mofetil (MMF)
tablets, oral, 1.5 to 2 g, daily
Experimental: Abatacept 10 mg/kg+Corticosteroids+MMF
Short-term Period
Droga: Corticosteroids (prednisone or prednisolone)
tablets, oral, 0.5-0.8 mg/kg, daily
Droga: Abatacept
intravenous solution, injectable, 30 mg/kg, every 28 days
Otros nombres:
  • Orencia
  • BMS-188667
Droga: Abatacept
intravenous solution, injectable, 10 mg/kg, every 28 days
Otros nombres:
  • Orencia
  • BMS-188667
Droga: Mycophenolate mofetil (MMF)
tablets, oral, 1.5 to 2 g, daily
Experimental: Placebo+Corticosteroids+MMF
Short-term Period
Droga: Corticosteroids (prednisone or prednisolone)
tablets, oral, 0.5-0.8 mg/kg, daily
Droga: Mycophenolate mofetil (MMF)
tablets, oral, 1.5 to 2 g, daily
Experimental: Abatacept 10mg/kg
Long-term Extension Period
Droga: Abatacept
intravenous solution, injectable, 30 mg/kg, every 28 days
Otros nombres:
  • Orencia
  • BMS-188667
Droga: Abatacept
intravenous solution, injectable, 10 mg/kg, every 28 days
Otros nombres:
  • Orencia
  • BMS-188667

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Time to First Confirmed Complete Renal Response (CRR) During the Short-term (Double-blind) Period
Periodo de tiempo: Day 1 (randomization) to 12 months.
Confirmed at 2 consecutive visits. CRR defined as meeting all of 5 criteria. Renal function (RF): (Glomerular filtration rate [GFR] calculated using Modification of Diet in Renal Diseases equation equation) Calculated function abnormal at screening visit - return of renal function to greater than or equal to 90% of function at approximately 6 months prior to onset of the current episode of lupus nephritis. Calculated function normal at screening visit - estimated renal function 90% or greater of level at screening visit. Proteinuria: urinary protein/creatinine ratio <30 mg/mmol. Hematuria: red blood cell (RBC) count within normal limits of Central Laboratory. Pyuria: White blood cell count (WBC) within normal limits of Central Laboratory. Cylindruria: No RBC or WBC casts reported.
Day 1 (randomization) to 12 months.

