Эта страница была переведена автоматически, точность перевода не гарантируется. Пожалуйста, обратитесь к английской версии для исходного текста.

A Study to Assess the Efficacy and Safety of Alefacept in Kidney Transplant Recipients

5 января 2016 г. обновлено: Astellas Pharma Inc

Efficacy and Safety of Alefacept in Combination With Tacrolimus, Mycophenolate Mofetil and Steroids in de Novo Kidney Transplantation - a Multicenter, Randomized, Double-Blind, Placebo Controlled, Parallel Group Study

The purpose of this study is to determine whether alefacept is effective and well tolerated when used with a combination of tacrolimus, mycophenolate mofetil and steroids versus a combination therapy of placebo, tacrolimus and steroids in the prevention of kidney transplant rejection.

Обзор исследования

Статус

Завершенный

Условия

Вмешательство/лечение

Тип исследования

Интервенционный

Регистрация (Действительный)

218

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

  • Австрия
      • Vienna, Австрия, 1090
  • Бельгия
      • Bruxelles, Бельгия, 1070
      • Bruxelles, Бельгия, 1200
      • Gent, Бельгия, 9000
      • Leuven, Бельгия, 3000
      • Liege, Бельгия, 4000
  • Венгрия
      • Budapest, Венгрия, 1082
  • Германия
      • Bochum, Германия, 44892
      • Regensburg, Германия, 93053
  • Испания
      • Barcelona, Испания, 8036
      • Llobregat, Испания, 8907
      • Madrid, Испания, 28041
      • Malaga, Испания, 29010
      • Santander, Испания, 39008
  • Италия
      • Bologna, Италия, 40138
      • Padova, Италия, 35128
      • Rome, Италия, 00168
      • Siena, Италия, 53100
  • Нидерланды
      • Maastricht, Нидерланды, 6229
  • Польша
      • Bydgoszcz, Польша, 85-094
      • Poznan, Польша, 60-479
      • Szczecin, Польша, 70-111
  • Соединенное Королевство
      • Manchester, Соединенное Королевство, M13 9WL
  • Франция
      • Creteil, Франция, 94010
      • Le Kremlin Bicetre Cedex, Франция, 94275
      • Montpellier, Франция, 34295
      • Nantes Cedex 1, Франция, 44093
      • Nice Cedex 1, Франция, 6002
      • Paris, Франция, 75475
      • Toulouse Cedex, Франция, 31054
  • Чешская Республика
      • Praha, Чешская Республика, 140 21
  • Швеция
      • Goteborg, Швеция, 41345
      • Uppsala, Швеция, 75185

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

От 18 лет до 64 года (Взрослый)

Принимает здоровых добровольцев

Нет

Полы, имеющие право на обучение

Все

Описание

Inclusion Criteria:

  • Subject with end stage kidney disease who is a suitable candidate for primary kidney transplantation or retransplantation
  • Male or female subject at least 18 years of age and younger than 65 years
  • Subject receiving a kidney transplant from a non-human leucocyte antigen (HLA) identical living donor or deceased HLA identical/non-HLA identical donor between 5 and 59 years of age with compatible ABO blood type (Blood group system A, B, AB and 0)

Exclusion Criteria:

  • Subject has a panel reactivity antibody grade > 20% in the previous 6 months and/or had had a previous graft survival shorter than 1 year due to immunological reasons
  • Subject received a kidney transplant from a non-heart beating donor
  • Subject has received a kidney transplant from a 50 - 59 year old donor with two of the following three factors: history of hypertension, cerebrovascular accident as cause of death, final pre-procurement serum creatinine > 1.5 mg/dL (united network for organ sharing [UNOS] expanded criteria donor)
  • Cold ischemia time of the donor kidney is ≥ 30 hours

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: Четырехместный

Оружие и интервенции

Группа участников / Армия
Вмешательство/лечение
Плацебо Компаратор: Placebo
Participants received placebo administered intra-operatively as an intravenous (IV) bolus on Day 0, another IV bolus on Day 3 and weekly subcutaneous injections thereafter for 12 weeks. Participants also received tacrolimus, mycophenolate mofetil (MMF) and steroid treatment.
Лекарство: placebo
IV and subcutaneous injection
Лекарство: Tacrolimus
The initial daily dose was 0.2 mg/kg orally given in 2 doses commencing 24 hours after completion of surgery.
Лекарство: Mycophenolate Mofetil
Mycophenolic mofetil was administered as 750 mg twice per day orally
Лекарство: Steroids

