Treg Modulation With CD28 and IL-6 Receptor Antagonists
Condition: Living-Donor Kidney Transplant; Kidney Transplant Recipients
Study type: Interventional
Phase: Phase 1/Phase 2

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.
    

Intervention name(s): lulizumab pegol; antithymocyte globulin (rabbit); methylprednisolone; tocilizumab; Prednisone; everolimus; belatacept; mycophenolate mofetil; mycophenolic acid
Intervention type(s): Biological; Biological; Drug; Biological; Drug; Drug; Biological; Drug; Drug
Intervention description(s): 25 mg subcutaneously (SC) on Day 1 post transplantation then 12.5 mg SC weekly through day 77 (Week 11); 1.5 mg/kg intravenously (IV) on Day 0 (day of transplantation) and the day following (Day 1); 500 mg (IV) on Day 0 (day of transplantation), 250 mg (IV) on Day 1 and 125 mg (IV) on Day 2; 8 mg/kg (IV) on Day 2 post transplantation followed by 162 mg (SC) every 2 weeks through day 168 (Week 24); 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; 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.; 5 mg/kg (IV) every 4 weeks starting on Day 84 (Week 12) and continuing through Day 364 (Week 52); An option for participants who do not tolerate everolimus: to be switched to either
mycophenolate mofetil 1000 mg administered orally twice daily or
mycophenolic acid; An option for participants who do not tolerate everolimus: to be switched to either
mycophenolic acid 720 mg taken orally twice daily or
mycophenolate mofetil
Other intervention name(s): BMS-931699; ATG (rabbit); Thymoglobulin®; Solu-Medrol ®; Actemra®; prednisone tablets; Rayos®; Zortress®; Nulojix®; MMF; CellCept®; Myfortic®
Intervention MeSH terms: Mycophenolic Acid; Prednisone; Methylprednisolone; Methylprednisolone Hemisuccinate; Everolimus; Abatacept; Thymoglobulin; Antilymphocyte Serum
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
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