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Kidney TransplantationPhase 2NCT04903054

Selective CD28 Blockade in Renal Transplant Recipients

A Phase 2 study testing Lulizumab, Tacrolimus and Thymoglobulin® in people with Kidney Transplantation and Renal Transplant Recipients, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 70 years
What is being tested?
Lulizumab, Tacrolimus and Thymoglobulin®
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
1 siteUnited States
Study dates
10 Jan 2022to 22 Sep 2022
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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;
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  • 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)

Who cannot join

  • 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;
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  • 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
  • Recurrent Deep vein thrombosis (DVT) or Pulmonary Embolism (PE), or
  • Unexplained stillborn infant or recurrent spontaneous abortion of other congenital or acquired thrombotic disorder
  • History of malignancy within 5 years of enrollment or any history of hematogenous malignancy or lymphoma.
  • --Note: Study participants with curatively treated non-melanomatous skin cancer or curatively treated cervical carcinoma in situ may be enrolled;
  • Study participants who are on biologic treatments for autoimmune disease;
  • Study participants who are involuntarily detained (e.g. prison, jail, compulsory psychiatric or medical therapy);
  • Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator:
  • May pose additional risks from participation in the study,
  • May interfere with the study participant's ability to comply with study requirements, or
  • May impact the quality or interpretation of the data obtained from the study;
  • Human leukocyte antigen (HLA) identical donor/recipient pairing;
  • Use of investigational drugs within 4 weeks of transplant;
  • Study participants who are NOT Epstein-Barr virus (EBV) seropositive
  • -A prior documented EBV seropositive result at enrollment does not need to be repeated --For this study, EBV seropositive patients are defined as having evidence of acquired immunity shown by the presence of immunoglobulin G (IgG) antibodies to viral capsid antigen (VCA) and the presence of antibodies to EBV nuclear antigen (EBNA or EBNA1);
  • Hepatitis C virus (HCV): Study participants who are HCV RNA PCR positive at prerandomization re-evaluation
  • -Study participants who are seropositive must have 2 consecutive negative HCV RNA PCR at least 24 weeks apart;
  • Hepatitis B virus: Individuals with any of the following are NOT eligible:
  • Recipient or donor positive for hepatitis B surface antigen (HBsAg)
  • Recipient or donor with antibodies to hepatitis B core antigen (anti-HBc)
  • Recipient or donor with HBV DNA detectable by PCR;
  • Recipient of a live or live-attenuated vaccine within 8 weeks prior to transplant;
  • Cytomegalovirus (CMV) seronegative individuals accepting an organ from a CMV seropositive donor;
  • Study participants undergoing transplant using:
  • Organs from donation after circulatory death (DCD) donor
  • Donor with Kidney Donor Profile Index (KDPI) >85%, or
  • Anticipated cold ischemia time >28 hours; or,
  • ABO incompatible donor kidney.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Emory University Hospital

    Atlanta, Georgia, 30332

Other trials in United States

About this study

Official title: Selective CD28 Blockade With Lulizumab Compared to CNI Inhibition With Tacrolimus in Renal Transplant Recipients

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.

Read the detailed description

This is a phase 2a, open-label, prospective, randomized (1:1), controlled, single center study evaluating the safety and efficacy of lulizumab (a CD28 specific domain antibody [CD28dAb]) compared to tacrolimus as the primary immunosuppressant in first-time renal transplant recipients. The study will take place at Emory University Hospital in Atlanta, Georgia, United States (US).

There are two arms/groups in this study, the Control (tacrolimus) group and the Investigational (lulizumab) group. The two arms will be assigned to treatment regimens for the first 12 months after transplantation; at that point, all participants in each arm will be transitioned to a physician directed Standard of Care (SOC) immunosuppressive regimen, and all participants will be assessed at 15 months after transplantation.

All participants will receive induction therapy with Thymoglobulin and Methylprednisolone and maintenance therapy with Mycophenolate Mofetil (MMF) and Prednisone.

Being tested
Lulizumab, Tacrolimus, Thymoglobulin®, Methylprednisolone, Mycophenolate Mofetil
Keywords
CD28 blockade, Cluster of Differentiation (CD), CNI inhibition, immune modulation, rejection
Medical subject headings
Rejection, Psychology

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LulizumabBiological

    Also called BMS-931699, anti-CD28 domain antibody (anti-CD28 dAb)

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

  • TacrolimusDrug

    Also called Prograf®

    Standard of Care: Renal transplant rejection prophylaxis.

