search
Back to results

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

Primary Purpose

Kidney Transplantation, Primary Focal Segmental Glomerulosclerosis (FSGS)

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Bleselumab
Basiliximab
Mycophenolate Mofetil (MMF)
Tacrolimus Capsules
Methylprednisone
Prednisone
Sponsored by
Astellas Pharma Global Development, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Kidney Transplantation focused on measuring Bleselumab, ASKP1240, Efficacy and Safety

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Arizona
  • Stanford School of Medicine
  • UCSF
  • University of Colorado
  • University of Miami
  • University of Chicago
  • Indiana University
  • University of Louisville
  • Tulane University Health Service Center
  • Michigan Medicine
  • Washington University in St. Louis
  • St. Barnabas
  • Erie County Medical Center
  • Columbia University Medical Center
  • University of North Carolina
  • Duke University Medical Center
  • University of Pennsylvania Health System, PCAM
  • Medical University of South Carolina
  • University of Utah Medical Center
  • University of Virginia
  • Site CA15002
  • Site CA15005
  • Site CA15006

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Standard of Care (SOC) Regimen

Bleselumab Regimen

Arm Description

Participants received SOC regimen (basiliximab induction, MMF, Tacrolimus, Methylprednisone, Prednisolone). Basiliximab 20 milligrams (mg) administered by intravenous injection prior to transplantation or intra- operatively before revascularisation as induction therapy and 20mg on day 3 or 4 or 5 post-transplant. MMF 1 gram (g) administered orally or intravenously twice daily until 12 months post transplant. Tacrolimus 0.1 milligram per kilogram per day (mg/kg/day) (two equally divided doses at 0.05 mg/kg/day every 12 hours with a target trough level of 4 - 11 nanogram per milliliter (ng/mL) administered orally within 48 hours post-transplant until 12 months post transplant. Methylprednisone 500, 250, 125 and 60mg administered orally or intravenously on days 0, 1, 2 and 3 respectively and continue through 12 months post transplant. Prednisolone administered orally by tapered doses of 20-30 mg on days 4-14, 10-20mg on days 15-28, 5-10mg on days 29 through 12 months post transplant.

Participants received bleselumab regimen (basiliximab induction, bleselumab, Tacrolimus, Methylprednisone, Prednisolone). Basiliximab 20mg administered by intravenous injection prior to transplantation or intra - operatively before revascularisation as induction therapy and 20mg on day 3 or 4 or 5 post-transplant. Bleselumab 200mg administered by intravenous infusion on day 0, 7, 14, 28, 42, 56, 70, 90 and once per month until month 12. Tacrolimus 0.1 mg/kg/day (two equally divided doses at 0.05 mg/kg/day every 12 hours with a target trough level of 4 - 11 ng/mL) administered orally within 48 hours post transplant until 12 months post transplant. Methylprednisone 500, 250, 125 and 60mg administered orally or intravenously on days 0, 1, 2 and 3 respectively and continue through 12 months post transplant. Prednisolone administered orally by tapered doses of 20-30 mg on days 4-14, 10-20mg on days 15-28, 5-10mg on days 29 through 12 months post transplant.

Outcomes

Primary Outcome Measures

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
rFSGS was defined as nephrotic range proteinuria with a protein/creatinine ratio (≥ 3.0 g/g). Death, graft loss or lost to follow-up was imputed as rFSGS.

Secondary Outcome Measures

Percentage of Participants With rFSGS or Death or Graft Loss or Lost to Follow-up Through 6 and 12 Months Post Transplant
rFSGS was defined as nephrotic range proteinuria with a protein/creatinine ratio (≥ 3.0 g/g). Death, graft loss or lost to follow-up was imputed as rFSGS.
Percentage of Participants With Biopsy-Proven Acute Rejection (BPAR) Through 3, 6, and 12 Months Post Transplant
All episodes of kidney dysfunction based on clinical signs and symptoms were evaluated for possible BPAR. BPAR was confirmed if participants Banff criteria >=1.
Percentage of Participants With Efficacy Failure Through 12 Months Post Transplant
Efficacy failure was defined as BPAR, death, graft loss or lost to follow-up through 12 months post transplant.
Percentage of Participants With Biopsy Proven rFSGS Through 3, 6 and 12 Months Post-Transplant
Percentage of participants with biopsy-proven rFSGS determined by a blinded central review of images from electron microscopy (EM) and slides for light microscopy (LM) by an independent pathologist.

