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A Study to Assess the Efficacy and Safety of Alefacept in Kidney Transplant Recipients

5 januari 2016 bijgewerkt door: Astellas Pharma Inc

Efficacy and Safety of Alefacept in Combination With Tacrolimus, Mycophenolate Mofetil and Steroids in de Novo Kidney Transplantation - a Multicenter, Randomized, Double-Blind, Placebo Controlled, Parallel Group Study

The purpose of this study is to determine whether alefacept is effective and well tolerated when used with a combination of tacrolimus, mycophenolate mofetil and steroids versus a combination therapy of placebo, tacrolimus and steroids in the prevention of kidney transplant rejection.

Studie Overzicht

Toestand

Voltooid

Conditie

Interventie / Behandeling

Studietype

Ingrijpend

Inschrijving (Werkelijk)

218

Fase

  • Fase 2

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studie Locaties

  • België
      • Bruxelles, België, 1070
      • Bruxelles, België, 1200
      • Gent, België, 9000
      • Leuven, België, 3000
      • Liege, België, 4000
  • Duitsland
      • Bochum, Duitsland, 44892
      • Regensburg, Duitsland, 93053
  • Frankrijk
      • Creteil, Frankrijk, 94010
      • Le Kremlin Bicetre Cedex, Frankrijk, 94275
      • Montpellier, Frankrijk, 34295
      • Nantes Cedex 1, Frankrijk, 44093
      • Nice Cedex 1, Frankrijk, 6002
      • Paris, Frankrijk, 75475
      • Toulouse Cedex, Frankrijk, 31054
  • Hongarije
      • Budapest, Hongarije, 1082
  • Italië
      • Bologna, Italië, 40138
      • Padova, Italië, 35128
      • Rome, Italië, 00168
      • Siena, Italië, 53100
  • Nederland
      • Maastricht, Nederland, 6229
  • Oostenrijk
      • Vienna, Oostenrijk, 1090
  • Polen
      • Bydgoszcz, Polen, 85-094
      • Poznan, Polen, 60-479
      • Szczecin, Polen, 70-111
  • Spanje
      • Barcelona, Spanje, 8036
      • Llobregat, Spanje, 8907
      • Madrid, Spanje, 28041
      • Malaga, Spanje, 29010
      • Santander, Spanje, 39008
  • Tsjechische Republiek
      • Praha, Tsjechische Republiek, 140 21
  • Verenigd Koninkrijk
      • Manchester, Verenigd Koninkrijk, M13 9WL
  • Zweden
      • Goteborg, Zweden, 41345
      • Uppsala, Zweden, 75185

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

18 jaar tot 64 jaar (Volwassen)

Accepteert gezonde vrijwilligers

Nee

Geslachten die in aanmerking komen voor studie

Allemaal

Beschrijving

Inclusion Criteria:

  • Subject with end stage kidney disease who is a suitable candidate for primary kidney transplantation or retransplantation
  • Male or female subject at least 18 years of age and younger than 65 years
  • Subject receiving a kidney transplant from a non-human leucocyte antigen (HLA) identical living donor or deceased HLA identical/non-HLA identical donor between 5 and 59 years of age with compatible ABO blood type (Blood group system A, B, AB and 0)

Exclusion Criteria:

  • Subject has a panel reactivity antibody grade > 20% in the previous 6 months and/or had had a previous graft survival shorter than 1 year due to immunological reasons
  • Subject received a kidney transplant from a non-heart beating donor
  • Subject has received a kidney transplant from a 50 - 59 year old donor with two of the following three factors: history of hypertension, cerebrovascular accident as cause of death, final pre-procurement serum creatinine > 1.5 mg/dL (united network for organ sharing [UNOS] expanded criteria donor)
  • Cold ischemia time of the donor kidney is ≥ 30 hours

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Preventie
  • Toewijzing: Gerandomiseerd
  • Interventioneel model: Parallelle opdracht
  • Masker: Verviervoudigen