Methylprednisolone or equivalent:

Day 0: 500 - 1000 mg IV bolus Day 1: 125 - 250 mg IV bolus

Prednisone or equivalent:

Days 2 - 14: 20 - 30 mg orally Days 15 - 28: 10 - 20 mg orally Days 29 - 60: 10 - 15 mg orally Days 61 onwards: 5 - 10 mg orally
Экспериментальный: Alefacept
Participants received 7.5 mg alefacept administered intra-operatively as an IV bolus on Day 0, another 7.5 mg IV bolus on Day 3, and weekly subcutaneous injections of 15 mg alefacept thereafter for 12 weeks. Participants also received tacrolimus, MMF and steroid treatment.
Лекарство: Tacrolimus
The initial daily dose was 0.2 mg/kg orally given in 2 doses commencing 24 hours after completion of surgery.
Лекарство: Mycophenolate Mofetil
Mycophenolic mofetil was administered as 750 mg twice per day orally
Лекарство: Steroids

Methylprednisolone or equivalent:

Day 0: 500 - 1000 mg IV bolus Day 1: 125 - 250 mg IV bolus

Prednisone or equivalent:

Days 2 - 14: 20 - 30 mg orally Days 15 - 28: 10 - 20 mg orally Days 29 - 60: 10 - 15 mg orally Days 61 onwards: 5 - 10 mg orally

Лекарство: Alefacept
IV and subcutaneous injection
Другие имена:
  • Амевив

Что измеряет исследование?

Первичные показатели результатов

Мера результата
Мера Описание
Временное ограничение
Percentage of Participants With Biopsy-confirmed Acute T-cell Mediated Rejection at Month 6 Assessed by Local Review
Временное ограничение: 6 months

Biopsies were graded by the clinical site pathologist.according to the Banff 97/05 updated histological classification:

  • Grade IA: significant interstitial infiltration (>25% parenchyma affected) and foci of moderate tubulitis;
  • Grade IB: significant interstitial infiltration (>25% parenchyma affected) and foci of severe tubulitis;
  • Grade IIA: mild to moderate intimal arteritis;
  • Grade IIB: severe intimal arteritis comprising >25% of the luminal area;
  • Grade III: "transmural" arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells with accompanying lymphocyte inflammation.

A biopsy confirmed acute rejection was an event of suspected acute rejection confirmed by a graft biopsy result of Banff grade ≥ 1.

The Kaplan-Meier estimate of biopsy-confirmed acute T-cell mediated rejection within the first 6 months following transplantation is reported. Participants lost to follow-up or with missing outcomes were censored at their last follow up visit.
6 months

Вторичные показатели результатов

Мера результата
Мера Описание
Временное ограничение
Percentage of Participants With Biopsy Confirmed Antibody-Mediated Acute Rejection at Month 6
Временное ограничение: 6 months

Biopsies were graded by the clinical site pathologist.according to the Banff 97/05 updated histological classification:

Acute antibody-mediated rejection - documented anti-donor antibody ('suspicious for' if antibody not demonstrated):

  • Grade I: acute tubular necrosis-like - complement split product positive (C4d+), minimal inflammation;
  • Grade II: capillary-margination and/or thromboses, C4d+
  • Grade III: arterial - v3, C4d+.

A biopsy confirmed acute rejection was an event of suspected acute rejection confirmed by a graft biopsy result of Banff grade ≥ 1.

The Kaplan-Meier estimate of biopsy-confirmed antibody-mediated acute rejection within the first 6 months following transplantation is reported. Participants lost to follow-up or with missing outcomes were censored at their last follow up visit.
6 months
Percentage of Participants With Biopsy Confirmed Acute Rejection (T-Cell Mediated or Antibody Mediated) at Month 6
Временное ограничение: 6 months

Biopsies were graded by the clinical site pathologist.according to the Banff 97/05 updated histological classification. A biopsy confirmed acute rejection was an event of suspected acute rejection confirmed by a graft biopsy result of Banff grade ≥ 1.

