Clinical Trials Directory

Trials / Completed

CompletedNCT04066114

Treg Modulation With CD28 and IL-6 Receptor Antagonists

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

Status
Completed
Phase
Phase 1 / Phase 2
Study type
Interventional
Enrollment
24 (actual)
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID) · NIH
Sex
All
Age
18 Years – 70 Years
Healthy volunteers
Not accepted

Summary

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

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.

Conditions

Interventions

TypeNameDescription
BIOLOGICALlulizumab pegol25 mg subcutaneously (SC) on Day 1 post transplantation then 12.5 mg SC weekly through day 77 (Week 11)
BIOLOGICALantithymocyte globulin (rabbit)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.
DRUGmethylprednisolone500 mg (IV) on Day 0 (day of transplantation), 250 mg (IV) on Day 1 and 125 mg (IV) on Day 2
BIOLOGICALtocilizumab8 mg/kg (IV) on Day 2 post transplantation followed by 162 mg (SC) every 2 weeks through day 168 (Week 24)
DRUGPrednisoneBeginning 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
DRUGeverolimusInitial 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.
BIOLOGICALbelatacept5 mg/kg (IV) every 4 weeks starting on Day 84 (Week 12) and continuing through Day 364 (Week 52)
DRUGmycophenolate mofetilmycophenolate 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.
DRUGmycophenolic acidmycophenolic 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.

Timeline

Start date
2019-12-11
Primary completion
2023-09-14
Completion
2023-09-14
First posted
2019-08-26
Last updated
2024-10-09
Results posted
2024-10-09

Locations

7 sites across 1 country: United States

Regulatory

Source: ClinicalTrials.gov record NCT04066114. Inclusion in this directory is not an endorsement.