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Study Comparing the Safety and Efficacy of Belatacept With That of Cyclosporine in Patients With a Transplanted Kidney

27 ноября 2013 г. обновлено: 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).

Обзор исследования

Статус

Завершенный

Условия

Вмешательство/лечение

Тип исследования

Интервенционный

Регистрация (Действительный)

230

Фаза

  • Фаза 2

Контакты и местонахождение

В этом разделе приведены контактные данные лиц, проводящих исследование, и информация о том, где проводится это исследование.

Места учебы

  • Соединенные Штаты
    • California
      • San Francisco, California, Соединенные Штаты, 94143-0001
        • Univ. of Calif. - San Francisco
    • Georgia
      • Atlanta, Georgia, Соединенные Штаты, 30322
        • Emory Univ. School of Medicine
    • Maryland
      • Baltimore, Maryland, Соединенные Штаты, 21205
        • Johns Hopkins University
    • Massachusetts
      • Boston, Massachusetts, Соединенные Штаты, 02114
        • Massachusetts General Hospital
    • Minnesota
      • Rochester, Minnesota, Соединенные Штаты, 55905
        • Mayo Clinic
    • Nebraska
      • Omaha, Nebraska, Соединенные Штаты, 68198-1002
        • Univ. of Nebraska Medical Center
    • New Jersey
      • Livingston, New Jersey, Соединенные Штаты, 07039
        • Saint Barnabas Medical Center
    • New York
      • New York, New York, Соединенные Штаты, 10029-6574
        • Mount Sinai Medical Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, Соединенные Штаты, 19104
        • Univ. of Pennsylvania
    • South Carolina
      • Charleston, South Carolina, Соединенные Штаты, 29425
        • Medical Univ. of South Carolina
    • Texas
      • Dallas, Texas, Соединенные Штаты, 75246
        • Baylor Univ. Medical Center
    • Wisconsin
      • Madison, Wisconsin, Соединенные Штаты, 53792-7375
        • Univ. of Wisconsin

Критерии участия

Исследователи ищут людей, которые соответствуют определенному описанию, называемому критериям приемлемости. Некоторыми примерами этих критериев являются общее состояние здоровья человека или предшествующее лечение.

Критерии приемлемости

Возраст, подходящий для обучения

18 лет и старше (Взрослый, Пожилой взрослый)

Принимает здоровых добровольцев

Нет

Полы, имеющие право на обучение

Все

Описание

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.

Учебный план

В этом разделе представлена ​​подробная информация о плане исследования, в том числе о том, как планируется исследование и что оно измеряет.

Как устроено исследование?

Детали дизайна

  • Основная цель: Профилактика
  • Распределение: Рандомизированный
  • Интервенционная модель: Параллельное назначение
  • Маскировка: Нет (открытая этикетка)

Оружие и интервенции

Группа участников / Армия
Вмешательство/лечение
Экспериментальный: 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.
Лекарство: Belatacept
Solution, intravenous
Другие имена:
  • LEA29Y, BMS-224818
Лекарство: Mycophenolate mofetil (MMF)
Oral, capsule
Лекарство: Corticosteroids
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
Экспериментальный: 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.
Лекарство: Belatacept
Solution, intravenous
Другие имена:
  • LEA29Y, BMS-224818
Лекарство: Mycophenolate mofetil (MMF)
Oral, capsule
Лекарство: Corticosteroids
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
Экспериментальный: 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.
Лекарство: Mycophenolate mofetil (MMF)
Oral, capsule
Лекарство: Corticosteroids
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
Лекарство: Cyclosporine
Oral, capsule
Другие имена:
  • The cyclosporine used in this study will be in the modified formulation with enhanced bioavailability.

Что измеряет исследование?

Первичные показатели результатов

Мера результата
Мера Описание
Временное ограничение
Number of Participants With an Episode of Clinically-suspected and Biopsy-proven Acute Rejection (CSPAR)
Временное ограничение: By Month 6 posttransplant (From Day 1 to Month 6)
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.
By Month 6 posttransplant (From Day 1 to Month 6)