Medidas de resultado secundarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Number of Participants With Confirmed Complete Renal Response (CRR) During Short-term Period
Periodo de tiempo: Day 1 to 12 months
Confirmed at 2 consecutive visits. CRR defined as meeting all of 5 criteria. Renal function (RF): (Glomerular filtration rate [GFR] calculated using Modification of Diet in Renal Diseases equation equation) Calculated function abnormal at screening visit - return of renal function to greater than or equal to 90% of function at approximately 6 months prior to onset of the current episode of lupus nephritis. Calculated function normal at screening visit - estimated renal function 90% or greater of level at screening visit. Proteinuria: urinary protein/creatinine ratio <30 mg/mmol. Hematuria: red blood cell (RBC) count within normal limits of Central Laboratory. Pyuria: White blood cell count (WBC) within normal limits of Central Laboratory. Cylindruria: No RBC or WBC casts reported.
Day 1 to 12 months
Participants Achieving a Confirmed Complete Renal Response (CRR) at Month 12 During Short-term Period
Periodo de tiempo: At Month 12 from Day 1
Confirmed at 2 consecutive visits. CRR defined as meeting all of 5 criteria. Renal function (RF): (Glomerular filtration rate [GFR] calculated using Modification of Diet in Renal Diseases equation equation) Calculated function abnormal at screening visit - return of renal function to greater than or equal to 90% of function at approximately 6 months prior to onset of the current episode of lupus nephritis. Calculated function normal at screening visit - estimated renal function 90% or greater of level at screening visit. Proteinuria: urinary protein/creatinine ratio <30 mg/mmol. Hematuria: red blood cell (RBC) count within normal limits of Central Laboratory. Pyuria: White blood cell count (WBC) within normal limits of Central Laboratory. Cylindruria: No RBC or WBC casts reported.
At Month 12 from Day 1
Time to Achieve First Confirmed Renal Improvement (RI) During Short-term Period (as Determined by Kaplan-Meier Methodology)
Periodo de tiempo: Day 1 (randomization) to 12 months.
RI is defined as meeting all of the following criteria. Renal function: If MDRD is abnormal at screening, within 10% of the MDRD at screening; if MDRD is 60-89 at screening, greater than or equal to 50% improvement based on the screening value or 90% or greater of MDRD at screening; if MDRD is 15-59 at screening, if MDRD is normal at screening-within 10% of the MDRD at screening. Proteinuria: improvement greater than or equal to 50% from screening. Hematuria: red blood cell (RBC)count within normal limit of central laboratory. Pyuria: white blood cell (WBC) count within normal limit of central laboratory. Cylindruria: No RBC or WBC casts.
Day 1 (randomization) to 12 months.
Participants Achieving Renal Improvement (RI) or CRR at Month 12 During Short-term Period
Periodo de tiempo: At Month 12 from Day 1
CRR defined as meeting all of 5 criteria. RF: (Glomerular filtration rate [GFR] calculated using MDRD equation) Calculated function abnormal at screening visit - return of renal function to greater than or equal to 90% of function at approximately 6 months prior to onset of the current episode of lupus nephritis. Calculated function normal at screening visit - estimated renal function 90% or greater of level at screening visit. Proteinuria: urinary protein/creatinine ratio <30 mg/mmol. Hematuria: red blood cell (RBC) count within normal limits of Central Laboratory. Pyuria: White blood cell count (WBC) within normal limits of Central Laboratory. Cylindruria: No RBC or WBC casts reported.
At Month 12 from Day 1
Number of Months CRR Was Maintained During Short-term Period
Periodo de tiempo: Day 1 (randomization) to 12 Months
Durability of CRR, defined as the number of months (number of consecutive planned visits beyond Day 15) a participant met the definition of CRR during the double-blind treatment period. Refer to outcome 1 for description of CRR.
Day 1 (randomization) to 12 Months
Baseline Renal Function Over Time During Short-term Period
Periodo de tiempo: Baseline (Day 1), Day 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, 337, 365
Baseline (BL) renal function, as estimated by calculation of the MDRD (Modification of Diet in Renal Disease) equation, over time. Renal MDRD is an equation (calculation) used to estimate Glomerular Filtration Rate (GFR) in participants with impaired renal function based on serum creatinine, age, race, and gender. GFR (mL/min/1.73 m^2) = 175 * (Scr)^-1.154 * (Age)^-0.203 * (0.742 if female) * (1.212 if African American) (conventional units). mL, milliliters; min, minute; m^2, meters squared; Scr, serum creatinine. A negative value indicates worsening.
Baseline (Day 1), Day 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, 337, 365
Change in Renal Function From Baseline Over Time During Short-term Period
Periodo de tiempo: Baseline (Day 1), Day 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, 337, 365
Mean change from baseline in renal function, as estimated by calculation of the MDRD equation, over time. Renal MDRD is an equation (calculation) used to estimate Glomerular Filtration Rate (GFR) in participants with impaired renal function based on serum creatinine, age, race, and gender. GFR (mL/min/1.73 m^2) = 175 * (Scr)^-1.154 * (Age)^-0.203 * (0.742 if female) * (1.212 if African American) (conventional units). mL, milliliters; min, minute; m^2, meters squared; Scr, serum creatinine. A positive value indicates improvement. Change from baseline=Post-baseline-baseline value.
Baseline (Day 1), Day 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, 337, 365
Baseline and Post Baseline Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology (ACR) Damage Index During Short-term Period
Periodo de tiempo: Baseline (Day 1), Post baseline (Month 12 or 28 days after last dose)
SLICC/ACR score or damage index is a measure of cumulative damage due to Systemic Lupus Erythematosus (SLE). Damage is defined as nonreversible change (not related to active inflammation) occurring since onset of lupus, ascertained by clinical assessment and present for at least 6 months. A score of 0=no damage, early damage is defined as ≥1. The total maximum score is 48, and increasing score indicates increasing disease severity.
Baseline (Day 1), Post baseline (Month 12 or 28 days after last dose)
Number of Participants Achieving Renal Response (RR) at Month 12 During Short-term Period
Periodo de tiempo: Month 12
RR is defined as meeting BOTH of the following criteria:RENAL FUNCTION: Less than or equal to 25% increase from baseline;PROTEINURIA: Greater than or equal to 50% improvement in the urine protein/creatinine ratio with one of the following - urine protein/creatinine ratio (UPCR) <113 mg/mmol,, if the baseline ratio was <=339 mg/mmol OR UPCR <339 mg/mmol,if the baseline ratio > 339 mg/mmol. A participant was considered as achieving RR if response criteria at both months 11 and 12 (Days 337 and 365, respectively) were met. For 95% CI within each group, normal approximation is used if n>=5.
Month 12
Change in SLICC/ACR Damage Index From Baseline During Short-term Period
Periodo de tiempo: Baseline (Day 1), Postbaseline (Month 12 or 28 days after last dose)
SLICC/ACR score or damage index is a measure of cumulative damage due to Systemic Lupus Erythematosus (SLE). Damage is defined as non-reversible change (not related to active inflammation) occurring since onset of lupus, ascertained by clinical assessment and present for at least 6 months. A score of 0=no damage, early damage is defined as ≥1. The total maximum score is 48, and increasing score indicates increasing disease severity. Change from baseline=Postbaseline - baseline value.
Baseline (Day 1), Postbaseline (Month 12 or 28 days after last dose)
Baseline Physical Component Summary of the Short Form (SF)-36 During Short-term Period
Periodo de tiempo: Baseline (Day 1), Days 85, 169, 253, and 365
The SF-36 is a validated instrument measuring health-related quality of life across multiple disease states. It has 36 questions with 8 subscale scores and 2 summary scores (1) physical component summary=physical functioning, role-physical, bodily pain, and general health; (2) mental component summary=vitality, social functioning, role-emotional, and mental health. There is no total overall score; scoring is done for both subscores and summary scores. For subscores and summary scores, 0 =worst score (or quality of life) and 100=best score. Change from Baseline= post-Baseline - Baseline value.
Baseline (Day 1), Days 85, 169, 253, and 365
Change From Baseline in Physical Component Summary of the SF-36 During Short-term Period
Periodo de tiempo: Baseline (Day 1), Days 85, 169, 253, and 365
The SF-36 is a validated instrument measuring health-related quality of life across multiple disease states. It has 36 questions with 8 subscale scores and 2 summary scores (1) physical component summary=physical functioning, role-physical, bodily pain, and general health; (2) mental component summary=vitality, social functioning, role-emotional, and mental health. There is no total overall score; scoring is done for both subscores and summary scores. For subscores and summary scores, 0 =worst score (or quality of life) and 100=best score. Change from Baseline= post-Baseline - Baseline value.
Baseline (Day 1), Days 85, 169, 253, and 365
Baseline Mental Component Summary of the Short SF-36 During Short-term Period
Periodo de tiempo: Baseline (Day 1), Days 85, 169, 253, and 365
The SF-36 is a validated instrument measuring health-related quality of life across multiple disease states. It has 36 questions with 8 subscale scores and 2 summary scores (1) physical component summary=physical functioning, role-physical, bodily pain, and general health; (2) mental component summary=vitality, social functioning, role-emotional, and mental health. There is no total overall score; scoring is done for both subscores and summary scores. For subscores and summary scores, 0 =worst score (or quality of life) and 100=best score. Change from Baseline= post-Baseline - Baseline value.
Baseline (Day 1), Days 85, 169, 253, and 365
Change From Baseline in Mental Component Summary of the SF-36 During Short-term Period
Periodo de tiempo: Baseline (Day 1), Days 85, 169, 253, and 365
The SF-36 is a validated instrument measuring health-related quality of life across multiple disease states. It has 36 questions with 8 subscale scores and 2 summary scores (1) physical component summary=physical functioning, role-physical, bodily pain, and general health; (2) mental component summary=vitality, social functioning, role-emotional, and mental health. There is no total overall score; scoring is done for both subscores and summary scores. For subscores and summary scores, 0 =worst score (or quality of life) and 100=best score. Change from Baseline= post-Baseline - Baseline value.
Baseline (Day 1), Days 85, 169, 253, and 365
Baseline Fatigue as Measured by the Fatigue Visual Analog Scale During Short-term Period
Periodo de tiempo: Baseline (Day 1), Days 85, 169, 253, and 365
A visual analogue scale (VAS) is a psychometric response scale for measurement of subjective characteristics or attitudes that cannot be directly measured. The VAS for Fatigue (VAS-F) consists of a 100 mm line, with 0 (No Fatigue) on 1 end and 100 (Extreme Fatigue) on the other end, which a participant marks to indicate how much fatigue he or she feels. The marked point in mm is converted into a numeric value from 0 to 100, where 0=no fatigue and 100=maximum fatigue. Increasing numbers=increasing fatigue.
Baseline (Day 1), Days 85, 169, 253, and 365
Change in Fatigue From Baseline as Measured by the Fatigue Visual Analog Scale During Short-term Period
Periodo de tiempo: Baseline (Day 1), Days 85, 169, 253, and 365

