Clinical trial NCT02921789: Study to Assess the Efficacy and Safety of Bleselumab in Preventing the Recurrence of Focal Segmental Glomerulosclerosis in de Novo Kidney Transplant Recipients
Official title: A Phase 2a, Randomized, Open-Label, Active Control, Multi-Center Study to Assess the Efficacy and Safety of Bleselumab in Preventing the Recurrence of Focal Segmental Glomerulosclerosis in de Novo Kidney Transplant Recipients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Kidney Transplantation
Primary Focal Segmental Glomerulosclerosis (FSGS)
Keywords: Bleselumab
ASKP1240
Efficacy and Safety
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
Collaborators: name: Kyowa Kirin Co., Ltd.
First posted: 2016-10-03
Enrollment: 67
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study was to assess the efficacy of the bleselumab regimen (basiliximab induction, tacrolimus, steroids and bleselumab) compared with the Standard of Care (SOC) regimen (basiliximab induction, tacrolimus, steroids and mycophenolate mofetil \[MMF\]) in the prevention of recurrent Focal Segmental Glomerulosclerosis (rFSGS) defined as nephrotic range proteinuria with protein-creatinine ratio (≥ 3.0 g/g) through 3 months post-transplant. Death, graft loss or lost to follow-up were imputed as rFSGS.

Detailed description: The study consisted of the following periods: Screening (Days -21 to -1), Transplant (Day 0), Post-Transplant (Day 0/post-skin closure through 12 months post-transplant). All subjects entered into a Screening Period (Days -21 to -1 prior to transplant), and underwent a Transplant (Day 0 \[zero\]), and then followed for up to 12 months in the Post-Transplant Period (Day 0 through 12 months post-transplant).

Eligibility criteria: Inclusion Criteria:

* Subject is a recipient of a de novo kidney from a living or deceased donor and has biopsy-proven, primary FSGS (pFSGS) as a cause of end stage renal disease (ESRD) in the subject's native kidneys (initial diagnosing biopsy report is required). A subject who has biopsy-proven pFSGS as a cause of ESRD, and the subject's most current graft failure(s) is due to the recurrence of FSGS, is eligible.
* Subject is anticipated to receive first oral dose of tacrolimus within 48 hours of transplant procedure.
* Subject must be willing and able to comply with the study requirements including prohibited concomitant medication restrictions.
* Subject agrees not to participate in another interventional study while on treatment.

Exclusion Criteria:

* Subject has Induction therapy, other than study-assigned basiliximab, planned as part of initial immunosuppressive regimen.
* Subject has a diagnosis of secondary FSGS (familial, virus associated, medication, etc.) or a defined genetic cause of FSGS.
* Subject has previously received any organ transplant including a kidney and the most current graft failure(s) is not due to the recurrence of FSGS.
* Subject will receive a kidney as part of a multi-organ transplant.
* Subject will receive a dual kidney transplant from a deceased donor.
* 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. (A kidney that meets either ECD OR DCD criteria may be eligible for inclusion.)
* Subject will receive a blood group system (A, AB, B, O, ABO) incompatible (including A2 into B or O) donor kidney.
* Recipient or donor is known to be seropositive for human immuno-deficiency virus (HIV).
* Subject has a current calculated panel reactive antibody (cPRA) level \> 50%.
* Subject has a current malignancy or a history of malignancy (within the past 5 years), except nonmetastatic basal or squamous cell carcinoma of the skin that has been treated successfully, or a renal cell carcinoma that has been treated successfully more than 2 years prior to transplantation.
* Subject has significant liver disease, defined as having during the past 21 days consistently elevated aspartate aminotransferase (AST) (SGOT) and/or alanine aminotransferase (ALT) (SGPT) levels greater than 1.5 times the upper value of the normal range of the investigational site.
* Subject is known to have a positive test for latent tuberculosis (TB) and has not previously received adequate anti-microbial therapy/or would require TB prophylaxis after transplant.
* Subject has an uncontrolled concomitant infection or any other unstable medical condition that could interfere with the study objectives.
* Subject is concurrently participating in another drug study or has received an investigational drug up to 30 days or 5 half-lives prior to transplant.
* Subject is currently receiving or has received up to 8 weeks prior to transplant an immunologic biologic compound (i.e., tumor necrosis factor (TNF) inhibitors, \[e.g., etanercept, adalimumab\], intravenous immunoglobulin (IVIG)). A subject who has previously received a kidney organ transplant and is currently on an immunosuppression regimen that includes MMF, or any of its components, must discontinue MMF.
* Subject has previously received bleselumab or participated in a clinical study with bleselumab.
* Subject has a known hypersensitivity to tacrolimus, MMF, basiliximab, corticosteroids, or any of the components.
* Subject has any form of substance abuse, psychiatric disorder, or a condition that could invalidate communication with the Investigator.
* Subject has a clinically significant abnormal electrocardiogram (ECG) at Screening.
* Subject is unlikely to comply with the visits scheduled in the protocol

Primary outcomes:
measure: Percentage of Participants With Recurrence of Focal Segmental Glomerulosclerosis (rFSGS) or Death or Graft Loss or Lost to Follow-up Through 3 Months Post Transplant
timeFrame: At 3 Months post transplant
Secondary outcomes:
measure: Percentage of Participants With rFSGS or Death or Graft Loss or Lost to Follow-up Through 6 and 12 Months Post Transplant
timeFrame: At 6 and 12 Months post transplant
measure: Percentage of Participants With Biopsy-Proven Acute Rejection (BPAR) Through 3, 6, and 12 Months Post Transplant
timeFrame: At 3, 6 and 12 Months post transplant
measure: Percentage of Participants With Efficacy Failure Through 12 Months Post Transplant
timeFrame: 12 Months post transplant
measure: Percentage of Participants With Biopsy Proven rFSGS Through 3, 6 and 12 Months Post-Transplant
timeFrame: At 3, 6 and 12 Months post transplant
Other outcomes:
Locations:
city: Tucson
country: United States
facility: University of Arizona
state: Arizona
city: Palo Alto
country: United States
facility: Stanford School of Medicine
state: California
city: San Francisco
country: United States
facility: UCSF
state: California
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Louisville
country: United States
facility: University of Louisville
state: Kentucky
city: New Orleans
country: United States
facility: Tulane University Health Service Center
state: Louisiana
city: Ann Arbor
country: United States
facility: Michigan Medicine
state: Michigan
city: Saint Louis
country: United States
facility: Washington University in St. Louis
state: Missouri
city: Livingston
country: United States
facility: St. Barnabas
state: New Jersey
city: Buffalo
country: United States
facility: Erie County Medical Center
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Philadelphia
country: United States
facility: University of Pennsylvania Health System, PCAM
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Salt Lake City
country: United States
facility: University of Utah Medical Center
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Edmonton
country: Canada
facility: Site CA15002
state: Alberta
city: Vancouver
country: Canada
facility: Site CA15005
state: British Columbia
city: Montreal
country: Canada
facility: Site CA15006
state: Quebec
Study officials:
affiliation: Astellas Pharma Global Development, Inc.
name: Medical Director
role: STUDY_DIRECTOR
References: