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Study to Assess the Efficacy and Safety of Bleselumab in Preventing the Recurrence of Focal Segmental Glomerulosclerosis in de Novo Kidney Transplant Recipients

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ClinicalTrials.gov Identifier: NCT02921789
Recruitment Status : Recruiting
First Posted : October 3, 2016
Last Update Posted : July 30, 2018
Sponsor:
Collaborator:
Kyowa Hakko Kirin Co., Ltd
Information provided by (Responsible Party):
Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )

Brief Summary:
The purpose of this study is 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 will be imputed as rFSGS.

Condition or disease Intervention/treatment Phase
Kidney Transplantation Focal Segmental Glomerulosclerosis (FSGS) Drug: Bleselumab Drug: Basiliximab Drug: Mycophenolate Mofetil (MMF) Drug: Tacrolimus Capsules Drug: Methylprednisone Drug: Prednisone Phase 2

Detailed Description:
The study will consist 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 will enter into a Screening Period (Days -21 to -1 prior to transplant), undergo a Transplant (Day 0 [zero]), and are then to be followed for up to 12 months in the Post-Transplant Period (Day 0 through 12 months post-transplant).

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : May 22, 2017
Estimated Primary Completion Date : September 2019
Estimated Study Completion Date : May 2020


Arm Intervention/treatment
Active Comparator: Standard of Care Regimen
Standard of Care regimen (basiliximab induction, tacrolimus, methylprednisone, prednisone and MMF).
Drug: Basiliximab
Bolus injections
Other Name: Simulect®

Drug: Mycophenolate Mofetil (MMF)
Oral (po) or intravenous (iv) two times a day (bid)
Other Names:
  • CellCept®
  • MMF

Drug: Tacrolimus Capsules
Oral (po) or intravenous (iv) if medically indicated
Other Name: Prograf®

Drug: Methylprednisone
Oral (po) or intravenous (iv)

Drug: Prednisone
Oral (po)

Experimental: Bleselumab Regimen
Bleselumab regimen (basiliximab, methylprednisone, prednisone, bleselumab and tacrolimus).
Drug: Bleselumab
Intravenous infusion
Other Name: ASKP1240

Drug: Basiliximab
Bolus injections
Other Name: Simulect®

Drug: Tacrolimus Capsules
Oral (po) or intravenous (iv) if medically indicated
Other Name: Prograf®

Drug: Methylprednisone
Oral (po) or intravenous (iv)

Drug: Prednisone
Oral (po)




Primary Outcome Measures :
  1. Recurrence of focal segmental glomerulosclerosis (FSGS) defined as nephrotic range proteinuria with protein-creatinine ratio (≥ 3.0 g/g) through 3 months post-transplant. Deaths, graft loss and lost to follow-up will be imputed as rFSGS. [ Time Frame: Up to 3 months post-transplant ]
    All episodes of kidney dysfunction based on clinical signs and symptoms will be evaluated by a biopsy at the local pathological laboratory for recurrence of FSGS and for possible rejection. The same slides and images of the biopsy will also be sent to a central pathology lab and read by an independent pathologist to determine recurrence of FSGS.


Secondary Outcome Measures :
  1. Recurrence of FSGS defined as nephrotic range proteinuria with protein-creatinine ratio (≥ 3.0 g/g). Deaths, graft loss and lost to follow-up will be imputed as rFSGS. [ Time Frame: Up to 12 months post-transplant ]
    All episodes of kidney dysfunction based on clinical signs and symptoms will be evaluated by a biopsy at the local pathological laboratory for recurrence of FSGS and for possible rejection. The same slides and images of the biopsy will also be sent to a central pathology lab and read by an independent pathologist to determine recurrence of FSGS.

  2. Biopsy-proven acute rejection (BPAR) (Banff Grade ≥ 1, local read) [ Time Frame: Up to 12 months post-transplant ]
    All episodes of kidney dysfunction based on clinical signs and symptoms will be evaluated for possible rejection. All subjects should have biopsy confirmation of rejection before treatment is begun or within 48 hours of initiation of treatment for acute rejection. The pathologist at the clinical site will grade all biopsies using the 2007 Banff criteria (Grading of Acute Kidney Allograft Rejection). Biopsy-proven acute rejection (BPAR, T- or B-cell) will be determined by local review.

  3. Efficacy failure [ Time Frame: Up to 12 months post-transplant ]
    Efficacy failure defined as BPAR (Banff Grade ≥ 1; local read), death, graft loss, or lost to follow-up

  4. Biopsy-proven (blinded, central read) rFSGS [ Time Frame: Up to 12 months post-transplant ]
    Biopsy-proven rFSGS will include only those for whom slides are reviewed by the independent pathologist who will be the blinded, central reader. All subjects are required to provide a biopsy either after the appearance of symptoms for rejection or rFSGS, or at the day 90/month 3 visit, if there has not been a previous biopsy indicating rFSGS in the transplanted kidney. The blinded, central reader will objectively assess podocyte changes to identify those with rFSGS.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02921789


Contacts
Contact: Astellas Pharma Global Development - US 800-888-7704 astellas.registration@astellas.com

  Show 36 Study Locations
Sponsors and Collaborators
Astellas Pharma Global Development, Inc.
Kyowa Hakko Kirin Co., Ltd
Investigators
Study Director: Medical Director Astellas Pharma Global Development, Inc.

Responsible Party: Astellas Pharma Global Development, Inc.
ClinicalTrials.gov Identifier: NCT02921789     History of Changes
Other Study ID Numbers: 7163-CL-3201
First Posted: October 3, 2016    Key Record Dates
Last Update Posted: July 30, 2018
Last Verified: July 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. ):
Bleselumab
ASKP1240
Efficacy and Safety

Additional relevant MeSH terms:
Recurrence
Glomerulosclerosis, Focal Segmental
Disease Attributes
Pathologic Processes
Glomerulonephritis
Nephritis
Kidney Diseases
Urologic Diseases
Prednisone
Mycophenolic Acid
Tacrolimus
Basiliximab
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Calcineurin Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antibiotics, Antineoplastic
Antibiotics, Antitubercular
Antitubercular Agents
Anti-Bacterial Agents
Anti-Infective Agents