A visual analogue scale is a psychometric response scale for measurement of subjective characteristics or attitudes that cannot be directly measured.

The VAS for Fatigue (VAS-F) consists of a 100 mm line, with 0 (No Fatigue) on 1 end and 100 (Extreme Fatigue) on the other end, which a participant marks to indicate how much fatigue he or she feels. The marked point in mm is converted into a numeric value from 0 to 100, where 0=no fatigue and 100=maximum fatigue. Increasing numbers=increasing fatigue.
Baseline (Day 1), Days 85, 169, 253, and 365
Baseline Fatigue as Measured by Fatigue Severity Scale-Krupp During Short-term Period
Periodo de tiempo: Baseline (Day 1), Days 85, 169, 253, and 365
The reduction of fatigue assessed by Fatigue Severity Scale (FSS). The FSS questionnaire is comprised of 9 statements inquiring about the examinee's sleep habits over the preceding week. Participants are asked to rate their level of agreement (toward seven) or disagreement (toward zero) with the nine statements. A score of 36 and above (out of a maximum of 63) indicates the presence of significant fatigue.
Baseline (Day 1), Days 85, 169, 253, and 365
Change in Fatigue From Baseline as Measured by Fatigue Severity Scale-Krupp During Short-term Period
Periodo de tiempo: Baseline (Day 1), Days 85, 169, 253, and 365
The reduction of fatigue assessed by Fatigue Severity Scale (FSS). The FSS questionnaire is comprised of 9 statements inquiring about the examinee's sleep habits over the preceding week. Participants are asked to rate their level of agreement (toward seven) or disagreement (toward zero) with the nine statements. A score of 36 and above (out of a maximum of 63) indicates the presence of significant fatigue.
Baseline (Day 1), Days 85, 169, 253, and 365
Participants With Adverse Events (AEs), Serious AEs (SAEs), Deaths, and Discontinuations Due to AEs Reported During the Short-term Period
Periodo de tiempo: From Baseline (Day 1) up to 56 days post last dose in the double-blind period or the first dose in the open-label long-term extension, whichever occurred first.
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. Related=possibly, probably, or certainly related to and of unknown relationship to study drug.
From Baseline (Day 1) up to 56 days post last dose in the double-blind period or the first dose in the open-label long-term extension, whichever occurred first.
Participants With AEs of Special Interest During the Short-term Period
Periodo de tiempo: From Baseline (Day 1) up to 56 days post last dose in the double-blind period or the first dose in the open-label long-term extension, whichever occurred first.
AEs of special interest were prospectively identified to be those that may be associated with the use of immunomodulatory agents. They are a subset of all AEs and may be either serious or non-serious.
From Baseline (Day 1) up to 56 days post last dose in the double-blind period or the first dose in the open-label long-term extension, whichever occurred first.
Participants With Marked Hematology Abnormalities During the Short-term Period
Periodo de tiempo: From Baseline (Day 1) up to 56 days post last dose in the double-blind period or the first dose in the open-label long-term extension, whichever occurred first.
LLN=lower limit of normal; ULN=upper limit of normal; PTV=pretreatment value. Normal ranges are provided by the Central Laboratory and may vary according to sex and age. Low(↓)Hemoglobin:>3g/dL decrease from PTV; ↓Hematocrit:<0.75xPTV;↓Erythrocyte count:<0.75xPTV; high(↑)Platelet count:>1.5xULN;↓Platelet count:<0.67xLLN;↓Leukocyte count:<0.75X LLN;↑Leukocyte count:>1.25xULN;↓Absolute(AB)Neutrophils+Bands:<1.00x10^3c/uL;↑AB Lymphocyte count:>7.50x10^3 c/uL; ↓AB lymphocyte count:<0.750x10^3 c/uL;↑AB monocyte count:>2000/mm^3;↑AB basophil count:>400/mm^3;↑AB eosinophil count:>0.750x10^3 c/uL.
From Baseline (Day 1) up to 56 days post last dose in the double-blind period or the first dose in the open-label long-term extension, whichever occurred first.
Participants With Marked Laboratory Abnormalities During the Short-term Period
Periodo de tiempo: From Baseline (Day 1) up to 56 days post last dose in the double-blind period or the first dose in the open-label long-term extension, whichever occurred first.
LLN=lower limit of normal; ULN=upper limit of normal; PTV=pretreatment value. Normal ranges are provided by the Central Laboratory and may vary according to sex and age. ↑Serum Sodium:>1.05x ULN;↓Serum Potassium:<0.9x LLN;↑Serum Potassium:>1.1x ULN;↓Total Calcium:<0.8X LLN;↑Total Calcium:>1.2x ULN; ↓Serum Glucose(SG):<65 mg/dL;↑SG:>220 mg/dL;↓Fasting SG:<0.8x LLN;↑Fasting SG:>1.5x ULN;↓Total Protein:<0.9x LLN;↓Albumin:<0.9x LLN;↑Total Cholesterol:>2x PTV;↑Triglycerides:>=2.5x ULN;↑Fasting Triglycerides:>=2x ULN
From Baseline (Day 1) up to 56 days post last dose in the double-blind period or the first dose in the open-label long-term extension, whichever occurred first.
Participants With Marked Liver and Kidney Function Abnormalities During the Short-term Period
Periodo de tiempo: From Baseline (Day 1) up to 56 days post last dose in the double-blind period or the first dose in the open-label long-term extension, whichever occurred first.

