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Living-Donor Kidney TransplantPhase 1/2NCT04066114

Treg Modulation With CD28 and IL-6 Receptor Antagonists

A Phase 1/2 study testing lulizumab pegol, antithymocyte globulin (rabbit) and methylprednisolone in people with Living-Donor Kidney Transplant and Kidney Transplant Recipients, run by National Institute of Allergy and Infectious Diseases (NIAID) at 7 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The purpose of this study is to evaluate the safety of using lulizumab pegol with tocilizumab, belatacept, and everolimus in kidney transplant recipients. Read more about this study

Who is it for?
Ages 18 to 70 years
What is being tested?
lulizumab pegol, antithymocyte globulin (rabbit) and methylprednisolone
Could I receive a placebo?
No, everyone receives an active treatment
How many people
24 participants
Where
7 sitesUnited States
Study dates
11 Dec 2019to 14 Sep 2023
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 the following criteria are eligible for enrollment as study participants:
  • Able to understand and provide informed consent
  • Agreement to use highly effective (<1% failure rate) methods of contraception: Women of Childbearing Potential (WOCBP)-
  • Progestogen only hormonal contraception associated with inhibition of ovulation,
  • Hormonal methods of contraception including oral contraceptive pills containing a combination of estrogen + progesterone, vagina ring, injectables, implants and intrauterine devices (IUDs),
  • Non-hormonal IUDs,
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  • Bilateral tubal occlusion,
  • Vasectomized partner,
  • Intrauterine hormone-releasing system (IUS), or
  • Complete abstinence.
  • Note: Female participants of childbearing potential must consult with their physician and determine the most suitable method(s) from this list to be used for 12 months while on study drug regimen.
  • Male Participants-
  • --Must use a latex or other synthetic condom during any sexual activity with WOCBP until one month after the last dose of lulizumab (e.g., up to 3.5 months in duration).
  • Recipient of primary, nonhuman leukocyte antigen identical living donor kidney transplant
  • No donor specific antibodies prior to transplant that are considered to be of clinical significance by the site investigator
  • Epstein-Barr virus (EBV) positive serology
  • Cytomegalovirus (CMV) positive serology, unless donor-recipient pair are both CMV negative
  • Negative testing for latent Tuberculosis (TB) infection within 3 months prior to transplant
  • Testing should be conducted using either a purified protein derivative (PPD) or an interferon-gamma release assay blood test for TB (i.e. QuantiFERON®-TB Gold in-Tube test or T-SPOT® TB test)
  • Subjects with a positive test for latent TB infection must complete appropriate therapy for Latent tuberculosis infection (LTBI). ---A subject is considered eligible only if they have a negative test for LTBI within 3 months prior to transplant or, they have appropriately completed LTBI therapy prior to transplant.
  • Note: Latent TB infection treatment regimens should be among those endorsed by the CDC (Division of TB Elimination, 2016).
  • In the absence of contraindication, vaccinations must be up to date for hepatitis B, influenza, pneumococcal, varicella and herpes zoster, and measles, mumps, and rubella (MMR)
  • Hepatitis C Virus (HCV) antibody positive subjects with negative HCV by PCR testing are eligible if they:
  • have spontaneously cleared infection, or
  • are in sustained virologic remission for at least 12 weeks after treatment for HCV.
  • Negative SARS-CoV-2 PCR test result performed within 2 weeks of transplant (SARS-CoV-2 is the virus that causes COVID-19)

