Study Comparing the Safety and Efficacy of Belatacept With That of Cyclosporine in Patients With a Transplanted Kidney
27. november 2013 oppdatert av: 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).
Studieoversikt
Status
Fullført
Intervensjon / Behandling
Studietype
Intervensjonell
Registrering (Faktiske)
230
Fase
- Fase 2
Kontakter og plasseringer
Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.
Studiesteder
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California
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San Francisco, California, Forente stater, 94143-0001
- Univ. of Calif. - San Francisco
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Georgia
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Atlanta, Georgia, Forente stater, 30322
- Emory Univ. School of Medicine
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Maryland
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Baltimore, Maryland, Forente stater, 21205
- Johns Hopkins University
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Massachusetts
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Boston, Massachusetts, Forente stater, 02114
- Massachusetts General Hospital
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Minnesota
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Rochester, Minnesota, Forente stater, 55905
- Mayo Clinic
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Nebraska
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Omaha, Nebraska, Forente stater, 68198-1002
- Univ. of Nebraska Medical Center
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New Jersey
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Livingston, New Jersey, Forente stater, 07039
- Saint Barnabas Medical Center
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New York
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New York, New York, Forente stater, 10029-6574
- Mount Sinai Medical Center
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Pennsylvania
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Philadelphia, Pennsylvania, Forente stater, 19104
- Univ. of Pennsylvania
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South Carolina
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Charleston, South Carolina, Forente stater, 29425
- Medical Univ. of South Carolina
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Texas
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Dallas, Texas, Forente stater, 75246
- Baylor Univ. Medical Center
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Wisconsin
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Madison, Wisconsin, Forente stater, 53792-7375
- Univ. of Wisconsin
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Deltakelseskriterier
Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
18 år og eldre (Voksen, Eldre voksen)
Tar imot friske frivillige
Nei
Kjønn som er kvalifisert for studier
Alle
Beskrivelse
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.
Studieplan
Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Forebygging
- Tildeling: Randomisert
- Intervensjonsmodell: Parallell tildeling
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
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Eksperimentell: 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
Andre navn:
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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Eksperimentell: 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
Andre navn:
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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Eksperimentell: 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
Andre navn:
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Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
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Number of Participants With an Episode of Clinically-suspected and Biopsy-proven Acute Rejection (CSPAR)
Tidsramme: 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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Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
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Percentage of Participants With Biopsy-proven Acute Rejection (BPAR) Through Months 6 and 12
Tidsramme: 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
Tidsramme: 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)
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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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Andre resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
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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
Tidsramme: Day 1 (posttransplant) continuously to 56 days following last dose of study medication
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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
Tidsramme: Days 8 and Months 1, 3, 6, 9, and 12 posttransplant (from Day 1)
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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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Samarbeidspartnere og etterforskere
Det er her du vil finne personer og organisasjoner som er involvert i denne studien.
Sponsor
Studierekorddatoer
Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.
Studer hoveddatoer
Studiestart
1. mars 2001
Primær fullføring (Faktiske)
1. januar 2004
Studiet fullført (Faktiske)
1. juli 2012
Datoer for studieregistrering
Først innsendt
3. mai 2002
Først innsendt som oppfylte QC-kriteriene
3. mai 2002
Først lagt ut (Anslag)
6. mai 2002
Oppdateringer av studieposter
Sist oppdatering lagt ut (Anslag)
13. januar 2014
Siste oppdatering sendt inn som oppfylte QC-kriteriene
27. november 2013
Sist bekreftet
1. november 2013
Mer informasjon
Begreper knyttet til denne studien
Nøkkelord
Ytterligere relevante MeSH-vilkår
- Fysiologiske effekter av legemidler
- Molekylære mekanismer for farmakologisk virkning
- Anti-infeksjonsmidler
- Enzymhemmere
- Antirevmatiske midler
- Antineoplastiske midler
- Immunsuppressive midler
- Immunologiske faktorer
- Dermatologiske midler
- Antibakterielle midler
- Antibiotika, antineoplastisk
- Antifungale midler
- Immune Checkpoint-hemmere
- Antituberkulære midler
- Antibiotika, Antituberkulær
- Calcineurin-hemmere
- Mykofenolsyre
- Abatacept
- Syklosporin
- Syklosporiner
Andre studie-ID-numre
- IM103-100
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