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

5 janvier 2016 mis à jour par: 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.

Aperçu de l'étude

Statut

Complété

Les conditions

Intervention / Traitement

Type d'étude

Interventionnel

Inscription (Réel)

218

Phase

  • Phase 2

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Lieux d'étude

  • Allemagne
      • Bochum, Allemagne, 44892
      • Regensburg, Allemagne, 93053
  • Belgique
      • Bruxelles, Belgique, 1070
      • Bruxelles, Belgique, 1200
      • Gent, Belgique, 9000
      • Leuven, Belgique, 3000
      • Liege, Belgique, 4000
  • Espagne
      • Barcelona, Espagne, 8036
      • Llobregat, Espagne, 8907
      • Madrid, Espagne, 28041
      • Malaga, Espagne, 29010
      • Santander, Espagne, 39008
  • France
      • Creteil, France, 94010
      • Le Kremlin Bicetre Cedex, France, 94275
      • Montpellier, France, 34295
      • Nantes Cedex 1, France, 44093
      • Nice Cedex 1, France, 6002
      • Paris, France, 75475
      • Toulouse Cedex, France, 31054
  • Hongrie
      • Budapest, Hongrie, 1082
  • Italie
      • Bologna, Italie, 40138
      • Padova, Italie, 35128
      • Rome, Italie, 00168
      • Siena, Italie, 53100
  • L'Autriche
      • Vienna, L'Autriche, 1090
  • Pays-Bas
      • Maastricht, Pays-Bas, 6229
  • Pologne
      • Bydgoszcz, Pologne, 85-094
      • Poznan, Pologne, 60-479
      • Szczecin, Pologne, 70-111
  • Royaume-Uni
      • Manchester, Royaume-Uni, M13 9WL
  • République tchèque
      • Praha, République tchèque, 140 21
  • Suède
      • Goteborg, Suède, 41345
      • Uppsala, Suède, 75185

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

18 ans à 64 ans (Adulte)

Accepte les volontaires sains

Non

Sexes éligibles pour l'étude

Tout

La description

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

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: La prévention
  • Répartition: Randomisé
  • Modèle interventionnel: Affectation parallèle
  • Masquage: Quadruple

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Comparateur placebo: 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.
Médicament: placebo
IV and subcutaneous injection
Médicament: Tacrolimus
The initial daily dose was 0.2 mg/kg orally given in 2 doses commencing 24 hours after completion of surgery.
Médicament: Mycophenolate Mofetil
Mycophenolic mofetil was administered as 750 mg twice per day orally
Médicament: 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
Expérimental: 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.
Médicament: Tacrolimus
The initial daily dose was 0.2 mg/kg orally given in 2 doses commencing 24 hours after completion of surgery.
Médicament: Mycophenolate Mofetil
Mycophenolic mofetil was administered as 750 mg twice per day orally
Médicament: 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

Médicament: Alefacept
IV and subcutaneous injection
Autres noms:
  • Amevive

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Percentage of Participants With Biopsy-confirmed Acute T-cell Mediated Rejection at Month 6 Assessed by Local Review
Délai: 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

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Percentage of Participants With Biopsy Confirmed Antibody-Mediated Acute Rejection at Month 6
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: Month 1, 3, and 6
Month 1, 3, and 6
Change From Month 1 in Glomerular Filtration Rate (GFR)
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

Astellas Pharma Inc

Publications et liens utiles

La personne responsable de la saisie des informations sur l'étude fournit volontairement ces publications. Il peut s'agir de tout ce qui concerne l'étude.

Liens utiles

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude

1 décembre 2007

Achèvement primaire (Réel)

1 septembre 2009

Achèvement de l'étude (Réel)

1 septembre 2009

Dates d'inscription aux études

Première soumission

6 février 2008

Première soumission répondant aux critères de contrôle qualité

6 février 2008

Première publication (Estimation)

18 février 2008

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Estimation)

4 février 2016

Dernière mise à jour soumise répondant aux critères de contrôle qualité

5 janvier 2016

Dernière vérification

1 janvier 2016

Plus d'information

Termes liés à cette étude

Mots clés

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

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

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

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