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A Phase II Study of Belatacept (BMS-224818) With a Steroid-free Regimen in Subjects Undergoing Kidney Transplantation

27 maja 2014 zaktualizowane przez: Bristol-Myers Squibb

A Randomized, Open-Label, Multicenter, Parallel-Group Study of Belatacept (BMS-224818)-Based Corticosteroid-Free Regimens in Renal Transplant

The purpose of this clinical research study is to learn if belatacept (BMS-224818) is expected to show acceptable rates of acute rejection (AR) in steroid-free belatacept-based immunosuppressive regiments compared to a similar steroid-free tacrolimus regimen. The long-term safety and tolerability of belatacept based regimens following long-term administration in subjects who have received a kidney transplant

Przegląd badań

Status

Zakończony

Warunki

Interwencja / Leczenie

Typ studiów

Interwencyjne

Zapisy (Rzeczywisty)

93

Faza

  • Faza 2

Kontakty i lokalizacje

Ta sekcja zawiera dane kontaktowe osób prowadzących badanie oraz informacje o tym, gdzie badanie jest przeprowadzane.

Lokalizacje studiów

  • Hiszpania
      • Barcelona, Hiszpania, 08907
        • Local Institution
      • Sevilla, Hiszpania, 41013
        • Local Institution
  • Stany Zjednoczone
    • California
      • San Francisco, California, Stany Zjednoczone, 94143
        • UCSF
    • Colorado
      • Denver, Colorado, Stany Zjednoczone, 80262
        • University of Colorado Health Sciences Center
      • Denver, Colorado, Stany Zjednoczone, 80218
        • Denver Nephrology, Pc
    • Georgia
      • Augusta, Georgia, Stany Zjednoczone, 30912
        • Medical College of Georgia
    • Illinois
      • Chicago, Illinois, Stany Zjednoczone, 60611
        • Northwestern University Feinberg School of Medicine
    • Michigan
      • Detriot, Michigan, Stany Zjednoczone, 48202
        • Henry Ford Hospital
    • New York
      • Albany, New York, Stany Zjednoczone, 12208
        • Albany Medical College
    • North Carolina
      • Charlotte, North Carolina, Stany Zjednoczone, 28203
        • Carolinas Medical Center
    • Ohio
      • Cincinnati, Ohio, Stany Zjednoczone, 45267
        • University of Cincinnati
      • Columbus, Ohio, Stany Zjednoczone, 43210
        • Ohio State University Medical Center
    • Tennessee
      • Nashville, Tennessee, Stany Zjednoczone, 37232
        • Vanderbilt University Medical Center
  • Włochy
      • Bologna, Włochy, 40138
        • Local Institution
      • Brescia, Włochy, 25123
        • Local Institution
      • Padova, Włochy, 35128
        • Local Institution
      • Roma, Włochy, 00168
        • Local Institution

Kryteria uczestnictwa

Badacze szukają osób, które pasują do określonego opisu, zwanego kryteriami kwalifikacyjnymi. Niektóre przykłady tych kryteriów to ogólny stan zdrowia danej osoby lub wcześniejsze leczenie.

Kryteria kwalifikacji

Wiek uprawniający do nauki

18 lat do 70 lat (Dorosły, Starszy dorosły)

Akceptuje zdrowych ochotników

Nie

Płeć kwalifikująca się do nauki

Wszystko

Opis

Inclusion Criteria:

  • Living or deceased donor renal allograft
  • Men and women, 18 to 70 years old
  • Subjects who have received a de novo kidney transplant, who have completed the initial study treatment through Month 12, and are willing to sign informed consent will be eligible to continue into the long term extension phase

Exclusion Criteria:

  • Pregnant or breastfeeding women
  • Epstein Barr Virus (EBV) negative serology
  • First time renal transplant with panel reactive antibody (PRA) ≥ 50% or retransplantation with PRA > 30%
  • Graft loss due to AR
  • Positive T-cell or B-cell crossmatch
  • Recipients/donors with HIV or hepatitis B/C
  • Active tuberculosis (TB)
  • Immunosuppressive therapy within 1 year of enrollment
  • UNOS ECD organs will be excluded
  • Body mass index (BMI) > 35 kg/m²
  • Subjects who have developed any malignancy (other than non-melanoma skin cancer) or other medical condition that, in the investigator's opinion, should not be treated with an experimental immunosuppressive drug like belatacept

Plan studiów

Ta sekcja zawiera szczegółowe informacje na temat planu badania, w tym sposób zaprojektowania badania i jego pomiary.