ULN=upper limit of normal; PTV=pretreatment value. Normal ranges are provided by the Central Laboratory and may vary according to sex and age.

Alkaline Phosphatase:>2x ULN; ↑Aspartate Aminotransferase: >3x ULN; ↑Alanine Aminotransferase : >3x ULN; G-Glutamyl Transferase : >2x ULN; ↑Total Bilirubin : >2x ULN or if PTV > ULN then > 4x PTV; ↑Blood Urea Nitrogen >2x PTV; ↑Creatinine >1.5x PTV.
From Baseline (Day 1) up to 56 days post last dose in the double-blind period or the first dose in the open-label long-term extension, whichever occurred first.
Participants With Marked Abnormalities Urinalysis During the Short-term Period
Periodo de tiempo: From Baseline (Day 1) up to 56 days post last dose in the double-blind period or the first dose in the open-label long-term extension, whichever occurred first.
PTV=pretreatment value. Criteria for marked abnormality: Protein, glucose, blood, leukocyte esterase , if missing PTV then use >=2+ (or, if value >=4, or if PTV=0 or 0.5, >=2 or if PTV=1, >=3, or if PTV=2 or 3, >=4).
From Baseline (Day 1) up to 56 days post last dose in the double-blind period or the first dose in the open-label long-term extension, whichever occurred first.
Vital Signs Summary During the Short-term Period: Systolic Blood Pressure (SBP)
Periodo de tiempo: 0 - 12 Months
0 - 12 Months
Vital Signs Summary During the Short-term Period: Diastolic Blood Pressure (DBP)
Periodo de tiempo: 0 - 12 Months
0 - 12 Months
Vital Signs Summary During the Short-term Period: Heart Rate
Periodo de tiempo: 0 - 12 Months
0 - 12 Months
Vital Signs Summary During the Short-term Period: Temperature
Periodo de tiempo: 0 - 12 Months
0 - 12 Months
Number of Participants With Positive Abatacept-induced Responses (ECL Method) Over Time During the Short-term Period
Periodo de tiempo: Day 169, Day 365
A validated, sensitive electrochemiluminescence (ECL) immunoassay based on Meso-Scale Discovery instrumentation was used to evaluate immunogenicity. The ECL assay differentiated between two antibody specificities: (1) the 'Ig and/or Junction (Jn) Region' and (2) 'CLTA4 and possibly Ig'. A sample was considered positive if it had a titer of 10 or greater and if immunodepletion was observed with abatacept with or without CTLA4-T.
Day 169, Day 365
Baseline Quantitative Immunoglobulins During the Short-term Period
Periodo de tiempo: Baseline (Day 1)
A quantitative immunoglobulins (Igs) test is used to detect abnormal levels of the three major classes of Igs (IgG, IgA, and IgM). Abnormal test results typically indicate that there is something affecting the immune system which requires further testing.
Baseline (Day 1)
Change in Quantitative Immunoglobulin From Baseline During Short-term Period
Periodo de tiempo: Day 365

A quantitative immunoglobulin (Ig) test is used to detect abnormal levels of the 3 major classes of Ig (IgG, IgA, and IgM). Abnormal test results typically indicate that something is affecting the immune system and further testing is required.