Вторичные показатели результатов

Мера результата
Мера Описание
Временное ограничение
Percentage of Participants With Biopsy-proven Acute Rejection (BPAR) Through Months 6 and 12
Временное ограничение: Through Months 6 and 12 posttransplant (From Day 1 to Months 6 and 12)
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.
Through Months 6 and 12 posttransplant (From Day 1 to Months 6 and 12)
Percentage of Participants With Biopsy-proven Acute Rejection (BPAR) or Who Received Treatment for Acute Rejection
Временное ограничение: By Months 3, 6, and 12 posttransplant (Day 1 to Months 3, 6, and 12)
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).
By Months 3, 6, and 12 posttransplant (Day 1 to Months 3, 6, and 12)
Percentage of Participants With Acute Rejection or Presumed Acute Rejection (PAR)
Временное ограничение: By Months 6 and 12 posttransplant (Day 1 to Months 6 and 12)
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.
By Months 6 and 12 posttransplant (Day 1 to Months 6 and 12)
Percentage of Participants Who Had Chronic Allograft Nephropathy
Временное ограничение: By Months 6 and 12 posttransplant (Day 1 to Months 6 and 12)
Based on postbaseline biopsies
By Months 6 and 12 posttransplant (Day 1 to Months 6 and 12)
Mean Iohexol Clearance
Временное ограничение: By Months 1, 6, and 12 posttransplant (Day 1 to Months 1, 6, and 12)
Iohexol, a true glomerular filtration marker, is used to measure glomerular filtration rate.
By Months 1, 6, and 12 posttransplant (Day 1 to Months 1, 6, and 12)
Percentage of Participants Who Used Antihypertensive Medication
Временное ограничение: By Months 6 and 12 posttransplant (Day 1 to Months 6 and 12)
Hypertension is defined as diastolic blood pressure ≥90 mm Hg and/or systolic blood pressure ≥140 mm Hg
By Months 6 and 12 posttransplant (Day 1 to Months 6 and 12)
Number of Participants With Hypertension
Временное ограничение: By Months 6 and 12 posttransplant (Day 1 to Months 6 and 12)
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.
By Months 6 and 12 posttransplant (Day 1 to Months 6 and 12)
Mean LDL Cholesterol, HDL Cholesterol, Total Cholesterol, Triglyceride, and Non-HDL Levels
Временное ограничение: By Months 1, 6, and 12 posttransplant (Day 1 to Months 1, 6, and 12)
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.
By Months 1, 6, and 12 posttransplant (Day 1 to Months 1, 6, and 12)
Number of Participants With Posttransplant Diabetes Mellitus
Временное ограничение: By Months 1, 3, 6, 9, and 12 posttransplant (Day 1 to Months 1, 3, 6, 9, and 12 )
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
By Months 1, 3, 6, 9, and 12 posttransplant (Day 1 to Months 1, 3, 6, 9, and 12 )

Другие показатели результатов

Мера результата
Мера Описание
Временное ограничение
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
Временное ограничение: Day 1 (posttransplant) continuously to 56 days following last dose of study medication
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.
Day 1 (posttransplant) continuously to 56 days following last dose of study medication
Number of Participants Meeting Marked Abnormality Criteria for Select Hemolytic, Blood Chemistry, and Urinalysis Laboratory Test Results
Временное ограничение: Days 8 and Months 1, 3, 6, 9, and 12 posttransplant (from Day 1)
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.
Days 8 and Months 1, 3, 6, 9, and 12 posttransplant (from Day 1)

Соавторы и исследователи

Здесь вы найдете людей и организации, участвующие в этом исследовании.

Спонсор

Bristol-Myers Squibb

Даты записи исследования

Эти даты отслеживают ход отправки отчетов об исследованиях и сводных результатов на сайт ClinicalTrials.gov. Записи исследований и сообщаемые результаты проверяются Национальной медицинской библиотекой (NLM), чтобы убедиться, что они соответствуют определенным стандартам контроля качества, прежде чем публиковать их на общедоступном веб-сайте.

Изучение основных дат

Начало исследования

1 марта 2001 г.

Первичное завершение (Действительный)

1 января 2004 г.

Завершение исследования (Действительный)

1 июля 2012 г.

Даты регистрации исследования

Первый отправленный

3 мая 2002 г.

Впервые представлено, что соответствует критериям контроля качества

3 мая 2002 г.

Первый опубликованный (Оценивать)

6 мая 2002 г.

Обновления учебных записей

Последнее опубликованное обновление (Оценивать)

13 января 2014 г.

Последнее отправленное обновление, отвечающее критериям контроля качества

27 ноября 2013 г.

Последняя проверка

1 ноября 2013 г.

Дополнительная информация

Термины, связанные с этим исследованием

Ключевые слова

Дополнительные соответствующие термины MeSH

Другие идентификационные номера исследования

  • IM103-100

Эта информация была получена непосредственно с веб-сайта clinicaltrials.gov без каких-либо изменений. Если у вас есть запросы на изменение, удаление или обновление сведений об исследовании, обращайтесь по адресу register@clinicaltrials.gov. Как только изменение будет реализовано на clinicaltrials.gov, оно будет автоматически обновлено и на нашем веб-сайте. .

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