Study Comparing the Safety and Efficacy of Belatacept With That of Cyclosporine in Patients With a Transplanted Kidney
27. November 2013 aktualisiert von: 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).
Studienübersicht
Status
Abgeschlossen
Studientyp
Interventionell
Einschreibung (Tatsächlich)
230
Phase
- Phase 2
Kontakte und Standorte
Dieser Abschnitt enthält die Kontaktdaten derjenigen, die die Studie durchführen, und Informationen darüber, wo diese Studie durchgeführt wird.
Studienorte
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California
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San Francisco, California, Vereinigte Staaten, 94143-0001
- Univ. of Calif. - San Francisco
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Georgia
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Atlanta, Georgia, Vereinigte Staaten, 30322
- Emory Univ. School of Medicine
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Maryland
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Baltimore, Maryland, Vereinigte Staaten, 21205
- Johns Hopkins University
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Massachusetts
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Boston, Massachusetts, Vereinigte Staaten, 02114
- Massachusetts General Hospital
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Minnesota
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Rochester, Minnesota, Vereinigte Staaten, 55905
- Mayo Clinic
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Nebraska
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Omaha, Nebraska, Vereinigte Staaten, 68198-1002
- Univ. of Nebraska Medical Center
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New Jersey
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Livingston, New Jersey, Vereinigte Staaten, 07039
- Saint Barnabas Medical Center
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New York
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New York, New York, Vereinigte Staaten, 10029-6574
- Mount Sinai Medical Center
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Pennsylvania
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Philadelphia, Pennsylvania, Vereinigte Staaten, 19104
- Univ. of Pennsylvania
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South Carolina
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Charleston, South Carolina, Vereinigte Staaten, 29425
- Medical Univ. of South Carolina
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Texas
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Dallas, Texas, Vereinigte Staaten, 75246
- Baylor Univ. Medical Center
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Wisconsin
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Madison, Wisconsin, Vereinigte Staaten, 53792-7375
- Univ. of Wisconsin
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Teilnahmekriterien
Forscher suchen nach Personen, die einer bestimmten Beschreibung entsprechen, die als Auswahlkriterien bezeichnet werden. Einige Beispiele für diese Kriterien sind der allgemeine Gesundheitszustand einer Person oder frühere Behandlungen.
Zulassungskriterien
Studienberechtigtes Alter
18 Jahre und älter (Erwachsene, Älterer Erwachsener)
Akzeptiert gesunde Freiwillige
Nein
Studienberechtigte Geschlechter
Alle
Beschreibung
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.
Studienplan
Dieser Abschnitt enthält Einzelheiten zum Studienplan, einschließlich des Studiendesigns und der Messung der Studieninhalte.
Wie ist die Studie aufgebaut?
Designdetails
- Hauptzweck: Verhütung
- Zuteilung: Zufällig
- Interventionsmodell: Parallele Zuordnung
- Maskierung: Keine (Offenes Etikett)
Waffen und Interventionen
Teilnehmergruppe / Arm |
Intervention / Behandlung |
|---|---|
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Experimental: 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.
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Solution, intravenous
Andere Namen:
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
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Experimental: 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
Andere Namen:
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
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Experimental: 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
Andere Namen:
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Was misst die Studie?
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
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Number of Participants With an Episode of Clinically-suspected and Biopsy-proven Acute Rejection (CSPAR)
Zeitfenster: By Month 6 posttransplant (From Day 1 to Month 6)
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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.
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By Month 6 posttransplant (From Day 1 to Month 6)
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Sekundäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
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Percentage of Participants With Biopsy-proven Acute Rejection (BPAR) Through Months 6 and 12
Zeitfenster: Through Months 6 and 12 posttransplant (From Day 1 to Months 6 and 12)
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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.
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Through Months 6 and 12 posttransplant (From Day 1 to Months 6 and 12)
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Percentage of Participants With Biopsy-proven Acute Rejection (BPAR) or Who Received Treatment for Acute Rejection
Zeitfenster: By Months 3, 6, and 12 posttransplant (Day 1 to Months 3, 6, and 12)
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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).
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By Months 3, 6, and 12 posttransplant (Day 1 to Months 3, 6, and 12)
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Percentage of Participants With Acute Rejection or Presumed Acute Rejection (PAR)
Zeitfenster: By Months 6 and 12 posttransplant (Day 1 to Months 6 and 12)
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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.