Please refer to Outcome 31 for the respective baseline values
Day 365
Number of Participants Achieving Complete Response by ACCESS Definition
Periodo de tiempo: End of short-term period (Day 365) to termination of the long-term extension period
The Abatacept and Cyclophosphamide Combination Efficacy and Safety Study (ACCESS) defines complete response as a response meeting all of the following criteria: serum creatinine ≤upper limit of normal as defined by the central laboratory or ≤125% of the higher value at either screening or baseline; urine protein/creatinine ratio <50 mg/mmoL; and prednisone or prednisone-equivalent dose tapered to 10 mg per day.
End of short-term period (Day 365) to termination of the long-term extension period
Number of Participants Achieving Patient Response of Complete or Partial Response, Based on the June 2010 Food and Drug Administration Guidance Document for Lupus Nephritis
Periodo de tiempo: At Day 365 (end of Short-term Period) and Day 645
Patient response=complete, partial, or no response. Complete response=serum creatinine (SCr) normal, inactive urinary sediment, no cellular casts, urinary protein/creatinine (UPCR) ratio<56.5 mg/mmol. Partial response=SCr normal or ≤25% above baseline value, RBCs at reference range, UPCR <56.5 mg/mmoL OR ≥50% improvement in UPCR with one of the following: UPCR <113 or <339 mg/mmoL, based on the baseline ratio. No response=Not achieving complete or partial response criteria.
At Day 365 (end of Short-term Period) and Day 645
Mean Change From Baseline in SLICC/ACR Damage Index
Periodo de tiempo: Day 365 to termination of the long-term extension phase
SLICC=Systemic Lupus International Collaborating Clinics; ACR=American College of Rheumatology. The SLICC/ACR Damage Index measures organ damage (nonreversible change, unrelated to active inflammation) occurring since onset of lupus, ascertained by clinical assessment and present for at least 6 months unless otherwise stated. The index assesses 47 items in 12 systems: Ocular, Neuropsychiatric, Renal, Pulmonary, Cardiovascular, Gastrointestinal, Peripheral Vascular, Musculoskeletal, Skin, Premature Gonadal Failure, Diabetes, Malignancy. Scores range from 0 to 2, and the same lesion cannot be scored twice. If damage is noted for a particular item, it is scored 1. No damage is scored 0. Some items may score 2 points if they occur more than once, so that the maximum possible score is 47. Scores can only increase with time, but scores rarely reach over 12. It is usually completed (or updated) yearly.
Day 365 to termination of the long-term extension phase
Number of Participants With Death, Serious Adverse Events (SAE), Treatment-related Adverse Events SAEs, Discontinuations Due to SAEs, Adverse Events (AEs), Treatment-related AEs, and Discontinuations Due to AEs During Long-term Extension Period
Periodo de tiempo: From start of study drug in long-term period (Day 365) to up to 56 days after the last dose of the long-term extension (LTE). Deaths in LTE reported to >56 days post last dose.
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. Related=possibly, probably, or certainly related to and of unknown relationship to study drug.
From start of study drug in long-term period (Day 365) to up to 56 days after the last dose of the long-term extension (LTE). Deaths in LTE reported to >56 days post last dose.
Number of Participants With a Treatment-emergent Seropositive Result During the Long-term Extension Period
Periodo de tiempo: Day 365 to end of long-term extension period
Collected in at least 1 sample. Assessment includes immunogenicity (detection of serum antibodies which bind to CTLA4-Ig in the in vitro assays) and exposure to corticosteroids
Day 365 to end of long-term extension period
Number of Participants Achieving Renal Response
Periodo de tiempo: At Day 365 (end of short-term period) and Day 645