Jak projektuje się badanie?

Szczegóły projektu

  • Główny cel: Leczenie
  • Przydział: Randomizowane
  • Model interwencyjny: Przydział równoległy
  • Maskowanie: Brak (otwarta etykieta)

Broń i interwencje

Grupa uczestników / Arm
Interwencja / Leczenie
Eksperymentalny: belatacept, mycophenolate mofetil (MMF)
thymoglobulin 1.5mg/kg for 4 days;IV belatacept: 10 mg/kg Days 1 and 5, then every other week through Month 3 (Weeks 2,4,6,8,10,12), and then every 4 weeks through Month 6 (Weeks 16, 20, 24),after 6 months, 5 mg/kg every 4 weeks until 12 months; MMF 1g twice daily(bis in die, BID)
Lek: Thymoglobulin
Induction therapy, IV infusion, All subjects will receive thymoglobulin 1.5-mg/kg i.v. infusion on Days 1 (day of transplant), 2, 3, and 4 (up to a maximum total dose of 6 mg/kg) i.v. infusion over at least 4 hours
Lek: Belatacept
Belatacept arms will receive i.v. belatacept (10 mg/kg) on Days 1 and 5, and then every other week through Month 3 (Weeks 2, 4, 6, 8, 10, and 12), and then every 4 weeks through Month 6 (Weeks 16, 20, and 24). After 6 months, subjects will receive belatacept at the maintenance dose of 5 mg/kg every 4 weeks until completion of the trial
Inne nazwy:
  • BMS-224818
Lek: Mycophenolate Mofetil (MMF)
Administered orally in a capsule or solution formulation in 2 divided doses on a consistent schedule in relation to time of day and meals. The dose should be 1 g bid; however 1.5 g bid may be administered at the investigator's discretion until completion of the trial
Eksperymentalny: belatacept, sirolimus
thymoglobulin 1.5mg/kg for 4 days;IV belatacept: 10 mg/kg Days 1 and 5, then every other week through Month 3 (Weeks 2,4,6,8,10,12), and then every 4 weeks through Month 6 (Weeks 16, 20, 24),after 6 months, 5 mg/kg every 4 weeks until 12 months;sirolimus 5 mg/day on Day 1 (day of transplant)and continued through Day 2, dosing to be adjusted to keep pre-dose C0 levels at 7-12 ng/mL for first 6 months, followed by 5 - 10 ng/mL until 12 months.
Lek: Thymoglobulin
Induction therapy, IV infusion, All subjects will receive thymoglobulin 1.5-mg/kg i.v. infusion on Days 1 (day of transplant), 2, 3, and 4 (up to a maximum total dose of 6 mg/kg) i.v. infusion over at least 4 hours
Lek: Belatacept
Belatacept arms will receive i.v. belatacept (10 mg/kg) on Days 1 and 5, and then every other week through Month 3 (Weeks 2, 4, 6, 8, 10, and 12), and then every 4 weeks through Month 6 (Weeks 16, 20, and 24). After 6 months, subjects will receive belatacept at the maintenance dose of 5 mg/kg every 4 weeks until completion of the trial
Inne nazwy:
  • BMS-224818
Lek: Sirolimus
Sirolimus will be initiated at 5 mg/day on Day 1 (day of transplant) and continued through Day 2. The dosing will be adjusted subsequently to keep pre-dose (C0) levels at 7 - 12 ng/mL for the first 6 months, followed by 5 - 10 ng/mL thereafter
Inny: tacrolimus, MMF
(IMPs as comparator regimen)thymoglobulin 1.5mg/kg for 4 days; oral tacrolimus 0.1 mg/kg/day in 2 divided doses with initial targeted trough level of 8-12 ng/mL for Days 1 - 30 with dose reduction to achieve 12 hour trough target of 5-10 ng/mL for 12 months; MMF (mycophenolate mofetil) 1g BID.
Lek: Thymoglobulin
Induction therapy, IV infusion, All subjects will receive thymoglobulin 1.5-mg/kg i.v. infusion on Days 1 (day of transplant), 2, 3, and 4 (up to a maximum total dose of 6 mg/kg) i.v. infusion over at least 4 hours
Lek: Mycophenolate Mofetil (MMF)
Administered orally in a capsule or solution formulation in 2 divided doses on a consistent schedule in relation to time of day and meals. The dose should be 1 g bid; however 1.5 g bid may be administered at the investigator's discretion until completion of the trial
Lek: Tacrolimus
The recommended total initial dose of tacrolimus is 0.1 mg/kg/day in two divided doses orally up to and including week 52. Post week 52 subjects assigned to the tacrolimus arm will receive tacrolimus orally in accordance with local practice and the package insert until completion of the trial

Co mierzy badanie?

Podstawowe miary wyniku

Miara wyniku
Opis środka
Ramy czasowe
Number of Participants With Acute Rejection (AR) of Transplant up to 6 Months Post Transplantation - Intent to Treat (ITT) Population
Ramy czasowe: Day 1 to Month 6 post-transplantation
AR is clinicopathological event requiring clinical evidence and biopsy confirmation by central pathologist. One or more conditions were met and a renal biopsy revealed histologic evidence of rejection: unexplained rise of serum creatine (SCr) greater than or equal to 25% from baseline plus one or more of the following: unexplained decreased urine output; fever, graft tenderness; SCr that remained elevated 14 days post-transplantation and clinical suspicion of AR; other reason and participant treated for episode. Day 1=transplantation. Banff 97 working classification of kidney transplant pathology: Type I=tubulointerstitial AR without arteritis (IA: interstitial infiltration with >25% of parenchyma affected and moderate tubulitis with >4 mononuclear cells/tubular cross section; IB: >10 mononuclear cells; Type II vascular AR with (IA) intimal arteritis (IIA=mild - moderate; IIB=severe; Type III=severe rejection with transmural arterial changes, necrosis of smooth muscle cells.
Day 1 to Month 6 post-transplantation

Miary wyników drugorzędnych

Miara wyniku
Opis środka
Ramy czasowe
Number of Participants With Acute Rejection of Transplant up to Month 12 Post Transplantation - Intent to Treat Population
Ramy czasowe: Day 1 to Month 12 post transplantation
AR defined as a clinicopathological event requiring clinical evidence and biopsy confirmation by central pathologist. One or more conditions were met and a renal biopsy revealed histologic evidence of rejection: unexplained rise of serum creatine (SCr) >= 25 % from baseline plus one or more of the following: unexplained decreased urine output; fever and graft tenderness; a SCr that remained elevated within 14 days after transplantation and clinical suspicion of AR; reason other than those listed and participant was treated for this episode. Day 1 was day of transplantation. Banff grade used Banff 97 working classification of kidney transplant pathology. ITT population was all randomized and transplanted participants.
Day 1 to Month 12 post transplantation
Number of Participants With Graft Loss or Death up to Month 6 and Month 12 Post Transplantation - Intent to Treat Population
Ramy czasowe: Day 1 to Month 6 and Month 12 post transplantation
Graft loss was defined as either functional loss or physical loss. Functional loss was defined as either: sustained level of SCr greater than or equal to (>=) 6.0 mg/dL (530 micromoles/Liter; micromol/L) for >= 4 weeks as determined by the local laboratory; regularly scheduled dialysis treatments over a period of 56 days; impairment of renal function to such a degree that the participant undergoes re-transplant. Day 1 was day of transplantation. ITT population defined as all participants randomized and transplanted.
Day 1 to Month 6 and Month 12 post transplantation
Number of Participants With Composite of Death, Graft Loss and Acute Rejection up to Month 6 - Intent to Treat Population
Ramy czasowe: Day 1 up to Month 6
Participants with graft loss or death prior to Month 6 were considered having an event of AR, therefore, the incidence of AR was reported as a composite of AR, death, and graft loss.
Day 1 up to Month 6
Number of Participants With Composite of Death, Graft Loss and Acute Rejection up to Month 12 - Intent to Treat Population
Ramy czasowe: Day 1 up to Month 12
Subjects with graft loss or death prior to Month 12 were considered having an event of AR, therefore, the incidence of AR was reported as a composite of AR, death, and graft loss.
Day 1 up to Month 12
Number of Participants With Delayed Graft Function - Intent to Treat Population
Ramy czasowe: From Day 1 up to and including Day 8 post transplantation
Delayed graft function (DGF) is defined as participant requiring dialysis within the first week (Day 1-8) post transplantation. Participants losing their graft less than 48 hours post transplant and receiving chronic dialysis were not considered as having DGF. Day 1 was day of transplantation. Intent to treat population defined as all participants randomized and transplanted
From Day 1 up to and including Day 8 post transplantation
Number of Participants With New Onset Diabetes Mellitus From Baseline to Month 12 Post Transplantation - Intent to Treat Population
Ramy czasowe: Baseline to Month 12

Baseline defined as day before transplantation. A participant who did not have diabetes prior to randomization and received an antidiabetic medication for a duration of at least 30 days or a participant who meets the following criteria and did not have diabetes prior to randomization: Symptoms of diabetes plus casual plasma glucose (PG) concentration ≥ 200 mg/dL (11.1 mmol/L); or fasting plasma glucose ≥ 126 mg/dL (7.0 mmol/L); or 2-hour PG ≥ 200 mg/dL (11.1 mmol/L) during an oral glucose tolerance test and a confirmatory laboratory test based on measurements of venous PG must have been done on another day in the absence of unequivocal hyperglycemia accompanied by acute metabolic decompensation.

