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

27. listopadu 2013 aktualizováno: 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).

Přehled studie

Postavení

Dokončeno

Podmínky

Intervence / Léčba

Typ studie

Intervenční

Zápis (Aktuální)

230

Fáze

  • Fáze 2

Kontakty a umístění

Tato část poskytuje kontaktní údaje pro ty, kteří studii provádějí, a informace o tom, kde se tato studie provádí.

Studijní místa

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

Kritéria účasti

Výzkumníci hledají lidi, kteří odpovídají určitému popisu, kterému se říká kritéria způsobilosti. Některé příklady těchto kritérií jsou celkový zdravotní stav osoby nebo předchozí léčba.

Kritéria způsobilosti

Věk způsobilý ke studiu

18 let a starší (Dospělý, Starší dospělý)

Přijímá zdravé dobrovolníky

Ne

Pohlaví způsobilá ke studiu

Všechno

Popis

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.

Studijní plán

Tato část poskytuje podrobnosti o studijním plánu, včetně toho, jak je studie navržena a co studie měří.

Jak je studie koncipována?

Detaily designu

  • Primární účel: Prevence
  • Přidělení: Randomizované
  • Intervenční model: Paralelní přiřazení
  • Maskování: Žádné (otevřený štítek)

Zbraně a zásahy

Skupina účastníků / Arm
Intervence / Léčba
Experimentální: 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.
Lék: Belatacept
Solution, intravenous
Ostatní jména:
  • LEA29Y, BMS-224818
Lék: Mycophenolate mofetil (MMF)
Oral, capsule
Lék: 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
Experimentální: 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.
Lék: Belatacept
Solution, intravenous
Ostatní jména:
  • LEA29Y, BMS-224818
Lék: Mycophenolate mofetil (MMF)
Oral, capsule
Lék: 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
Experimentální: 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.
Lék: Mycophenolate mofetil (MMF)
Oral, capsule
Lék: 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
Lék: Cyclosporine
Oral, capsule
Ostatní jména:
  • The cyclosporine used in this study will be in the modified formulation with enhanced bioavailability.

Co je měření studie?

Primární výstupní opatření

Měření výsledku
Popis opatření
Časové okno
Number of Participants With an Episode of Clinically-suspected and Biopsy-proven Acute Rejection (CSPAR)
Časové okno: 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)

Sekundární výstupní opatření

Měření výsledku
Popis opatření
Časové okno
Percentage of Participants With Biopsy-proven Acute Rejection (BPAR) Through Months 6 and 12
Časové okno: 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
Časové okno: 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)
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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 )

Další výstupní opatření

Měření výsledku
Popis opatření
Časové okno
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
Časové okno: 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
Časové okno: 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)

Spolupracovníci a vyšetřovatelé

Zde najdete lidi a organizace zapojené do této studie.

Sponzor

Bristol-Myers Squibb

Termíny studijních záznamů

Tato data sledují průběh záznamů studie a předkládání souhrnných výsledků na ClinicalTrials.gov. Záznamy ze studií a hlášené výsledky jsou před zveřejněním na veřejné webové stránce přezkoumány Národní lékařskou knihovnou (NLM), aby se ujistily, že splňují specifické standardy kontroly kvality.

Hlavní termíny studia

Začátek studia

1. března 2001

Primární dokončení (Aktuální)

1. ledna 2004

Dokončení studie (Aktuální)

1. července 2012

Termíny zápisu do studia

První předloženo

3. května 2002

První předloženo, které splnilo kritéria kontroly kvality

3. května 2002

První zveřejněno (Odhad)

6. května 2002

Aktualizace studijních záznamů

Poslední zveřejněná aktualizace (Odhad)

13. ledna 2014

Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality

27. listopadu 2013

Naposledy ověřeno

1. listopadu 2013

Více informací

Termíny související s touto studií

Klíčová slova

Další relevantní podmínky MeSH

Další identifikační čísla studie

  • IM103-100

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