Full Information

First Posted
September 30, 2016
Last Updated
June 10, 2022
Sponsor
Astellas Pharma Global Development, Inc.
Collaborators
Kyowa Kirin Co., Ltd.
search

1. Study Identification

Unique Protocol Identification Number
NCT02921789
Brief Title
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

2. Study Status

Record Verification Date
June 2022
Overall Recruitment Status
Completed
Study Start Date
May 22, 2017 (Actual)
Primary Completion Date
December 11, 2020 (Actual)
Study Completion Date
May 18, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Astellas Pharma Global Development, Inc.
Collaborators
Kyowa Kirin Co., Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Kidney Transplantation, Primary Focal Segmental Glomerulosclerosis (FSGS)
Keywords
Bleselumab, ASKP1240, Efficacy and Safety

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
67 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Standard of Care (SOC) Regimen
Arm Type
Active Comparator
Arm Description
Participants received SOC regimen (basiliximab induction, MMF, Tacrolimus, Methylprednisone, Prednisolone). Basiliximab 20 milligrams (mg) administered by intravenous injection prior to transplantation or intra- operatively before revascularisation as induction therapy and 20mg on day 3 or 4 or 5 post-transplant. MMF 1 gram (g) administered orally or intravenously twice daily until 12 months post transplant. Tacrolimus 0.1 milligram per kilogram per day (mg/kg/day) (two equally divided doses at 0.05 mg/kg/day every 12 hours with a target trough level of 4 - 11 nanogram per milliliter (ng/mL) administered orally within 48 hours post-transplant until 12 months post transplant. Methylprednisone 500, 250, 125 and 60mg administered orally or intravenously on days 0, 1, 2 and 3 respectively and continue through 12 months post transplant. Prednisolone administered orally by tapered doses of 20-30 mg on days 4-14, 10-20mg on days 15-28, 5-10mg on days 29 through 12 months post transplant.
Arm Title
Bleselumab Regimen
Arm Type
Experimental
Arm Description
Participants received bleselumab regimen (basiliximab induction, bleselumab, Tacrolimus, Methylprednisone, Prednisolone). Basiliximab 20mg administered by intravenous injection prior to transplantation or intra - operatively before revascularisation as induction therapy and 20mg on day 3 or 4 or 5 post-transplant. Bleselumab 200mg administered by intravenous infusion on day 0, 7, 14, 28, 42, 56, 70, 90 and once per month until month 12. Tacrolimus 0.1 mg/kg/day (two equally divided doses at 0.05 mg/kg/day every 12 hours with a target trough level of 4 - 11 ng/mL) administered orally within 48 hours post transplant until 12 months post transplant. Methylprednisone 500, 250, 125 and 60mg administered orally or intravenously on days 0, 1, 2 and 3 respectively and continue through 12 months post transplant. Prednisolone administered orally by tapered doses of 20-30 mg on days 4-14, 10-20mg on days 15-28, 5-10mg on days 29 through 12 months post transplant.
Intervention Type
Drug
Intervention Name(s)
Bleselumab
Other Intervention Name(s)
ASKP1240
Intervention Description
Intravenous infusion
Intervention Type
Drug
Intervention Name(s)
Basiliximab
Other Intervention Name(s)
Simulect®
Intervention Description
Bolus injection
Intervention Type
Drug
Intervention Name(s)
Mycophenolate Mofetil (MMF)
Other Intervention Name(s)
CellCept®, MMF
Intervention Description
Oral Intravenous
Intervention Type
Drug
Intervention Name(s)
Tacrolimus Capsules
Other Intervention Name(s)
Prograf®
Intervention Description
Oral Capsule
Intervention Type
Drug
Intervention Name(s)
Methylprednisone
Intervention Description
Oral or Intravenous
Intervention Type
Drug
Intervention Name(s)
Prednisone
Intervention Description
Oral Tablet
Primary Outcome Measure Information:
Title
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
Description
rFSGS was defined as nephrotic range proteinuria with a protein/creatinine ratio (≥ 3.0 g/g). Death, graft loss or lost to follow-up was imputed as rFSGS.
Time Frame
At 3 Months post transplant
Secondary Outcome Measure Information:
Title
Percentage of Participants With rFSGS or Death or Graft Loss or Lost to Follow-up Through 6 and 12 Months Post Transplant
Description
rFSGS was defined as nephrotic range proteinuria with a protein/creatinine ratio (≥ 3.0 g/g). Death, graft loss or lost to follow-up was imputed as rFSGS.
Time Frame
At 6 and 12 Months post transplant
Title
Percentage of Participants With Biopsy-Proven Acute Rejection (BPAR) Through 3, 6, and 12 Months Post Transplant
Description
All episodes of kidney dysfunction based on clinical signs and symptoms were evaluated for possible BPAR. BPAR was confirmed if participants Banff criteria >=1.
Time Frame
At 3, 6 and 12 Months post transplant
Title
Percentage of Participants With Efficacy Failure Through 12 Months Post Transplant
Description
Efficacy failure was defined as BPAR, death, graft loss or lost to follow-up through 12 months post transplant.
Time Frame
12 Months post transplant
Title
Percentage of Participants With Biopsy Proven rFSGS Through 3, 6 and 12 Months Post-Transplant
Description
Percentage of participants with biopsy-proven rFSGS determined by a blinded central review of images from electron microscopy (EM) and slides for light microscopy (LM) by an independent pathologist.
Time Frame
At 3, 6 and 12 Months post transplant