Intent to treat population included all participants randomized and transplanted.
Baseline to Month 12
Number of Participants Who Used Anti-hypertension Medications at Baseline and at 12 Months Post Transplantation - Intent to Treat Population
Ramy czasowe: Baseline and Month 12
Baseline was defined as day prior to transplantation. Number of anti-hypertension medications taken were categorized from 1 to 6 and greater than (>)6. Intent to treat population included all participants randomized and transplanted.
Baseline and Month 12
Mean Systolic, Diastolic and Arterial Blood Pressure at Baseline and Month 12 - Intent to Treat Population
Ramy czasowe: Baseline and 12 months post transplantation
Systolic, diastolic and mean arterial blood pressures were measured in millimeters of mercury (mm Hg). Baseline was defined as value obtained before transplantation. Intent to treat population included all participants randomized and transplanted.
Baseline and 12 months post transplantation
Number of Participants Using Antihyperlipidemic Medications at Month 12 - Intent to Treat Population
Ramy czasowe: Month 12
Participants using > = 1 antihyperlipidemic medication at Month 12.
Month 12
Mean Change From Baseline (BL) to Month 12 Post Transplantation in Lipid Values - Intent to Treat Population
Ramy czasowe: Baseline to Month 12
Baseline (BL) was value obtained day prior to transplantation. Lipid values measured in milligrams/deciliter (mg/dL) included: high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), non-HDL cholesterol (non-HDL-C), total cholesterol (TC), triglycerides. Intent to treat population included all participants randomized and transplanted.
Baseline to Month 12
Mean (Standard Deviation) in Calculated Glomerular Filtration Rate (GFR) mL/Min/1.73m^2 at Month 3, Month 6 and Month 12 Post Transplantation - Intent to Treat Population
Ramy czasowe: Months 3, 6 and 12 post transplantation
Blood urea nitrogen (BUN) in mg/dL; Albumin (Alb) in g/dL;Serum creatinine (SCr) in mg/dL; Age in years. Glomerular filtration rate (GFR) was calculated based upon serum creatinine (SCr) using the Modification of Diet in Renal Disease (MDRD) formula as suggested by Levey et al: MDRD GFR = 170 x [SCr/0.95]^(-0.999) x [Age]^(-0.176) x [0.762 if participant was female] x [1.180 if participant was black] x [BUN]^(-0.170) x [Alb]^(+0.318). Intent to Treat (ITT) population is defined as all participants randomized and transplanted.
Months 3, 6 and 12 post transplantation
Number of Corticosteroid-free Participants at 6 and 12 Months Post Transplantation - Intent to Treat Population
Ramy czasowe: Day 1 through Month 12
Participants were said to be corticosteroid-free at Month 6 if they were not receiving corticosteroids for greater than (>) 7 consecutive days during Days 141 through Days 196, and at Month 12 if not receiving corticosteroids for > 7 days during Days 337 through 392. Intent to treat population included all randomized and transplanted participants.
Day 1 through Month 12
Number of Participants Who Were Corticosteroid-free at Months 6 and 12 and Number of Participants Who Were Both Calcineurin Inhibitor-free (CNI-free)and Corticosteroid-free at Months 6 and 12 Post Transplantation - Intent to Treat Population
Ramy czasowe: Day 1 to Month 12 post transplantation
Participants were said to be CNI-free at Month 6 or 12 if they were not receiving a CNI during Day 141 to Day 196, or Day 337 to Day 392. Participants in the tacrolimus arm were not relevant to this analysis because tacrolimus is a calcinurin inhibitor. Participants were corticosteroid-free (CS-free) at Month 6 if they were not receiving corticosteroids for > 7 consecutive days during Days 141 through Days 196, and at Month 12 if not receiving corticosteroids for > 7 days during Days 337 through 392. Day 1 was day of transplantation. Intent to treat population included all randomized and transplanted participants.
Day 1 to Month 12 post transplantation
Number of Participants With Acute Rejection of Transplant up to End of Month 48 Post Transplantation - Intent to Treat Population in Long Term Extension
Ramy czasowe: End of Month 12 to end of Month 48 Post Transplantation
