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

Kidney Transplantation Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02921789
• Other study ID #: 7163-CL-3201
• Status: Completed
• Phase: Phase 2
• Start date: May 22, 2017
• Est. completion date: May 18, 2021

Study information

• Verified date: June 2022
• Source: Astellas Pharma Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 67
• Est. completion date: May 18, 2021
• Est. primary completion date: December 11, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Glomerulosclerosis, Focal Segmental
• Kidney Transplantation
• Recurrence

Intervention

Drug:
• Bleselumab
Intravenous infusion
• Basiliximab
Bolus injection
• Mycophenolate Mofetil (MMF)
Oral Intravenous
• Tacrolimus Capsules
Oral Capsule
• Methylprednisone
Oral or Intravenous
• Prednisone
Oral Tablet

Locations

Country	Name	City	State
Canada	Site CA15002	Edmonton	Alberta
Canada	Site CA15006	Montreal	Quebec
Canada	Site CA15005	Vancouver	British Columbia
United States	Michigan Medicine	Ann Arbor	Michigan
United States	University of Colorado	Aurora	Colorado
United States	Erie County Medical Center	Buffalo	New York
United States	University of North Carolina	Chapel Hill	North Carolina
United States	Medical University of South Carolina	Charleston	South Carolina
United States	University of Virginia	Charlottesville	Virginia
United States	University of Chicago	Chicago	Illinois
United States	Duke University Medical Center	Durham	North Carolina
United States	Indiana University	Indianapolis	Indiana
United States	St. Barnabas	Livingston	New Jersey
United States	University of Louisville	Louisville	Kentucky
United States	University of Miami	Miami	Florida
United States	Tulane University Health Service Center	New Orleans	Louisiana
United States	Columbia University Medical Center	New York	New York
United States	Stanford School of Medicine	Palo Alto	California
United States	University of Pennsylvania Health System, PCAM	Philadelphia	Pennsylvania
United States	Washington University in St. Louis	Saint Louis	Missouri
United States	University of Utah Medical Center	Salt Lake City	Utah
United States	UCSF	San Francisco	California
United States	University of Arizona	Tucson	Arizona

Sponsors (2)

Lead Sponsor	Collaborator
Astellas Pharma Global Development, Inc.	Kyowa Kirin Co., Ltd.

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	At 3 Months post transplant
Secondary	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.	At 6 and 12 Months post transplant
Secondary	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.	At 3, 6 and 12 Months post transplant
Secondary	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.	12 Months post transplant
Secondary	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.	At 3, 6 and 12 Months post transplant

External Links

•   Link to plain language summary of the study on the Trial Results Summaries website
•   Link to results and other applicable study documents on the Astellas Clinical Trials website