Who cannot join

  • Individuals who meet any of these criteria are not eligible for enrollment as study participants-
  • Prisoners or subjects who are compulsorily detained
  • Inability or unwillingness of a participant to give written informed consent or comply with study protocol
  • Candidate for a multiple solid organ or tissue transplants
  • Prior history of organ or cellular transplantation
  • Known to have idiopathic focal segmental glomerulosclerosis (FSGS) as the underlying cause of kidney failure (ESRD)
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  • Requirement for uninterrupted anticoagulation therapy, including Plavix.
  • Known hypersensitivity to mechanistic target of rapamycin (mTOR) inhibitors or contraindication to everolimus (including history of wound healing complications)
  • History of severe allergic and/or anaphylactic reactions to humanized or murine monoclonal antibodies
  • Hypersensitivity to rabbit proteins or rabbit anti-thymocyte Globulin (ATG)
  • Known hypersensitivity to ACTEMRA® (tocilizumab) or lulizumab pegol (BMS-931699)
  • The human immunodeficiency virus (HIV) infected subjects, including those who are well controlled on antiretrovirals
  • Positive hepatitis B surface antigen (HBSAg), or hepatitis B core antibody (HBcAB) serology
  • Hepatitis C virus antibody positive (HCV Ab+) subjects who have failed to demonstrate sustained viral remission for more than 12 weeks after anti-viral treatment
  • Subjects with a previous history of active Tuberculosis (TB)
  • Known active current viral, fungal, mycobacterial or other infections (including, but not limited to tuberculosis and atypical mycobacterial disease, Hepatitis B and C, and herpes zoster)
  • Donor or recipient residing in areas where the annual incidence ≥ 21 cases per 100,000) for coccidioidomycosis according to current CDC map: (https://www.cdc.gov/fungal/diseases/coccidioidomycosis/causes.html)
  • Donors or recipients residing in low risk zones (annual <21 cases per 100,000) will not require additional screening
  • History of malignancy except treated basal cell cancer of the skin
  • History of hemolytic-uremic syndrome/ thrombotic thrombocytopenia purpura
  • History of demyelinating disorders (e.g., multiple sclerosis, chronic inflammation demyelinating polyneuropathy)
  • History of gastrointestinal perforations, active inflammatory bowel disease or diverticulitis
  • Any previous treatment with alkylating agents such as chlorambucil, or with total lymphoid irradiation
  • Receipt of a live vaccine within 30 days prior to transplantation.
  • 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 participant's ability to comply with study requirements, or
  • that may impact the quality or interpretation of the data obtained from the study
  • Severe hyperlipidemia (defined by total cholesterol >350 mg/dL, LDL >190 mg/dL, or triglycerides >500 mg/dL)
  • Transaminase levels elevated more than 1.5 times the upper limit of normal (ULN) within 7 days prior to enrollment
  • The absolute neutrophil count (ANC) < 2,000 per mm^3 within 7 days prior to enrollment
  • Platelet count less than 100,000 per mm^3 within 7 days prior to enrollment
  • More than 50% CD8+/ CD28- T-cells in peripheral blood
  • A calculated panel reactive antibody (cPRA) ≥20%, as determined by each participating site's laboratory
  • Positive pregnancy test in women of child bearing potential, currently breastfeeding, or planning to become pregnant during the timeframe of the study or follow-up period
  • Participation in any other studies with investigational drugs or regimens in the preceding year

Trial locations and contacts

7 sites in 1 country.

7 sites in 1 country

United States7 sites

  • University of Colorado (UC) Health Transplant Center - Anschutz

    Aurora, Colorado, 80045

  • University of Alabama School of Medicine: Transplantation

    Birmingham, Alabama, 35233

  • Northwestern Memorial Hospital: Transplantation

    Chicago, Illinois, 60611

  • Cleveland Clinic Foundation: Transplantation

    Cleveland, Ohio, 44195

  • Duke University Medical Center: Transplantation

    Durham, North Carolina, 27710

  • University of Nebraska Medical Center: Transplantation

    Omaha, Nebraska, 68105

  • University of California San Francisco School of Medicine: Transplantation

    San Francisco, California, 94143

Other trials in United States

About this study

Official title: Regulatory T Cell Modulation in Kidney Transplantation With Biologic Blockade of Dual Effector Pathways, CD28 and IL-6 (CTOT-24)

The purpose of this study is to evaluate the safety of using lulizumab pegol with tocilizumab, belatacept, and everolimus in kidney transplant recipients.

Read the detailed description

This research study is for adults who are planning to have a kidney transplant from a living donor.

In Brief:

Those who have a transplant take immunosuppressive therapy to prevent the body from rejecting the transplanted organ. Rejection occurs when the body's defense system (immune cells) recognizes the transplant as a foreign object. These immune cells and the substances they produce can damage the transplanted kidney. It is important to prevent rejection episodes, so the kidney transplant lasts as long as possible.