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By Months 6 and 12 posttransplant (Day 1 to Months 6 and 12)
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Percentage of Participants Who Had Chronic Allograft Nephropathy
Zeitfenster: By Months 6 and 12 posttransplant (Day 1 to Months 6 and 12)
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Based on postbaseline biopsies
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By Months 6 and 12 posttransplant (Day 1 to Months 6 and 12)
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Mean Iohexol Clearance
Zeitfenster: By Months 1, 6, and 12 posttransplant (Day 1 to Months 1, 6, and 12)
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Iohexol, a true glomerular filtration marker, is used to measure glomerular filtration rate.
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By Months 1, 6, and 12 posttransplant (Day 1 to Months 1, 6, and 12)
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Percentage of Participants Who Used Antihypertensive Medication
Zeitfenster: By Months 6 and 12 posttransplant (Day 1 to Months 6 and 12)
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Hypertension is defined as diastolic blood pressure ≥90 mm Hg and/or systolic blood pressure ≥140 mm Hg
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By Months 6 and 12 posttransplant (Day 1 to Months 6 and 12)
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Number of Participants With Hypertension
Zeitfenster: By Months 6 and 12 posttransplant (Day 1 to Months 6 and 12)
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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.
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By Months 6 and 12 posttransplant (Day 1 to Months 6 and 12)
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Mean LDL Cholesterol, HDL Cholesterol, Total Cholesterol, Triglyceride, and Non-HDL Levels
Zeitfenster: By Months 1, 6, and 12 posttransplant (Day 1 to Months 1, 6, and 12)
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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.
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By Months 1, 6, and 12 posttransplant (Day 1 to Months 1, 6, and 12)
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Number of Participants With Posttransplant Diabetes Mellitus
Zeitfenster: By Months 1, 3, 6, 9, and 12 posttransplant (Day 1 to Months 1, 3, 6, 9, and 12 )
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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
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By Months 1, 3, 6, 9, and 12 posttransplant (Day 1 to Months 1, 3, 6, 9, and 12 )
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Andere Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
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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
Zeitfenster: 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.
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Day 1 (posttransplant) continuously to 56 days following last dose of study medication
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Number of Participants Meeting Marked Abnormality Criteria for Select Hemolytic, Blood Chemistry, and Urinalysis Laboratory Test Results
Zeitfenster: 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.
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Days 8 and Months 1, 3, 6, 9, and 12 posttransplant (from Day 1)
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Mitarbeiter und Ermittler
Hier finden Sie Personen und Organisationen, die an dieser Studie beteiligt sind.
Sponsor
Studienaufzeichnungsdaten
Diese Daten verfolgen den Fortschritt der Übermittlung von Studienaufzeichnungen und zusammenfassenden Ergebnissen an ClinicalTrials.gov. Studienaufzeichnungen und gemeldete Ergebnisse werden von der National Library of Medicine (NLM) überprüft, um sicherzustellen, dass sie bestimmten Qualitätskontrollstandards entsprechen, bevor sie auf der öffentlichen Website veröffentlicht werden.
Haupttermine studieren
Studienbeginn
1. März 2001
Primärer Abschluss (Tatsächlich)
1. Januar 2004
Studienabschluss (Tatsächlich)
1. Juli 2012
Studienanmeldedaten
Zuerst eingereicht
3. Mai 2002
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
3. Mai 2002
Zuerst gepostet (Schätzen)
6. Mai 2002
Studienaufzeichnungsaktualisierungen
Letztes Update gepostet (Schätzen)
13. Januar 2014
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
27. November 2013
Zuletzt verifiziert
1. November 2013
Mehr Informationen
Begriffe im Zusammenhang mit dieser Studie
Schlüsselwörter
Zusätzliche relevante MeSH-Bedingungen
- Physiologische Wirkungen von Arzneimitteln
- Molekulare Mechanismen der pharmakologischen Wirkung
- Antiinfektiva
- Enzym-Inhibitoren
- Antirheumatika
- Antineoplastische Mittel
- Immunsuppressive Mittel
- Immunologische Faktoren
- Dermatologische Wirkstoffe
- Antibakterielle Mittel
- Antibiotika, antineoplastische
- Antimykotika
- Immun-Checkpoint-Inhibitoren
- Antituberkulöse Mittel
- Antibiotika, Antituberkulose
- Calcineurin-Inhibitoren
- Mycophenolsäure
- Abatacept
- Cyclosporin
- Cyclosporine
Andere Studien-ID-Nummern
- IM103-100
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