Open-Label Phase 2 Trial of a Steroid-Free, CNI-Free, Belatacept-Based Immunosuppressive Regimen
NCT ID: NCT01856257
Last Updated: 2020-12-17
Study Results
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View full resultsBasic Information
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TERMINATED
PHASE2
71 participants
INTERVENTIONAL
2013-07-31
2016-04-30
Brief Summary
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Detailed Description
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The purpose of this study is to determine if NULOJIX® (belatacept), will minimize serious long term side effects seen with anti-rejection medications while still protecting the transplanted kidney from damage. The researchers also want to learn more about the safety of this treatment and the long term health of the transplanted kidney.
Conditions
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Keywords
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Thymoglobulin®+tacrolimus+MMF
Induction with Thymoglobulin®, methylprednisolone, and maintenance immunosuppression with tacrolimus and mycophenolate mofetil (MMF)
Anti-thymocyte Globulin (Rabbit)
The target dosage is 6mg/kg total over 3 to 4 days. The recommended route of administration is intravenous infusion using a high-flow vein.
methylprednisolone
Methylprednisolone will be administered at a target dose of 500 mg beginning on the day of transplant, and tapered to 250 mg day 1 post-transplant, 125 mg day 2 post-transplant, 60 mg day 3 post-transplant, 30 mg day 4 post-transplant and day 5 post-transplant 0 mg if therapeutic tacrolimus level achieved for groups 1 and 3.
mycophenolate mofetil
Mycophenolate Mofetil will be administered at a target dose of 1000 mg orally twice a day. Myfortic® (mycophenolate sodium) may be used as a replacement for MMF. Mycophenolate sodium will be dosed at 720 mg PO BID. Mycophenolate sodium will be adjusted based on clinical complications.
tacrolimus
The site investigator will identify a starting tacrolimus dose at their discretion, in order to achieve the target trough levels, no later than 5 days post-transplantation. The dose will be adjusted to 5-8ng/ml for the active comparator arm (thymoglobulin + tacrolimus + MMF arm) or tapered off in the experimental arm (basiliximab + 20 weeks of tacrolimus + MMF + belatacept).
Thymoglobulin®+belatacept+MMF
Induction with Thymoglobulin®, methylprednisolone, and maintenance with belatacept and mycophenolate mofetil (MMF)
Anti-thymocyte Globulin (Rabbit)
The target dosage is 6mg/kg total over 3 to 4 days. The recommended route of administration is intravenous infusion using a high-flow vein.
belatacept
Participants will receive belatacept at a dose of 10mg/kg up on day 1, 5, 14, 28, 56 and 84. After 84 days, subjects will receive a maintenance dose of 5 mg/kg every 4 weeks until completion of the trial.
methylprednisolone
Methylprednisolone will be administered at a target dose of 500 mg beginning on the day of transplant, and tapered to 250 mg day 1 post-transplant, 125 mg day 2 post-transplant, 60 mg day 3 post-transplant, 30 mg day 4 post-transplant and day 5 post-transplant 0 mg if therapeutic tacrolimus level achieved for groups 1 and 3.
mycophenolate mofetil
Mycophenolate Mofetil will be administered at a target dose of 1000 mg orally twice a day. Myfortic® (mycophenolate sodium) may be used as a replacement for MMF. Mycophenolate sodium will be dosed at 720 mg PO BID. Mycophenolate sodium will be adjusted based on clinical complications.
Basiliximab+20 weeks of tacrolimus+MMF + belatacept
Induction basiliximab and methylprednisolone, administration of NULOJIX® (belatacept) 24 hours post reperfusion (+/-12 hrs); maintenance immunosuppression with 1. )20 week course of Prograf® (tacrolimus) or equivalent 2.) CellCept® (mycophenolate mofetil- MMF), or Myfortic® (mycophenolate sodium), or equivalent.
Subjects participating in this arm may have tacrolimus reinstated, at a dose to be determined by the site investigator, if any of the following events occur: 1 - An acute rejection episode 2- Request of the subject or site Investigator.
belatacept
Participants will receive belatacept at a dose of 10mg/kg up on day 1, 5, 14, 28, 56 and 84. After 84 days, subjects will receive a maintenance dose of 5 mg/kg every 4 weeks until completion of the trial.
methylprednisolone
Methylprednisolone will be administered at a target dose of 500 mg beginning on the day of transplant, and tapered to 250 mg day 1 post-transplant, 125 mg day 2 post-transplant, 60 mg day 3 post-transplant, 30 mg day 4 post-transplant and day 5 post-transplant 0 mg if therapeutic tacrolimus level achieved for groups 1 and 3.
basiliximab
Basiliximab will be administered in two doses of 20 mg each.
mycophenolate mofetil
Mycophenolate Mofetil will be administered at a target dose of 1000 mg orally twice a day. Myfortic® (mycophenolate sodium) may be used as a replacement for MMF. Mycophenolate sodium will be dosed at 720 mg PO BID. Mycophenolate sodium will be adjusted based on clinical complications.
tacrolimus
The site investigator will identify a starting tacrolimus dose at their discretion, in order to achieve the target trough levels, no later than 5 days post-transplantation. The dose will be adjusted to 5-8ng/ml for the active comparator arm (thymoglobulin + tacrolimus + MMF arm) or tapered off in the experimental arm (basiliximab + 20 weeks of tacrolimus + MMF + belatacept).