AR defined as a clinicopathological event requiring clinical evidence and biopsy confirmation by central pathologist. One or more conditions were met and a renal biopsy revealed histologic evidence of rejection: unexplained rise of serum creatine (SCr) >= 25 % from baseline plus one or more of the following: unexplained decreased urine output; fever and graft tenderness; a SCr that remained elevated within 14 days after transplantation and clinical suspicion of AR; reason other than those listed and participant was treated for this episode. Day 1 was day of transplantation. Banff grade used Banff 97 working classification of kidney transplant pathology. ITT population was all randomized and transplanted participants.
End of Month 12 to end of Month 48 Post Transplantation
Number of Participants With Graft Loss or Death at Months 24, 36, 48 Post Transplantation - Intent to Treat Population in Long Term Extension
Ramy czasowe: End of Month 12 to end of Long Term Extension (Year 4)
Graft loss was defined as either functional loss or physical loss. Functional loss was defined as either: sustained level of SCr greater than or equal to (>=) 6.0 mg/dL (530 micromoles/Liter; micromol/L) for >= 4 weeks as determined by the local laboratory; regularly scheduled dialysis treatments over a period of 56 days; impairment of renal function to such a degree that the participant undergoes re-transplant. Day 1 was day of transplantation. ITT population defined as all participants randomized and transplanted.
End of Month 12 to end of Long Term Extension (Year 4)
Mean (Standard Deviation) in Calculated Glomerular Filtration Rate (GFR) mL/Min/1.73m^2 at Months 24, 36 and 48 Post Transplantation - Intent to Treat Population in Long Term Extension
Ramy czasowe: Months 24, 36 and 48 post transplantation
GFR was calculated based upon serum creatinine (SCr) using the Modification of Diet in Renal Disease (MDRD) formula as suggested by Levey et al: MDRD GFR = 170 x [SCr/0.95]^(-0.999) x [Age]^(-0.176) x [0.762 if participant was female] x [1.180 if participant was black] x [BUN]^(-0.170) x [Alb]^(+0.318). Age in years, Alb = Albumin in g/dL; SCr = in mg/dL; BUN =Blood urea nitrogen in mg/dL. Intent to Treat population is defined as all participants randomized and transplanted.
Months 24, 36 and 48 post transplantation
Number of Corticosteroid-free Participants at Months 24, 36, 48 Post Transplantation - Intent to Treat Population in Long Term Extension
Ramy czasowe: End of Month 12 to end of Long Term Extension (Year 4)
In the LTE, a participant was considered corticosteroid-free if they were not receiving corticosteroids for >7 consecutive days during Day 701 and Day 756, Day 1065 and Day 1120, as well as Day 1429 and Day 1484, respectively.
End of Month 12 to end of Long Term Extension (Year 4)
Number of Participants Who Were Both Calcineurin Inhibitor-free (CNI-free)and Corticosteroid-free at Months 24, 36, 48 Post Transplantation - Intent to Treat Population in Long Term Extension
Ramy czasowe: Months 24, 36, 48
Participants were considered corticosteroid-free at Months 24, 36, and 48 if they were not receiving corticosteroids for >7 consecutive days during Day 701 and Day 756, Day 1065 and Day 1120, as well as Day 1429 and Day 1484, respectively. Participants were considered CNI-free at Months 24, 36, and 48 if they were not receiving CNI during Day 701 and Day 756, Day 1065 and Day 1120, as well as Day 1429 and Day 1484, respectively. Participants in the tacrolimus arm were not relevant to this analysis because tacrolimus is a calcinurin inhibitor.
Months 24, 36, 48
Number of Participants Who Switched Between MMF and Sirolimus During Long Term Extension up to Study Completion
Ramy czasowe: End of Month 12 to end of Study (Month 48)
Long Term extension was the period from the end of Month 12 to the end of Month 48 post transplantation and the completion of the study 31 July 2012. At any time in the study, participants who were unable to tolerate MMF in the Bela-MMF and Tac-MMF groups could discontinue (DC) MMF and switch to sirolimus and remain in the study and those in the Bela-Siro group who were unable to tolerate sirolimus could DC sirolimus and switch to MMF and remain in the study. Study completion=data base (DB) lock.
End of Month 12 to end of Study (Month 48)