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Placebo-vergelijker: Placebo
Participants received placebo administered intra-operatively as an intravenous (IV) bolus on Day 0, another IV bolus on Day 3 and weekly subcutaneous injections thereafter for 12 weeks. Participants also received tacrolimus, mycophenolate mofetil (MMF) and steroid treatment.
Geneesmiddel: placebo
IV and subcutaneous injection
Geneesmiddel: Tacrolimus
The initial daily dose was 0.2 mg/kg orally given in 2 doses commencing 24 hours after completion of surgery.
Geneesmiddel: Mycophenolate Mofetil
Mycophenolic mofetil was administered as 750 mg twice per day orally
Geneesmiddel: Steroids

Methylprednisolone or equivalent:

Day 0: 500 - 1000 mg IV bolus Day 1: 125 - 250 mg IV bolus

Prednisone or equivalent:

Days 2 - 14: 20 - 30 mg orally Days 15 - 28: 10 - 20 mg orally Days 29 - 60: 10 - 15 mg orally Days 61 onwards: 5 - 10 mg orally
Experimenteel: Alefacept
Participants received 7.5 mg alefacept administered intra-operatively as an IV bolus on Day 0, another 7.5 mg IV bolus on Day 3, and weekly subcutaneous injections of 15 mg alefacept thereafter for 12 weeks. Participants also received tacrolimus, MMF and steroid treatment.
Geneesmiddel: Tacrolimus
The initial daily dose was 0.2 mg/kg orally given in 2 doses commencing 24 hours after completion of surgery.
Geneesmiddel: Mycophenolate Mofetil
Mycophenolic mofetil was administered as 750 mg twice per day orally
Geneesmiddel: Steroids

Methylprednisolone or equivalent:

Day 0: 500 - 1000 mg IV bolus Day 1: 125 - 250 mg IV bolus

Prednisone or equivalent:

Days 2 - 14: 20 - 30 mg orally Days 15 - 28: 10 - 20 mg orally Days 29 - 60: 10 - 15 mg orally Days 61 onwards: 5 - 10 mg orally

Geneesmiddel: Alefacept
IV and subcutaneous injection
Andere namen:
  • Tot leven komen

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Percentage of Participants With Biopsy-confirmed Acute T-cell Mediated Rejection at Month 6 Assessed by Local Review
Tijdsspanne: 6 months

Biopsies were graded by the clinical site pathologist.according to the Banff 97/05 updated histological classification:

  • Grade IA: significant interstitial infiltration (>25% parenchyma affected) and foci of moderate tubulitis;
  • Grade IB: significant interstitial infiltration (>25% parenchyma affected) and foci of severe tubulitis;
  • Grade IIA: mild to moderate intimal arteritis;
  • Grade IIB: severe intimal arteritis comprising >25% of the luminal area;
  • Grade III: "transmural" arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells with accompanying lymphocyte inflammation.

A biopsy confirmed acute rejection was an event of suspected acute rejection confirmed by a graft biopsy result of Banff grade ≥ 1.

The Kaplan-Meier estimate of biopsy-confirmed acute T-cell mediated rejection within the first 6 months following transplantation is reported. Participants lost to follow-up or with missing outcomes were censored at their last follow up visit.
6 months

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Percentage of Participants With Biopsy Confirmed Antibody-Mediated Acute Rejection at Month 6
Tijdsspanne: 6 months

Biopsies were graded by the clinical site pathologist.according to the Banff 97/05 updated histological classification:

Acute antibody-mediated rejection - documented anti-donor antibody ('suspicious for' if antibody not demonstrated):

  • Grade I: acute tubular necrosis-like - complement split product positive (C4d+), minimal inflammation;
  • Grade II: capillary-margination and/or thromboses, C4d+
  • Grade III: arterial - v3, C4d+.

A biopsy confirmed acute rejection was an event of suspected acute rejection confirmed by a graft biopsy result of Banff grade ≥ 1.

The Kaplan-Meier estimate of biopsy-confirmed antibody-mediated acute rejection within the first 6 months following transplantation is reported. Participants lost to follow-up or with missing outcomes were censored at their last follow up visit.
6 months
Percentage of Participants With Biopsy Confirmed Acute Rejection (T-Cell Mediated or Antibody Mediated) at Month 6
Tijdsspanne: 6 months

Biopsies were graded by the clinical site pathologist.according to the Banff 97/05 updated histological classification. A biopsy confirmed acute rejection was an event of suspected acute rejection confirmed by a graft biopsy result of Banff grade ≥ 1.