The Kaplan-Meier estimate of biopsy-confirmed acute T-cell mediated or antibody-mediated rejection within the first 6 months following transplantation is reported. Participants lost to follow-up or with missing outcomes were censored at their last follow up visit.
6 months
Percentage of Participants With Biopsy Confirmed Acute Mixed T-Cell Mediated and Antibody-Mediated Rejection at Month 6
Временное ограничение: 6 months

Biopsies were graded by the clinical site pathologist.according to the Banff 97/05 updated histological classification. A biopsy confirmed acute rejection was an event of suspected acute rejection confirmed by a graft biopsy result of Banff grade ≥ 1.

The Kaplan-Meier estimate of biopsy-confirmed acute mixed T-cell mediated and antibody-mediated rejections within the first 6 months following transplantation is reported. Participants lost to follow-up or with missing outcomes were censored at their last follow up visit.
6 months
Percentage of Participants With Acute Rejection Diagnosed by Signs and Symptoms at Month 6
Временное ограничение: 6 months
Acute rejection diagnosed by signs and symptoms, including biopsy-confirmed or suspected (not confirmed by biopsy - i.e. no biopsy was performed or biopsy did not confirm an acute T-cell mediated rejection). The Kaplan-Meier estimate of acute rejection diagnosed by signs and symptoms within the first 6 months following transplantation is reported. Participants lost to follow-up or with missing outcomes were censored at their last follow up visit.
6 months
Percentage of Participants With Clinically Treated Acute Rejection at Month 6
Временное ограничение: 6 months
Patients who received immunosuppressive medications for the treatment of suspected or biopsy-confirmed acute rejections were considered to have a clinically-treated acute rejection. The Kaplan-Meier estimate of clinically treated acute rejection within the first 6 months following transplantation is reported. Participants lost to follow-up or with missing outcomes were censored at their last follow-up visit.
6 months
Percentage of Participants With Steroid-resistant Acute Rejection at Month 6
Временное ограничение: 6 months

A steroid-resistant acute rejection is defined as a rejection episode which did not resolve following treatment with corticosteroids. In the case that a rejection episode was not treated with corticosteroids first but only with antibodies, it was included in this category.

The Kaplan-Meier estimate of steroid-resistant acute rejection within the first 6 months following transplantation is reported. Participants lost to follow-up or with missing outcomes were censored at their last follow up visit.
6 months
Percentage of Participants With Biopsy-Confirmed Acute T-cell Mediated Rejection as Assessed by Central Review at Month 6
Временное ограничение: 6 months

Biopsies were graded by the central reviewer according to the Banff 97/05 updated histological classification. A biopsy confirmed acute rejection was an event of suspected acute rejection confirmed by a graft biopsy result of Banff grade ≥ 1.

The Kaplan-Meier estimate of biopsy-confirmed acute T-cell mediated rejection within the first 6 months following transplantation is reported. Participants lost to follow-up or with missing outcomes were censored at their last follow up visit.
6 months
Patient Survival
Временное ограничение: 6 months
Patient survival is any participant known to be alive at Month 6. The Kaplan-Meier estimate of patient survival within the first 6 months following transplantation is reported. Participants lost to follow-up were censored at the time of last assessment.
6 months
Graft Survival
Временное ограничение: 6 months

Graft survival was defined as any participant who was known to have a functioning graft (i.e., not graft loss) at 6 months. Graft loss is defined as re-transplantation, nephrectomy, death or as dialysis ongoing at end of study or at discontinuation of the participant unless superseded by follow-up information.

The Kaplan-Meier estimate of graft survival within the first 6 months following transplantation is reported. Participants lost to follow-up were censored at the time of last assessment.
6 months
Maximum Histological Grade of All Biopsies After Local Review
Временное ограничение: 6 months

The grade of acute rejection was classified according to Banff 97/05 updated version. If a patient had more than 1 rejection episode, the episode with the most severe grade was used.

Acute T-cell mediated rejection:

  • Grade IA: significant interstitial infiltration (>25% parenchyma affected) and foci of moderate tubulitis;
  • Grade IB: significant interstitial infiltration (>25% parenchyma affected) and foci of severe tubulitis;
  • Grade IIA: mild to moderate intimal arteritis;
  • Grade IIB: severe intimal arteritis comprising >25% of the luminal area;
  • Grade III: "transmural" arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells with accompanying lymphocyte inflammation.

