A Study to Assess the Efficacy and Safety of ASKP1240 in de Novo Kidney Transplant Recipients

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and safety of ASKP1240, an anti-CD40 monoclonal antibody, for the prophylaxis of organ rejection after kidney transplantation. This study will compare the efficacy of basiliximab induction, ASKP1240, mycophenolate mofetil (MMF), and steroids [calcineurin inhibitor (CNI) avoidance] to the standard of care immunosuppressive regimen (basiliximab induction + tacrolimus + MMF + steroids). In addition, the study will compare the efficacy of basiliximab induction, ASKP1240, tacrolimus and steroids [CNI minimization-MMF avoidance] to the standard of care immunosuppressive regimen (basiliximab induction + tacrolimus + MMF + steroids).

Detailed Description
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Subjects will be followed for 6 months. Upon completion of the first 6 months of the study, subjects may participate in the Long Term Extension period of the study. Subjects will remain on their original treatment arm up to three years post-transplant (and / or Sponsor discontinues development or the subject no longer wishes to participate in the study).

Official Title
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A Phase 2a, Randomized, Open-label, Active Control, Multi-Center Study to Assess the Efficacy and Safety of ASKP1240 in de Novo Kidney Transplant Recipients

Conditions
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Kidney Transplantation

Intervention / Treatment
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* Drug: ASKP1240
* Drug: Tacrolimus
* Drug: Mycophenolate Mofetil (MMF)
* Drug: Basiliximab
* Drug: Methylprednisone
* Drug: Prednisone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is a recipient of a de novo kidney from a living or deceased donor Exclusion Criteria: Subject has induction therapy, other than study-assigned basiliximab, planned as part of initial immunosuppressive regimen Subject has previously received or is receiving an organ transplant other than a kidney Subject will receive a solitary kidney from a deceased donor < 5 years of age Subject will receive a kidney with an anticipated cold ischemia time (CIT) of > 30 hours Subject will receive a kidney that meets both Extended Criteria Donor (ECD) and Donation after Cardiac Death (DCD) criteria. Note: a kidney that meets either ECD or DCD criteria is eligible for inclusion Subject will receive an ABO incompatible donor kidney Subject has a current calculated panel reactive antibody (cPRA) level >50%

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard of Care<br>Basiliximab induction + Tacrolimus + MMF + Corticosteroids | Drug: Tacrolimus<br>* intravenous or oral<br>* Other names: Prograf®;Drug: Mycophenolate Mofetil (MMF)<br>* intravenous or oral<br>* Other names: CellCept®;Drug: Basiliximab<br>* intravenous<br>* Other names: Simulect®;Drug: Methylprednisone<br>* Intravenous<br>Drug: Prednisone<br>* Oral<br>|
| Experimental: CNI avoidance<br>Basiliximab induction + ASKP1240 + MMF + Corticosteroids | Drug: ASKP1240<br>* intravenous infusion<br>Drug: Mycophenolate Mofetil (MMF)<br>* intravenous or oral<br>* Other names: CellCept®;Drug: Basiliximab<br>* intravenous<br>* Other names: Simulect®;Drug: Methylprednisone<br>* Intravenous<br>Drug: Prednisone<br>* Oral<br>|
| Experimental: CNI minimization-MMF avoidance<br>Basiliximab induction + ASKP1240 + Tacrolimus + Corticosteroids | Drug: ASKP1240<br>* intravenous infusion<br>Drug: Tacrolimus<br>* intravenous or oral<br>* Other names: Prograf®;Drug: Basiliximab<br>* intravenous<br>* Other names: Simulect®;Drug: Methylprednisone<br>* Intravenous<br>Drug: Prednisone<br>* Oral<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biopsy-proven acute (T or B cell) rejection (BPAR) (Banff 2007 Grade ≥ 1) by local review |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glomerular Filtration Rate (GFR) | GFR is based on Modification of Diet in Renal Disease (4 variable-MDRD) criteria | 6 months | 
| Patient Survival | Subject survival is defined as any subject who does not die during the study. | 6 months | 
| Graft Survival | Graft survival is defined as any subject who does not experience graft loss during the study. Graft loss is defined as subject death, retransplantation, transplant nephrectomy, or the permanent return to dialysis (greater than 30 days). | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Kidney Transplantation, de novo Kidney Transplantation, ASKP1240