Współpracownicy i badacze

Tutaj znajdziesz osoby i organizacje zaangażowane w to badanie.

Sponsor

Bristol-Myers Squibb

Daty zapisu na studia

Daty te śledzą postęp w przesyłaniu rekordów badań i podsumowań wyników do ClinicalTrials.gov. Zapisy badań i zgłoszone wyniki są przeglądane przez National Library of Medicine (NLM), aby upewnić się, że spełniają określone standardy kontroli jakości, zanim zostaną opublikowane na publicznej stronie internetowej.

Główne daty studiów

Rozpoczęcie studiów

1 lipca 2007

Zakończenie podstawowe (Rzeczywisty)

1 października 2008

Ukończenie studiów (Rzeczywisty)

1 sierpnia 2012

Daty rejestracji na studia

Pierwszy przesłany

30 marca 2007

Pierwszy przesłany, który spełnia kryteria kontroli jakości

30 marca 2007

Pierwszy wysłany (Oszacować)

2 kwietnia 2007

Aktualizacje rekordów badań

Ostatnia wysłana aktualizacja (Oszacować)

9 czerwca 2014

Ostatnia przesłana aktualizacja, która spełniała kryteria kontroli jakości

27 maja 2014

Ostatnia weryfikacja

1 maja 2014

Więcej informacji

Terminy związane z tym badaniem

Słowa kluczowe

Dodatkowe istotne warunki MeSH

Inne numery identyfikacyjne badania

  • IM103-034

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