  • Thymoglobulin®Biological

    Also called antithymocyte globulin

    Standard of Care: Renal transplant rejection prophylaxis.

  • MethylprednisoloneDrug

    Also called corticosteroid

    Standard of Care: Renal transplant rejection prophylaxis.

  • Mycophenolate MofetilDrug

    Also called MMF, CellCept®

    Standard of Care: Renal transplant rejection prophylaxis.

  • PrednisoneDrug

    Also called corticosteroid

    Standard of Care: Renal transplant rejection prophylaxis.

Study groups in NCT04903054
Study groupRoleWhat they receive
Lulizumab + SOCExperimentalN=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.
Receives: Biological: Lulizumab; Biological: Thymoglobulin®; Drug: Methylprednisolone; Drug: Mycophenolate Mofetil; Drug: Prednisone
Tacrolimus + SOCActive comparatorN=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.
Receives: Drug: Tacrolimus; Biological: Thymoglobulin®; Drug: Methylprednisolone; Drug: Mycophenolate Mofetil; Drug: Prednisone

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: From Month 2 to Month 12 Post Transplantation

Secondary outcomes (24)

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

    Safety measure. Defined by Banff 2017 kidney criteria.

    Reference: Haas, M. et al. The Banff 2017 Kidney Meeting Report: Revised diagnostic criteria for chronic active T cell-mediated rejection, antibody-mediated rejection, and prospects for integrative endpoints for next-generation clinical trials. Am J Transplant. 18(2):293-307.

    Measured: Up to 15 Months Post Transplantation

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

    Safety measure. Defined by Banff 2017 kidney criteria.

    Reference: Haas, M. et al. The Banff 2017 Kidney Meeting Report: Revised diagnostic criteria for chronic active T cell-mediated rejection, antibody-mediated rejection, and prospects for integrative endpoints for next-generation clinical trials. Am J Transplant. 18(2):293-307.

    Measured: Up to 15 Months Post Transplantation

  3. Cumulative Incidence of Serious Adverse Events

    Safety measure.

    Measured: Up to 15 Months Post Transplantation

  4. Incidence of Serious Infection(s) of Special Interest

    Safety measure. Definition: The occurrence of infection(s) requiring participant hospitalization or prolonged therapy, including but not limited to treatment ≥20 days.

    Measured: Up to 15 Months Post Transplantation

  5. Incidence of Cytomegalovirus (CMV) Viremia

    Safety measure.

    Measured: Up to 15 Months Post Transplantation

  6. Incidence of BK Polyoma Virus (BKV) Viremia

    Safety measure.

    Measured: Up to 15 Months Post Transplantation

  7. Incidence of Any Malignancy, Including but Not Limited to PTLD

    Safety measure.

    Definitions:

    • Malignancy: A term for diseases in which abnormal cells divide without control and can invade nearby tissues.
    • Post-transplant Lymphoproliferative Disorder (PTLD) : A rare but well-known complication of solid organ transplants and hematopoietic stem cell transplantation.

    Measured: Up to 15 Months Post Transplantation

  8. Proportion of Participants Experiencing the Composite Outcome of Death or Allograft Failure

    Efficacy measure.

    Measured: Up to 15 Months Post Transplantation

  9. Proportion of Participants with Biopsy Proven Acute T-cell Mediated Cellular Rejection (BPaTCMR)

    Efficacy measure.

    Defined by Banff 2017 kidney criteria.

    Reference: Haas, M. et al. The Banff 2017 Kidney Meeting Report: Revised diagnostic criteria for chronic active T cell-mediated rejection, antibody-mediated rejection, and prospects for integrative endpoints for next-generation clinical trials. Am J Transplant. 18(2):293-307.

    Measured: Up to 15 Months Post Transplantation

  10. Proportion of Participants Treated for Kidney Transplant Rejection

    Efficacy measure. Definition: Participant requiring treatment for rejection with corticosteroids, T-cell depleting therapy, and/or any other treatment for kidney transplant rejection.

    Measured: Up to 15 Months Post Transplantation

  11. Proportion of Participants Treated for Acute Rejection Due to Clinical Suspicion

    Efficacy measure. Acute rejection due to a clinical suspicion rather than BPaTCMR or BP-aABMR.