Acute antibody-mediated rejection:

  • Grade I: acute tubular necrosis-like - complement split product positive (C4d+), minimal inflammation;
  • Grade II: capillary-margination and/or thromboses, C4d+
  • Grade III: arterial - v3, C4d+.
6 months
Percentage of Participants With Anti-Lymphocyte Antibody Therapy for Treatment of Rejection at Month 6
Временное ограничение: 6 months
The Kaplan-Meier estimate of anti-lymphocyte antibody therapy for acute rejection (clinically-treated or biopsy-confirmed) within the first 6 months following transplantation is reported. Participants lost to follow-up or with missing outcomes were censored at their last follow-up visit.
6 months
Change From Month 1 in Serum Creatinine
Временное ограничение: Month 1, 3, and 6
Month 1, 3, and 6
Change From Month 1 in Glomerular Filtration Rate (GFR)
Временное ограничение: Month 1, 3, and 6
The GFR was calculated using the Modification of Diet in Renal Disease (MDRD) formula.
Month 1, 3, and 6
Change From Month 1 in Creatinine Clearance
Временное ограничение: Month 1, 3, and 6
The creatinine clearance was calculated according to the Cockcroft-Gault formula.
Month 1, 3, and 6
GFR Measured by Iothalamate Clearance at Month 6
Временное ограничение: Month 6
GFR measured using the iothalamate clearance method and determined by a central laboratory.
Month 6
Percentage of Participants With Efficacy Failure at Month 6
Временное ограничение: 6 months

Efficacy failure is defined as death, graft loss, biopsy-confirmed acute T-cell mediated rejection assessed by local reading or lost to follow-up.

The Kaplan-Meier estimate of efficacy failure within the first 6 months following transplantation is reported.
6 months
Percentage of Participants With Delayed Graft Function
Временное ограничение: 1 week
Delayed graft function was defined as the requirement for dialysis within the first week post-transplant.
1 week
Percentage of Participants With Treatment Failure at Month 6
Временное ограничение: 6 months
Treatment failure is defined as efficacy failure (death, graft loss, biopsy-confirmed acute T-cell mediated rejection assessed by local reading, lost to follow-up) or early discontinuation of alefacept/placebo at any time (during the 12-week administration period) for any reason. The Kaplan-Meier estimate of treatment failure within the first 6 months following transplantation is reported. Participants lost to follow-up or with missing outcomes were censored at their last follow-up visit.
6 months
Number of Participants With Adverse Events
Временное ограничение: 6 Months

Causally related was defined as adverse events (AEs) assessed by the Investigator as possibly or probably related to study drug or records where the relationship was missing.

A serious adverse event (SAE) was any untoward medical occurrence that, at any dose:

  • Resulted in death.
  • Was life-threatening.
  • Resulted in persistent or significant disability/incapacity.
  • Resulted in congenital anomaly or birth defect.
  • Required patient hospitalization or led to prolongation of hospitalization
  • Was considered a medically important event.

All rejections and any BK virus, Epstein Barr virus and/or cytomegalovirus infection had to be reported as an SAE
6 Months

Соавторы и исследователи

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

Спонсор

Astellas Pharma Inc

Публикации и полезные ссылки

Лицо, ответственное за внесение сведений об исследовании, добровольно предоставляет эти публикации. Это может быть что угодно, связанное с исследованием.

Полезные ссылки

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 декабря 2007 г.

Первичное завершение (Действительный)

1 сентября 2009 г.

Завершение исследования (Действительный)

1 сентября 2009 г.

Даты регистрации исследования

Первый отправленный

6 февраля 2008 г.

Впервые представлено, что соответствует критериям контроля качества

6 февраля 2008 г.

Первый опубликованный (Оценивать)

18 февраля 2008 г.

Обновления учебных записей

Последнее опубликованное обновление (Оценивать)

4 февраля 2016 г.

Последнее отправленное обновление, отвечающее критериям контроля качества

5 января 2016 г.

Последняя проверка

1 января 2016 г.

Дополнительная информация

Термины, связанные с этим исследованием

Ключевые слова

Дополнительные соответствующие термины MeSH

Другие идентификационные номера исследования

  • 0485-CL-E201
  • 2007-002092-14 (Номер EudraCT)

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. .

Подписаться