The Kaplan-Meier estimate of biopsy-confirmed acute T-cell mediated or antibody-mediated rejection within the first 6 months following transplantation is reported. Participants lost to follow-up or with missing outcomes were censored at their last follow up visit.
6 months
Percentage of Participants With Biopsy Confirmed Acute Mixed T-Cell Mediated and Antibody-Mediated Rejection at Month 6
Tijdsspanne: 6 months

Biopsies were graded by the clinical site pathologist.according to the Banff 97/05 updated histological classification. A biopsy confirmed acute rejection was an event of suspected acute rejection confirmed by a graft biopsy result of Banff grade ≥ 1.

The Kaplan-Meier estimate of biopsy-confirmed acute mixed T-cell mediated and antibody-mediated rejections within the first 6 months following transplantation is reported. Participants lost to follow-up or with missing outcomes were censored at their last follow up visit.
6 months
Percentage of Participants With Acute Rejection Diagnosed by Signs and Symptoms at Month 6
Tijdsspanne: 6 months
Acute rejection diagnosed by signs and symptoms, including biopsy-confirmed or suspected (not confirmed by biopsy - i.e. no biopsy was performed or biopsy did not confirm an acute T-cell mediated rejection). The Kaplan-Meier estimate of acute rejection diagnosed by signs and symptoms within the first 6 months following transplantation is reported. Participants lost to follow-up or with missing outcomes were censored at their last follow up visit.
6 months
Percentage of Participants With Clinically Treated Acute Rejection at Month 6
Tijdsspanne: 6 months
Patients who received immunosuppressive medications for the treatment of suspected or biopsy-confirmed acute rejections were considered to have a clinically-treated acute rejection. The Kaplan-Meier estimate of clinically treated acute rejection within the first 6 months following transplantation is reported. Participants lost to follow-up or with missing outcomes were censored at their last follow-up visit.
6 months
Percentage of Participants With Steroid-resistant Acute Rejection at Month 6
Tijdsspanne: 6 months

A steroid-resistant acute rejection is defined as a rejection episode which did not resolve following treatment with corticosteroids. In the case that a rejection episode was not treated with corticosteroids first but only with antibodies, it was included in this category.

The Kaplan-Meier estimate of steroid-resistant acute rejection within the first 6 months following transplantation is reported. Participants lost to follow-up or with missing outcomes were censored at their last follow up visit.
6 months
Percentage of Participants With Biopsy-Confirmed Acute T-cell Mediated Rejection as Assessed by Central Review at Month 6
Tijdsspanne: 6 months

Biopsies were graded by the central reviewer according to the Banff 97/05 updated histological classification. A biopsy confirmed acute rejection was an event of suspected acute rejection confirmed by a graft biopsy result of Banff grade ≥ 1.

The Kaplan-Meier estimate of biopsy-confirmed acute T-cell mediated rejection within the first 6 months following transplantation is reported. Participants lost to follow-up or with missing outcomes were censored at their last follow up visit.
6 months
Patient Survival
Tijdsspanne: 6 months
Patient survival is any participant known to be alive at Month 6. The Kaplan-Meier estimate of patient survival within the first 6 months following transplantation is reported. Participants lost to follow-up were censored at the time of last assessment.
6 months
Graft Survival
Tijdsspanne: 6 months

Graft survival was defined as any participant who was known to have a functioning graft (i.e., not graft loss) at 6 months. Graft loss is defined as re-transplantation, nephrectomy, death or as dialysis ongoing at end of study or at discontinuation of the participant unless superseded by follow-up information.

The Kaplan-Meier estimate of graft survival within the first 6 months following transplantation is reported. Participants lost to follow-up were censored at the time of last assessment.
6 months
Maximum Histological Grade of All Biopsies After Local Review
Tijdsspanne: 6 months

The grade of acute rejection was classified according to Banff 97/05 updated version. If a patient had more than 1 rejection episode, the episode with the most severe grade was used.

Acute T-cell mediated rejection:

  • Grade IA: significant interstitial infiltration (>25% parenchyma affected) and foci of moderate tubulitis;
  • Grade IB: significant interstitial infiltration (>25% parenchyma affected) and foci of severe tubulitis;
  • Grade IIA: mild to moderate intimal arteritis;
  • Grade IIB: severe intimal arteritis comprising >25% of the luminal area;
  • Grade III: "transmural" arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells with accompanying lymphocyte inflammation.