    Definitions:

    • BPaTCMR: Biopsy proven acute T-cell mediated cellular rejection
    • BP-aABMR: Biopsy proven active antibody mediated rejection

    Measured: Up to 15 Months Post Transplantation

  12. Proportion of Participants with Biopsy Proven Active Antibody Mediated Rejection (BP-aABMR)

    Efficacy measure. Defined by Banff 2017 kidney criteria.

    Reference: Haas, M. et al. The Banff 2017 Kidney Meeting Report: Revised diagnostic criteria for chronic active T cell-mediated rejection, antibody-mediated rejection, and prospects for integrative endpoints for next-generation clinical trials. Am J Transplant. 18(2):293-307.

    Measured: Up to 15 Months Post Transplantation

  13. Proportion of Participants with aTCMR Changes in Allograft Biopsies

    Efficacy measure.

    Definitions:

    • aTCMR:acute T-cell mediated cellular rejection
    • Defined by Banff 2017 kidney criteria.

    Reference: Haas, M. et al. The Banff 2017 Kidney Meeting Report: Revised diagnostic criteria for chronic active T cell-mediated rejection, antibody-mediated rejection, and prospects for integrative endpoints for next-generation clinical trials. Am J Transplant. 18(2):293-307.

    Measured: Up to 15 Months Post Transplantation

  14. Time to Event for aTCMR Changes in Allograft Biopsies

    Efficacy measure.

    Definitions:

    • aTCMR:acute T-cell mediated cellular rejection
    • Defined by Banff 2017 kidney criteria.

    Reference: Haas, M. et al. The Banff 2017 Kidney Meeting Report: Revised diagnostic criteria for chronic active T cell-mediated rejection, antibody-mediated rejection, and prospects for integrative endpoints for next-generation clinical trials. Am J Transplant. 18(2):293-307.

    Measured: Up to 15 Months Post Transplantation

  15. Proportion of Participant Who Develop De-Novo Donor Specific Antibody

    Efficacy measure.

    Measured: Up to 15 Months Post Transplantation

  16. Change in Estimated Glomerular Filtration Rate (eGFR)

    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.

    Measured: From Month 2 to Month 15 Post Transplantation

  17. Proportion of Participants with Delayed Graft Function

    Efficacy measure.

    Measured: Within 1 Month Post Transplantation

  18. Hemoglobin A1C

    Efficacy measure. Definition: HbA1c: Glycosylated hemoglobin, a measure of the average plasma concentration of blood sugar (glucose) over the previous three months.

    Measured: Month 12 Post Transplantation

  19. Days to Event: TCMR

    Efficacy measure. TCMR: T-cell mediated rejection.

    Measured: Up to 15 Months Post Transplantation

  20. Days to Event: Antibody mediated rejection (ABMR)

    Efficacy measure. ABMR: Antibody mediated rejection.

    Measured: Up to 15 Months Post Transplantation

  21. Days to Event: De-Novo Donor Specific Antibody (DSA) Formation

    Efficacy measure.

    Measured: Up to 15 Months Post Transplantation

  22. Days to Event: Graft Loss

    Efficacy measure.

    Measured: Up to 15 Months Post Transplantation

  23. Standardized Blood Pressure

    Efficacy measure.

    Measured: Month 12 and Month 15 Post Transplantation

  24. Fasting Lipid Profile

    Efficacy measure. Included: Total cholesterol, LDL, HDL, and triglyceride.

    Measured: Month 12 and Month 15 Post Transplantation

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 May 2021
  2. Study start10 Jan 2022
  3. Primary completion22 Sep 2022
  4. Study completion22 Sep 2022

Why it stopped: Limited period of availability of a supply of the study drug and difficulties in enrollment

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04903054
Sponsor's protocol ID
DAIT RTB-011
Other IDs
U01AI138909, NIAID CRMS ID#: 38687
Status last verified
Mar 2023
First submitted
21 May 2021
Last updated
22 Mar 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: The plan is to share data upon completion of the study in: Immunology Database and Analysis Portal (ImmPort), a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Lulizumab, Tacrolimus and Thymoglobulin® in people with Kidney Transplantation and Renal Transplant Recipients, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 42 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 22 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Mean Estimated Glomerular Filtration rate (eGFR) (MDRD) (time frame: From Month 2 to Month 12 Post Transplantation). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04903054.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Mar 2023.

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