Selective CD28 Blockade in Renal Transplant Recipients

NCT04903054 | Withdrawn Phase 2 DMC FDA Drug

• 3 other identifiers: DAIT RTB-011U01AI138909NIAID CRMS ID#: 38687
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this study is to evaluate the safety and efficacy of lulizumab, a CD28-specific domain antibody (CD28 dAb), compared to tacrolimus, as the primary immunosuppressant in first-time renal transplant recipients.

Conditions

Kidney Transplantation; Renal Transplant Recipients

Keywords

CD28 blockade; Cluster of Differentiation (CD); CNI inhibition; immune modulation; rejection

Outcome Measures

Primary Outcomes (1)

• Mean Estimated Glomerular Filtration rate (eGFR) (MDRD)

  Efficacy measure. Glomerular Filtration Rate (GFR) will be estimated using the Modification of Diet in Renal Disease (MDRD) equation. MDRD is an equation (calculation) used to estimate GFR in participants with impaired renal function based on serum creatinine, age, race, and gender.

  From Month 2 to Month 12 Post Transplantation

Secondary Outcomes (24)

• Proportion of Participants Who Remain Free of Biopsy Proven Acute T-Cell Mediated Rejection (aTCMR)

  Up to 15 Months Post Transplantation

• Proportion of Participants Who Remain Free of Antibody-Mediated Rejection (ABMR)

  Up to 15 Months Post Transplantation

• Cumulative Incidence of Serious Adverse Events

  Up to 15 Months Post Transplantation

• Incidence of Serious Infection(s) of Special Interest

  Up to 15 Months Post Transplantation

• Incidence of Cytomegalovirus (CMV) Viremia

  Up to 15 Months Post Transplantation

Study Arms (2)

Lulizumab + SOC

EXPERIMENTAL

N=27 participants will receive a loading dose of lulizumab on Day 0, the day of surgery. This will be followed by a maintenance dose administered on a weekly basis (weeks 1 through 26 post-transplant), followed by administration every two weeks (weeks 28 through 52 post-transplant). Method of administration: subcutaneously. Dose unit of measure: milligrams (mgs). Plus (+) Standard of Care (SOC) Regimen, per protocol- Renal transplant recipients will receive FDA-approved, immunosuppressive medications according to standard of care at Emory Transplant Center: * Induction Thymoglobulin: Administered intravenously, dose unit of measure: mgs. * Induction Methylprednisolone: Administered intravenously, dose unit of measure: mgs. * Maintenance: Mycophenolate mofetil (MMF) administered by mouth twice daily, dose unit of measure: mgs. * Maintenance: Beginning the day after methylprednisolone is completed, prednisone will be administered by mouth daily, dose unit of measure: mgs.

Biological: Lulizumab; Biological: Thymoglobulin®; Drug: Methylprednisolone; Drug: Mycophenolate Mofetil; Drug: Prednisone

Tacrolimus + SOC

ACTIVE COMPARATOR

N=27 participants will receive tacrolimus initiated according to local standard of care and adjusted over time (maintenance) to target optimal trough levels measured in ng/mL: 0 to 6 months, 7 to 12 months and, thereafter, until completion of study participation. Dose unit of measure: mg/kg. Plus (+) Standard of Care (SOC) Regimen, per protocol- Renal transplant recipients will receive FDA-approved, immunosuppressive medications according to standard of care at Emory Transplant Center: * Induction Thymoglobulin: Administered intravenously, dose unit of measure: mgs. * Induction Methylprednisolone: Administered intravenously, dose unit of measure: mgs. * Maintenance: Mycophenolate mofetil (MMF) administered by mouth twice daily, dose unit of measure: mgs. * Maintenance: Beginning the day after methylprednisolone is completed, prednisone will be administered by mouth daily, dose unit of measure: mgs.

Drug: Tacrolimus; Biological: Thymoglobulin®; Drug: Methylprednisolone; Drug: Mycophenolate Mofetil; Drug: Prednisone

Interventions

Lulizumab BIOLOGICAL

Lulizumab is a pegylated, humanized monovalent domain antibody construct that is specific for human cluster of differentiation CD28.

Also known as: BMS-931699, anti-CD28 domain antibody (anti-CD28 dAb)

Lulizumab + SOC

Tacrolimus DRUG

Standard of Care: Renal transplant rejection prophylaxis.

Also known as: Prograf®

Tacrolimus + SOC

Thymoglobulin® BIOLOGICAL

Standard of Care: Renal transplant rejection prophylaxis.

Also known as: antithymocyte globulin

Lulizumab + SOC; Tacrolimus + SOC

Methylprednisolone DRUG

Standard of Care: Renal transplant rejection prophylaxis.