Renal response=serum creatinine level ≤25% above baseline value and greater than or equal to 50% improvement in the urine protein/creatinine ratio with 1 of the following: urine protein/creatinine ratio (UPCR) <113 mg/mmol, if the baseline ratio was <= 339 mg/mmol OR UPCR <339 mg/mmol,if the baseline ratio >339 mg/mmol.
At Day 365 (end of short-term period) and Day 645
Number of Participants With Marked Laboratory Abnormalities During the Long-term Extension Period
Periodo de tiempo: From start of study drug on Day 365 up to 56 days after last dose in the long-term extension period
preRX=pretreatment; LLN=lower limit of normal; ULN=upper limit of normal. Hemoglobin (g/dL): >3g/dL decrease from preRX value. Hematocrit(%): <0.75*preRX. Erythrocytes (*10^6 c/uL): <0.75*preRX. Platelet count (*10^9 c/L): <0.67*LLN, or >1.5*ULN, or if preRX <LLN, use <0.5*preRX and <100,000/mm^3. Leukocytes (*10^3 c/uL): <0.75*LLN or >1.25*ULN, or if preRX <LLN, use <0.8* preRX or >ULN; if preRX>ULN, use >1.2*preRX or <LLN. Neutrophils + Bands (absolute) (*10^3 c/uL): If value <1.0*10^3 or if value >7.50*10^3 c/uL. Monocytes (absolute) (*10^3 c/uL): If value >2000/mm^3. Basophils (absolute)(*10^3 c/uL): If value >.750*10^3 c/uL. Eosinophils (absolute) (*10^3 c/uL): If value >.750*10^3 c/uL. ALP (U/L): >2*ULN, or if preRX>ULN, use >3* preRX. AST (U/L): >3*ULN, or if preRX>ULN, use >4*preRX. ALT (U/L): >3*ULN, or if preRX>ULN, use >4*preRX. GGT (U/L):>2*ULN, or if preRX >ULN, use >3*preRX. Bilirubin, total (mg/dL): >2*ULN, or if preRX>ULN, use >4*preRX. BUN (mg/dL): >1.5*preRX.
From start of study drug on Day 365 up to 56 days after last dose in the long-term extension period
Number of Participants With Marked Laboratory Abnormalities During the Long-term Extension Period (Continued)
Periodo de tiempo: From start of study drug on Day 365 up to 56 days after last dose in the long-term extension period
LLN=lower limit of normal; ULN=upper limit of normal; preRX=pretreatment. Sodium, serum (mEq/L): <0.95*LLN or >1.05*ULN, or if preRX<LLN, use <0.95*preRX or >ULN if preRX>ULN, use >1.05*preRX or <LLN. Potassium, serum (mEq/L): <0.9* LLN or >1.1*ULN, or if preRX <LLN, use <0.9*preRX or >ULN if preRX>ULN, use >1.1*preRX or <LLN. Chloride, serum (mEq/L): <0.9*LLN or >1.1*ULN, or if preRX<LLN, use <0.9*preRX or >ULN. Calcium, total (mg/dL): <0.8*LLN or >1.2*ULN, or if preRX<LLN, use <0.75*preRX or >ULN if preRX>ULN, use >1.25*preRX or <LLN. Glucose, serum (mg/dL): <65 mg/dL, or >220 mg/dL. Glucose, fasting serum (mg/dL): <0.8*LLN or >1.5*ULN, or if preRX <LLN, use <0.8*preRX or >ULN if preRX>ULN, use >2.0*preRX or <LLN. Albumin (g/dL): <0.9*LLN, or if preRX <LLN, use <0.75*preRX. Cholesterol, total (mg/dL): >2*preRX. Triglycerides (mg/dL): >=2.5*ULN, or if preRX>ULN, use >=2.5*preRX. Triglycerides, fasting (mg/dL): >=2*ULN, or if preRX>ULN, use >2.0*preRX.
From start of study drug on Day 365 up to 56 days after last dose in the long-term extension period
Number of Participants With Marked Laboratory Abnormalities During the Long-term Extension Period (Continued)
Periodo de tiempo: From start of study drug on Day 365 to up to 56 days after last dose in the long-term extension period
preRX=pretreatment. Protein, urine: If missing preRX, use >=2, or if value >=4, or if preRX =0 or 0.5, use >=2, or if preRX=1, use >=3, or if preRX=2 OR 3 then use >=4. Glucose, urine: If missing preRX, use >=2, or if value >=4, or if preRX=0 or 0.5, use >=2, or if preRX=1, use >=3, or if preRX=2 or 3, use >=4. Blood, urine: If missing preRX, use >=2, or if value >=4, or if preRX =0 or 0.5, use >=2, or if preRX=1, use >=3, or if preRX=2 or 3, use >=4. Leukocyte esterase, urine: If missing preRX, use >=2, or if value >=4, or if preRX=0 or 0.5, use >=2, or if preRX=1, use >=3, or if preRX=2 or 3, use >=4.
From start of study drug on Day 365 to up to 56 days after last dose in the long-term extension period

