Study Comparing the Safety and Efficacy of Belatacept With That of Cyclosporine in Patients With a Transplanted Kidney
2013年11月27日 更新者：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).
調査の概要
状態
完了
研究の種類
介入
入学 (実際)
230
段階
- フェーズ2
連絡先と場所
このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。
研究場所
-
-
California
-
San Francisco、California、アメリカ、94143-0001
- Univ. of Calif. - San Francisco
-
-
Georgia
-
Atlanta、Georgia、アメリカ、30322
- Emory Univ. School of Medicine
-
-
Maryland
-
Baltimore、Maryland、アメリカ、21205
- Johns Hopkins University
-
-
Massachusetts
-
Boston、Massachusetts、アメリカ、02114
- Massachusetts General Hospital
-
-
Minnesota
-
Rochester、Minnesota、アメリカ、55905
- Mayo Clinic
-
-
Nebraska
-
Omaha、Nebraska、アメリカ、68198-1002
- Univ. of Nebraska Medical Center
-
-
New Jersey
-
Livingston、New Jersey、アメリカ、07039
- Saint Barnabas Medical Center
-
-
New York
-
New York、New York、アメリカ、10029-6574
- Mount Sinai Medical Center
-
-
Pennsylvania
-
Philadelphia、Pennsylvania、アメリカ、19104
- Univ. of Pennsylvania
-
-
South Carolina
-
Charleston、South Carolina、アメリカ、29425
- Medical Univ. of South Carolina
-
-
Texas
-
Dallas、Texas、アメリカ、75246
- Baylor Univ. Medical Center
-
-
Wisconsin
-
Madison、Wisconsin、アメリカ、53792-7375
- Univ. of Wisconsin
-
-
参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
適格基準
就学可能な年齢
18年歳以上 (大人、高齢者)
健康ボランティアの受け入れ
いいえ
受講資格のある性別
全て
説明
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.
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：防止
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
実験的：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.
|
Solution, intravenous
他の名前：
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
|
|
実験的：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.
|
Solution, intravenous
他の名前：
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
|
|
実験的：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
他の名前：
|
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Number of Participants With an Episode of Clinically-suspected and Biopsy-proven Acute Rejection (CSPAR)
時間枠：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)
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Percentage of Participants With Biopsy-proven Acute Rejection (BPAR) Through Months 6 and 12
時間枠：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
時間枠：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)
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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 )
|
その他の成果指標
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
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
時間枠：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
時間枠：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)
|
協力者と研究者
ここでは、この調査に関係する人々や組織を見つけることができます。
スポンサー
研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始
2001年3月1日
一次修了 (実際)
2004年1月1日
研究の完了 (実際)
2012年7月1日
試験登録日
最初に提出
2002年5月3日
QC基準を満たした最初の提出物
2002年5月3日
最初の投稿 (見積もり)
2002年5月6日
学習記録の更新
投稿された最後の更新 (見積もり)
2014年1月13日
QC基準を満たした最後の更新が送信されました
2013年11月27日
最終確認日
2013年11月1日
詳しくは
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。