Also known as: corticosteroid

Lulizumab + SOC; Tacrolimus + SOC

Mycophenolate Mofetil DRUG

Standard of Care: Renal transplant rejection prophylaxis.

Also known as: MMF, CellCept®

Lulizumab + SOC; Tacrolimus + SOC

Prednisone DRUG

Standard of Care: Renal transplant rejection prophylaxis.

Also known as: corticosteroid

Lulizumab + SOC; Tacrolimus + SOC

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Individuals who meet all of the following criteria are eligible for enrollment as study participants:
• Must be able to understand and provide informed consent;
• Negative crossmatch (actual or virtual) or a Panel Reactive Antibody (PRA) of 0% on historic and admission sera;
• First time renal transplant from either a living or deceased donor;
• Deceased donor recipients only: Deceased donor kidneys with Kidney Donor Profile Indices (KDPI) \<85%;
• Female study participants of childbearing potential must have a negative pregnancy test prior to randomization;
• Agreement to use contraception; according to the Food and Drug Administration (FDA) Office of Women's Health (http://www.fda.gov/birthcontrol), there are a number of birth control methods that are more than 80 percent effective.
• Female study participants of child-bearing potential and male study participants must consult with their physician and determine the most suitable method(s) from this list to be used from the time that study treatment begins until after study completion;
• Study participants must have a negative purified protein derivative (PPD) or negative testing for tuberculosis using an approved interferon-gamma release assay (IGRA) blood test, such as:
• QuantiFERON®-TB Gold In-Tube test (QFT-GIT) or
• TSPOT® TB test ---PPD or IGRA testing must be documented to have been performed within 52 weeks before transplant;
• Documented completion of varicella vaccination series ≥ 8 weeks prior to enrollment, OR verification of a history of varicella or zoster by a physician OR positive laboratory confirmation of varicella immunity or disease; and,
• Immunizations are up-to-date based on the CDC° adult vaccination recommendations:
• https://www.cdc.gov/vaccines/schedules/hcp/imz/adult.html
• °Centers for Disease Control and Prevention (CDC)

You may not qualify if:

• Individuals who meet any of these criteria are not eligible for enrollment as study participants:
• Inability or unwillingness of a study participant to give written informed consent or comply with study protocol;
• Recipient of previous organ transplant of any type;
• Need for multi-organ transplant;
• Calculated panel reactive antibody (cPRA) or panel reactive antibody (PRA) \>20% at any time prior to enrollment;
• Known hypersensitivity to mycophenolate mofetil (MMF) or any of the drug's components;
• Human immunodeficiency virus (HIV): individuals known to be HIV positive;
• Known history of Bacillus Calmette-Guérin (BCG) vaccination;
• Individuals at significant risk of early recurrence of the primary renal disease including: -Focal Segmental Glomerulosclerosis (FSGS)
• Membranoproliferative Glomerulonephropathy (MPGN) type 2
• Hemolytic Uremia Syndrome/Thrombotic thrombocytopenic purpura (HUS/TTP), or
• any other disease that, in the opinion of the investigator, is at increased likelihood of recurrence and which may result in rapid decline in renal function
• Known history of high-risk thrombotic events or risk factors; including any of the following:
• Factor V Leiden, elevated homocysteine, positive lupus anticoagulant, elevated anticardiolipin antibody, heparin induced thrombocytopenia
• A family history of a heritable thrombotic condition

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Bristol-Myers Squibb: collaborator
• PPD Development, LP: collaborator

Study Sites (1)

Emory University Hospital

Atlanta, Georgia, 30332, United States

Location

Related Links

• National Institute of Allergy and Infectious Diseases (NIAID)
• Division of Allergy, Immunology, and Transplantation (DAIT)

MeSH Terms

Conditions

Rejection, Psychology

Interventions

lulizumab pegol; Tacrolimus; thymoglobulin; Antilymphocyte Serum; Methylprednisolone; Adrenal Cortex Hormones; Mycophenolic Acid; Prednisone

Condition Hierarchy (Ancestors)

Social Behavior; Behavior

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals; Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Pregnadienediols

Study Officials

• Christian P. Larsen, MD, DPhil

  Emory Transplant Center, Emory University

  STUDY CHAIR

• Andrew B. Adams, MD, PhD

  Emory Transplant Center, Emory University

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: May 21, 2021
• First Posted: May 26, 2021
• Study Start: January 10, 2022
• Primary Completion: September 22, 2022
• Study Completion: September 22, 2022
• Last Updated: March 22, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will share
• Time Frame: On average, within 24 months after database lock for the trial.
• Access Criteria: Open access.

Locations

US (1)