Most transplant doctors in the United States give a combination of two or three drugs to prevent rejection. People with a transplant must take these drugs every day. Although kidney transplant recipients usually do well in the first five years after transplant, researchers want to find new ways to prevent rejection and avoid the side effects that the current drugs can cause.

This study will test a new combination of four drugs to evaluate whether this combination is safe for kidney transplant recipients:

  • lulizumab pegol (BMS-931699)
  • tocilizumab
  • belatacept and
  • everolimus.

Belatacept and everolimus are already approved for use as anti-rejection drugs in kidney transplant recipients. Lulizumab pegol and tocilizumab act on specific molecules (specifically CD28 and interleukin 6, respectively) on immune cells: these actions are different from how the older rejection drugs work.

Summary: This is a prospective multicenter open-label clinical trial of 10 living donor kidney transplant recipients. Safety of lulizumab pegol (BMS-931699) in the context of a novel immunosuppressive regimen (anti-thymocyte globulin (rabbit) (ATG), steroids,) Nulojix® (belatacept), Actemra® (tocilizumab), and Zortress®(everolimus)) will be assessed. Study participation involves a minimum of one year of follow-up post-transplant.

  • IMPORTANT NOTICE: * The National Institute of Allergy and Infectious Diseases and the Clinical Trials in Organ Transplantation (CTOT) do not recommend the discontinuation of immunosuppressive therapy for recipients of cell, organ, or tissue transplants outside of physician-directed, controlled clinical studies. Discontinuation of prescribed immunosuppressive therapy can result in serious health consequences and should only be performed in certain rare circumstances, upon the recommendation and with the guidance of your health care provider.
Being tested
lulizumab pegol, antithymocyte globulin (rabbit), methylprednisolone, tocilizumab, Prednisone
Keywords
adult living-donor kidney transplant recipients, novel immunosuppressive (IS) therapy regimen, lulizumab pegol (BMS-931699), CD28 and IL-6 biologic blockade, CD28 and IL-6 receptor antagonists, T regulatory cells (Treg) modulation

What participants receive

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

  • lulizumab pegolBiological

    Also called BMS-931699

    25 mg subcutaneously (SC) on Day 1 post transplantation then 12.5 mg SC weekly through day 77 (Week 11)

  • antithymocyte globulin (rabbit)Biological

    Also called ATG (rabbit), Thymoglobulin®

    Study participants are administered four doses of rabbit anti-thymocyte globulin, total dose 6 mg/kg given in divided doses on the day of transplantation and days 1-3.

  • methylprednisoloneDrug

    Also called Solu-Medrol ®

    500 mg (IV) on Day 0 (day of transplantation), 250 mg (IV) on Day 1 and 125 mg (IV) on Day 2

  • tocilizumabBiological

    Also called Actemra®

    8 mg/kg (IV) on Day 2 post transplantation followed by 162 mg (SC) every 2 weeks through day 168 (Week 24)

  • PrednisoneDrug

    Also called prednisone tablets, Rayos®

    Beginning on Day 3 post transplantation, taken orally: 60 mg daily

    • Days 4 through 10: 30 mg daily
    • Days 11 through 17: 20 mg daily
    • Days 18 through 24: 10 mg daily
    • After Day 24: continued taper of dose to final maintenance dose of 5 mg, per protocol

  • everolimusDrug

    Also called Zortress®

    Initial dose of 0.75 mg taken orally twice daily on Day 14 days after transplantation. Dose will be titrated to target trough levels 3-8 ng/mL.

  • belataceptBiological

    Also called Nulojix®

    5 mg/kg (IV) every 4 weeks starting on Day 84 (Week 12) and continuing through Day 364 (Week 52)

  • mycophenolate mofetilDrug

    Also called MMF, CellCept®

    mycophenolate mofetil is started no later than one day after transplant at 1000mg PO twice daily provided WBC count permits, staying on it until everoliumus level is within therapeutic range. Participants that do no tolerate everolimus can stay on or switch back to mycophenolate mofetil 1000 mg twice daily and remain in trial.