Acute antibody-mediated rejection:

  • Grade I: acute tubular necrosis-like - complement split product positive (C4d+), minimal inflammation;
  • Grade II: capillary-margination and/or thromboses, C4d+
  • Grade III: arterial - v3, C4d+.
6 months
Percentage of Participants With Anti-Lymphocyte Antibody Therapy for Treatment of Rejection at Month 6
Tijdsspanne: 6 months
The Kaplan-Meier estimate of anti-lymphocyte antibody therapy for acute rejection (clinically-treated or biopsy-confirmed) within the first 6 months following transplantation is reported. Participants lost to follow-up or with missing outcomes were censored at their last follow-up visit.
6 months
Change From Month 1 in Serum Creatinine
Tijdsspanne: Month 1, 3, and 6
Month 1, 3, and 6
Change From Month 1 in Glomerular Filtration Rate (GFR)
Tijdsspanne: Month 1, 3, and 6
The GFR was calculated using the Modification of Diet in Renal Disease (MDRD) formula.
Month 1, 3, and 6
Change From Month 1 in Creatinine Clearance
Tijdsspanne: Month 1, 3, and 6
The creatinine clearance was calculated according to the Cockcroft-Gault formula.
Month 1, 3, and 6
GFR Measured by Iothalamate Clearance at Month 6
Tijdsspanne: Month 6
GFR measured using the iothalamate clearance method and determined by a central laboratory.
Month 6
Percentage of Participants With Efficacy Failure at Month 6
Tijdsspanne: 6 months

Efficacy failure is defined as death, graft loss, biopsy-confirmed acute T-cell mediated rejection assessed by local reading or lost to follow-up.

The Kaplan-Meier estimate of efficacy failure within the first 6 months following transplantation is reported.
6 months
Percentage of Participants With Delayed Graft Function
Tijdsspanne: 1 week
Delayed graft function was defined as the requirement for dialysis within the first week post-transplant.
1 week
Percentage of Participants With Treatment Failure at Month 6
Tijdsspanne: 6 months
Treatment failure is defined as efficacy failure (death, graft loss, biopsy-confirmed acute T-cell mediated rejection assessed by local reading, lost to follow-up) or early discontinuation of alefacept/placebo at any time (during the 12-week administration period) for any reason. The Kaplan-Meier estimate of treatment failure within the first 6 months following transplantation is reported. Participants lost to follow-up or with missing outcomes were censored at their last follow-up visit.
6 months
Number of Participants With Adverse Events
Tijdsspanne: 6 Months

Causally related was defined as adverse events (AEs) assessed by the Investigator as possibly or probably related to study drug or records where the relationship was missing.

A serious adverse event (SAE) was any untoward medical occurrence that, at any dose:

  • Resulted in death.
  • Was life-threatening.
  • Resulted in persistent or significant disability/incapacity.
  • Resulted in congenital anomaly or birth defect.
  • Required patient hospitalization or led to prolongation of hospitalization
  • Was considered a medically important event.

All rejections and any BK virus, Epstein Barr virus and/or cytomegalovirus infection had to be reported as an SAE
6 Months

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

Astellas Pharma Inc

Publicaties en nuttige links

De persoon die verantwoordelijk is voor het invoeren van informatie over het onderzoek stelt deze publicaties vrijwillig ter beschikking. Dit kan gaan over alles wat met het onderzoek te maken heeft.

Nuttige links

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start

1 december 2007

Primaire voltooiing (Werkelijk)

1 september 2009

Studie voltooiing (Werkelijk)

1 september 2009

Studieregistratiedata

Eerst ingediend

6 februari 2008

Eerst ingediend dat voldeed aan de QC-criteria

6 februari 2008

Eerst geplaatst (Schatting)

18 februari 2008

Updates van studierecords

Laatste update geplaatst (Schatting)

4 februari 2016

Laatste update ingediend die voldeed aan QC-criteria

5 januari 2016

Laatst geverifieerd

1 januari 2016

Meer informatie

Termen gerelateerd aan deze studie

Trefwoorden

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

  • 0485-CL-E201
  • 2007-002092-14 (EudraCT-nummer)

Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .

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