Interventions
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Anti-thymocyte Globulin (Rabbit)
The target dosage is 6mg/kg total over 3 to 4 days. The recommended route of administration is intravenous infusion using a high-flow vein.
belatacept
Participants will receive belatacept at a dose of 10mg/kg up on day 1, 5, 14, 28, 56 and 84. After 84 days, subjects will receive a maintenance dose of 5 mg/kg every 4 weeks until completion of the trial.
methylprednisolone
Methylprednisolone will be administered at a target dose of 500 mg beginning on the day of transplant, and tapered to 250 mg day 1 post-transplant, 125 mg day 2 post-transplant, 60 mg day 3 post-transplant, 30 mg day 4 post-transplant and day 5 post-transplant 0 mg if therapeutic tacrolimus level achieved for groups 1 and 3.
basiliximab
Basiliximab will be administered in two doses of 20 mg each.
mycophenolate mofetil
Mycophenolate Mofetil will be administered at a target dose of 1000 mg orally twice a day. Myfortic® (mycophenolate sodium) may be used as a replacement for MMF. Mycophenolate sodium will be dosed at 720 mg PO BID. Mycophenolate sodium will be adjusted based on clinical complications.
tacrolimus
The site investigator will identify a starting tacrolimus dose at their discretion, in order to achieve the target trough levels, no later than 5 days post-transplantation. The dose will be adjusted to 5-8ng/ml for the active comparator arm (thymoglobulin + tacrolimus + MMF arm) or tapered off in the experimental arm (basiliximab + 20 weeks of tacrolimus + MMF + belatacept).
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Ability to understand and provide written informed consent;
* Candidate for primary renal allograft from either living or deceased donor;
* No known contraindications to study therapy using NULOJIX® (belatacept);
* Female participants of childbearing potential must have a negative pregnancy test upon study entry;
* Participants with reproductive potential must agree to use an appropriate method(s) of birth control as outlined in the CellCept® , Myfortic® or generic package labeling during participation in the study and for 4 months following completion of the study;
* No donor specific antibodies prior to transplant that are considered to be of clinical significance by the site investigator;
* Negative crossmatch or Panel Reactive Antibodies (PRA) of 0% on historic and current sera, as determined by each participating study center;
* A documented negative tuberculosis (TB) test within the 6 months prior to transplant. If documentation is not present at the time of transplantation, and the subject does not have any risk factors for TB, a TB-specific interferon gamma release assay (IGRA) may be performed.
Exclusion Criteria
* Recipient of previous organ transplant;
* Epstein-Barr Virus (EBV) seronegative (or unknown) recipients;
* Active infection including hepatitis B, hepatitis C, or human Immunodeficiency Virus (HIV);
* Individuals who have required treatment with prednisone or other immunosuppressive drugs within 1 year prior to transplant;
* Individuals undergoing transplant using organs from extended criteria donor (ECD) or donation after cardiac death (DCD) donors;
* Histocompatibility antigen (HLA) identical living donors;
* Individuals at significant risk of early recurrence of the primary renal disease including focal segmental glomerulosclerosis (FSGS) and membranoproliferative glomerulonephritis (MPGN) type 2 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 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 emboli (PE),
* Unexplained stillborn infant or recurrent spontaneous abortion or other congenital or acquired thrombotic disorder.
At the discretion of the investigator, a history of thrombosis of a dialysis access graft, fistula, or indwelling catheter/device may not be considered an exclusion criterion.
* Any condition that, in the opinion of the investigator, would interfere with the participant's ability to comply with study requirements;
* Use of investigational drugs within 4 weeks of enrollment;
* Known hypersensitivity to mycophenolate mofetil (MMF)or any of the drug's components;
* Administration of live attenuated vaccine(s) within 8 weeks of enrollment;
* Blood type A2 and A2B donors into blood type B recipients.
18 Years
65 Years
ALL
No
Sponsors
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Clinical Trials in Organ Transplantation
NETWORK
National Institute of Allergy and Infectious Diseases (NIAID)
NIH
Responsible Party
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Principal Investigators
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Kenneth Newell, MD, PhD
Role: PRINCIPAL_INVESTIGATOR
Emory University
Roslyn B. Mannon, M.D.
Role: STUDY_CHAIR
University of Alabama at Birmingham
Locations
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University of Alabama at Birmingham
Birmingham, Alabama, United States
University of California, San Francisco
San Francisco, California, United States
Emory University
Atlanta, Georgia, United States
Countries
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References
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Mannon RB, Armstrong B, Stock PG, Mehta AK, Farris AB, Watson N, Morrison Y, Sarwal M, Sigdel T, Bridges N, Robien M, Newell KA, Larsen CP. Avoidance of CNI and steroids using belatacept-Results of the Clinical Trials in Organ Transplantation 16 trial. Am J Transplant. 2020 Dec;20(12):3599-3608. doi: 10.1111/ajt.16152. Epub 2020 Jul 13.
Related Links
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National Institute of Allergy and Infectious Diseases (NIAID)
Clinical Trials in Organ Transplantation (CTOT)
Other Identifiers
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DAIT CTOT-16
Identifier Type: -
Identifier Source: org_study_id