  • mycophenolic acidDrug

    Also called Myfortic®

    mycophenolic acid is started no later than one day after transplant at 720mg PO twice daily provided WBC count permits, staying on it until everoliumus level is within therapeutic range. Participants that do not tolerate everolimus can stay on or switch back to 720 mg twice daily of mycophenolic acid and remain in trial.

Study groups in NCT04066114
Study groupRoleWhat they receive
lulizumab pegol + novel ISRExperimentallulizumab pegol + novel ISR: lulizumab pegol plus immunosuppressive regimen (anti-thymocyte globulin (rabbit), steroids,) belatacept, tocilizumab, and everolimus)
Receives: Biological: lulizumab pegol; Biological: antithymocyte globulin (rabbit); Drug: methylprednisolone; Biological: tocilizumab; Drug: Prednisone; Drug: everolimus; Biological: belatacept; Drug: mycophenolate mofetil; Drug: mycophenolic acid

What is being measured

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

  1. The Proportion of Participants Who Remain Free of Biopsy-proven Acute T-cell Mediated or Antibody-mediated Rejection (as Defined by Banff Criteria) at 6 Months Post-transplantation.

    Acute T-cell mediated rejection was defined using the Banff 2007 criteria. Participants with a Banff grade of greater than or equal to 1A were determined to have met the endpoint. Severity is graded as 1A, 1B, 2A, 2B, or 3, with 1A being the mildest form of cellular rejection and 3 being the most severe form of cellular rejection. Antibody mediated rejection was defined as diffusely positive staining for C4d, presence of circulating anti-donor antibodies, and morphologic evidence of acute tissue injury. Clinical rejection occurring prior to 6 months, defined as treated rejection without biopsy confirmation was included as acute rejection with respect to the endpoint.

    Measured: 6 months post-transplantation

Secondary outcomes (1)

  1. The Proportion of Participants Who Remain Free of Biopsy-proven Acute T-cell Mediated or Antibody-mediated Rejection (as Defined by Banff Criteria) at 12 Months Post-transplantation.

    Acute T-cell mediated rejection was defined using the Banff 2007 criteria. Participants with a Banff grade of greater than or equal to 1A were determined to have met the endpoint. Severity is graded as 1A, 1B, 2A, 2B, or 3, with 1A being the mildest form of cellular rejection and 3 being the most severe form of cellular rejection. Antibody mediated rejection was defined as diffusely positive staining for C4d, presence of circulating anti-donor antibodies, and morphologic evidence of acute tissue injury. Clinical rejection occurring prior to 12 months, defined as treated rejection without biopsy confirmation were included as acute rejection with respect to the endpoint.

    Measured: 12 months 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 Aug 2019
  2. Study start11 Dec 2019
  3. Primary completion14 Sep 2023
  4. Study completion14 Sep 2023

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
24 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04066114
Sponsor's protocol ID
DAIT CTOT-24
Other IDs
NIAID CRMS ID#: 38581
Status last verified
Sep 2026
First submitted
21 Aug 2019
Last updated
24 Sep 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Chandran S, Tang Q, Leung JC, Armstrong BD, Friedewald JJ, Kirk AD, Laszik ZG, Goldstein J, Morsheimer M, Vincenti FG. Regulatory T cell modulation with selective CD28 blockade and IL-6 receptor antagonist in kidney transplant recipients: Results of CTOT-24-a prospective clinical trial. Am J Transplant. 2026 Jul 22:S1600-6135(26)02676-6. doi: 10.1016/j.ajt.2026.07.016. Online ahead of print.

    PubMed 42486389

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing lulizumab pegol, antithymocyte globulin (rabbit) and methylprednisolone in people with Living-Donor Kidney Transplant and Kidney Transplant Recipients, run by National Institute of Allergy and Infectious Diseases (NIAID) at 7 sites 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 26 inclusion and 36 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: finished, as of the sponsor's last update on 24 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites 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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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?

Yes. Results are posted in the registry (first posted 9 Oct 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

The Proportion of Participants Who Remain Free of Biopsy-proven Acute T-cell Mediated or Antibody-mediated Rejection (as Defined by Banff Criteria) at 6 Months Post-transplantation. (time frame: 6 months 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 NCT04066114, which also lists 1 linked publication.

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 24 Sep 2026.

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