Otras medidas de resultado

Medida de resultado
Medida Descripción
Periodo de tiempo
Number of Participants Achieving Patient Response (PR) at Month 12 During the Short-term Period
Periodo de tiempo: Month 12

PR is either CRR, Partial Renal Response(PRR),or no Response(NR).

CRR= Serum creatinine(SC)is normal, Inactive urinary sediment, No cellular casts, Urinary protein/creatinine (UPCR) ratio <56.5 mg/mmoL; PRR= SC is normal OR SC not >25% above BL, RBCs at reference range, UPCR <56.5 mg/mmoL OR ≥50% improvement in UPCR with one of the following: UPCR <113 or <339 mg/mmoL, based on the BL ratio; NR= Not achieving either a CRR or a PRR. Participants achieved response if criteria at both months 11 and 12 (Days 337 and 365) were met. Participants who Early discontinuations were categorized as NR.
Month 12

Colaboradores e Investigadores

Aquí es donde encontrará personas y organizaciones involucradas en este estudio.

Patrocinador

Bristol-Myers Squibb

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

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 junio de 2007

Finalización primaria (Actual)

1 de septiembre de 2010

Finalización del estudio (Actual)

1 de agosto de 2011

Fechas de registro del estudio

Enviado por primera vez

1 de febrero de 2007

Primero enviado que cumplió con los criterios de control de calidad

1 de febrero de 2007

Publicado por primera vez (Estimar)

2 de febrero de 2007

Actualizaciones de registros de estudio

Última actualización publicada (Estimar)

20 de marzo de 2015

Última actualización enviada que cumplió con los criterios de control de calidad

3 de marzo de 2015

Última verificación

1 de marzo de 2015

Más información

Términos relacionados con este estudio

Términos MeSH relevantes adicionales

Otros números de identificación del estudio

  • IM101-075

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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