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Astellas Pharma Global Development, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
University of Arizona
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85724
Country
United States
Facility Name
Stanford School of Medicine
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States
Facility Name
UCSF
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
University of Colorado
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
University of Miami
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
University of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Indiana University
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46220
Country
United States
Facility Name
University of Louisville
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40202
Country
United States
Facility Name
Tulane University Health Service Center
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70112
Country
United States
Facility Name
Michigan Medicine
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
Washington University in St. Louis
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
St. Barnabas
City
Livingston
State/Province
New Jersey
ZIP/Postal Code
07039
Country
United States
Facility Name
Erie County Medical Center
City
Buffalo
State/Province
New York
ZIP/Postal Code
14215
Country
United States
Facility Name
Columbia University Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
University of North Carolina
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27713
Country
United States
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
University of Pennsylvania Health System, PCAM
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Medical University of South Carolina
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States
Facility Name
University of Utah Medical Center
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84132
Country
United States
Facility Name
University of Virginia
City
Charlottesville
State/Province
Virginia
ZIP/Postal Code
22908
Country
United States
Facility Name
Site CA15002
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
TG6 2B7
Country
Canada
Facility Name
Site CA15005
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V6Z 1Y6
Country
Canada
Facility Name
Site CA15006
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H1T 2M4
Country
Canada

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as compounds terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Conditions and exceptions are described under the Sponsor Specific Details for Astellas on ww.clinicalstudydatarequest.com.
IPD Sharing Time Frame
Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data.
IPD Sharing Access Criteria
Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.
IPD Sharing URL
https://www.clinicalstudydatarequest.com/
Links:
URL
https://www.clinicaltrials.astellas.com/study/?pid=7163-CL-3201
Description
Link to results and other applicable study documents on the Astellas Clinical Trials website
URL
https://www.trialsummaries.com/Study/StudyDetails?id=14809&tenant=MT_AST_9011
Description
Link to plain language summary of the study on the Trial Results Summaries website

Learn more about this trial

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

We'll reach out to this number within 24 hrs