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

NCT02921789 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 7163-CL-3201
• Study Type: interventional
• Target: 67
• Locations: 2 countries
• Sites: 23

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.

Conditions

Kidney Transplantation; Primary Focal Segmental Glomerulosclerosis (FSGS)

Keywords

Bleselumab; ASKP1240; Efficacy and Safety

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Percentage of Participants With rFSGS or Death or Graft Loss or Lost to Follow-up Through 6 and 12 Months Post Transplant

  At 6 and 12 Months post transplant

• Percentage of Participants With Biopsy-Proven Acute Rejection (BPAR) Through 3, 6, and 12 Months Post Transplant

  At 3, 6 and 12 Months post transplant

• Percentage of Participants With Efficacy Failure Through 12 Months Post Transplant

  12 Months post transplant

• Percentage of Participants With Biopsy Proven rFSGS Through 3, 6 and 12 Months Post-Transplant

  At 3, 6 and 12 Months post transplant

Study Arms (2)

Standard of Care (SOC) Regimen

ACTIVE COMPARATOR

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.

Drug: Basiliximab; Drug: Mycophenolate Mofetil (MMF); Drug: Tacrolimus Capsules; Drug: Methylprednisone; Drug: Prednisone

Bleselumab Regimen

EXPERIMENTAL

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.

Drug: Bleselumab; Drug: Basiliximab; Drug: Tacrolimus Capsules; Drug: Methylprednisone; Drug: Prednisone

Interventions

Bleselumab DRUG

Intravenous infusion

Also known as: ASKP1240

Bleselumab Regimen

Basiliximab DRUG

Bolus injection

Also known as: Simulect®

Bleselumab Regimen; Standard of Care (SOC) Regimen

Mycophenolate Mofetil (MMF) DRUG

Oral Intravenous

Also known as: CellCept®, MMF

Standard of Care (SOC) Regimen

Tacrolimus Capsules DRUG

Oral Capsule

Also known as: Prograf®

Bleselumab Regimen; Standard of Care (SOC) Regimen

Methylprednisone DRUG

Oral or Intravenous

Bleselumab Regimen; Standard of Care (SOC) Regimen

Prednisone DRUG

Oral Tablet

Bleselumab Regimen; Standard of Care (SOC) Regimen

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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 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.

Sponsors & Collaborators

• Astellas Pharma Global Development, Inc.: lead
• Kyowa Kirin Co., Ltd.: collaborator

Study Sites (23)

University of Arizona

Tucson, Arizona, 85724, United States

Location

Stanford School of Medicine

Palo Alto, California, 94304, United States

Location

UCSF

San Francisco, California, 94143, United States

Location

University of Colorado

Aurora, Colorado, 80045, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Indiana University

Indianapolis, Indiana, 46220, United States

Location

University of Louisville

Louisville, Kentucky, 40202, United States

Location

Tulane University Health Service Center

New Orleans, Louisiana, 70112, United States

Location

Michigan Medicine

Ann Arbor, Michigan, 48109, United States

Location

Washington University in St. Louis

St Louis, Missouri, 63110, United States

Location

St. Barnabas

Livingston, New Jersey, 07039, United States

Location

Erie County Medical Center

Buffalo, New York, 14215, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

University of North Carolina

Chapel Hill, North Carolina, 27713, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

University of Pennsylvania Health System, PCAM

Philadelphia, Pennsylvania, 19104, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

University of Utah Medical Center

Salt Lake City, Utah, 84132, United States

Location

University of Virginia

Charlottesville, Virginia, 22908, United States

Location

Site CA15002

Edmonton, Alberta, TG6 2B7, Canada

Location

Site CA15005

Vancouver, British Columbia, V6Z 1Y6, Canada

Location

Site CA15006

Montreal, Quebec, H1T 2M4, Canada

Location

Related Publications (1)

• Shoji J, Goggins WC, Wellen JR, Cunningham PN, Johnston O, Chang SS, Solez K, Santos V, Larson TJ, Takeuchi M, Wang X. Efficacy and Safety of Bleselumab in Preventing the Recurrence of Primary Focal Segmental Glomerulosclerosis in Kidney Transplant Recipients: A Phase 2a, Randomized, Multicenter Study. Transplantation. 2024 Aug 1;108(8):1782-1792. doi: 10.1097/TP.0000000000004985. Epub 2024 Jul 20.

  PMID: 39042770 DERIVED

Related Links

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

MeSH Terms

Interventions

bleselumab; Basiliximab; Mycophenolic Acid; Tacrolimus; Prednisone

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids; Macrolides; Lactones; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Clinical Trial Disclosure
• Organization: Astellas Pharma Global Development, Inc

astellas.resultsdisclosure@astellas.com

800-888-7704

Study Officials

• Medical Director

  Astellas Pharma Global Development, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 30, 2016
• First Posted: October 3, 2016
• Study Start: May 22, 2017
• Primary Completion: December 11, 2020
• Study Completion: May 18, 2021
• Last Updated: December 4, 2024
• Results First Posted: January 5, 2022

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• 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.
• 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.

Locations

CA (3); US (20)