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Belatacept Therapy for the Failing Renal Allograft (IM103-133)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01921218
Recruitment Status : Completed
First Posted : August 13, 2013
Results First Posted : January 26, 2021
Last Update Posted : January 26, 2021
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Andrew B Adams, Emory University

Tracking Information
First Submitted Date  ICMJE August 9, 2013
First Posted Date  ICMJE August 13, 2013
Results First Submitted Date  ICMJE December 11, 2020
Results First Posted Date  ICMJE January 26, 2021
Last Update Posted Date January 26, 2021
Study Start Date  ICMJE August 2013
Actual Primary Completion Date December 12, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 6, 2021)
Number of Participants With Donor-specific Antibody Formation [ Time Frame: Month 36 ]
The number of participants in each group with donor-specific antibody formation at 36 months following randomization.
Original Primary Outcome Measures  ICMJE
 (submitted: August 9, 2013)
Development of donor-specific antibody [ Time Frame: 36 months following randomization ]
The rate of donor-specific antibody formation 36 months following randomization.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 6, 2021)
  • Glomerular Filtration Rate (GFR) [ Time Frame: Baseline up to Month 24 ]
    The glomerular filtration rate (GFR) assesses kidney function. GFR uses values for serum creatinine (SCr) measured in mg/dL, age in years, blood urea nitrogen (BUN) measures in mg/dL, and serum albumin (Alb) measured in g/dL. GFR is calculated as 170 x (SCr/0.95)^(-0.999) x (Age)^(-0.176) x (0.762 if the patient is female) x (1.180 if the patient is black) x (BUN)^(-0.170) x (Alb)^(0.318). A value of 90 or above is considered normal while values between 15 and 29 indicate severely decreased kidney function and values below 15 indicate kidney failure. The GFR in participants who do not require dialysis will be followed for two years.
  • Time to Initiation of Dialysis [ Time Frame: Up to Year 2 ]
    Time to dialysis is measured as the time of randomization to initiation of dialysis. Participants already requiring dialysis at the time of enrollment were excluded from this endpoint analysis.
  • Number of Participants With Anti-human Leukocyte Antigen (HLA) Alloantibodies [ Time Frame: Baseline up to Month 36 ]
    The presence of anti-HLA Class I and Class II alloantibodies is categorized as being negative (absent for both classes of alloantibodies), positive for Class I, positive for Class II, and positive for both Class I and Class II alloantibodies.
  • Number of Infectious Complications [ Time Frame: Baseline up to Month 36 ]
    The number of infections complications occurring among study participants is presented here.
Original Secondary Outcome Measures  ICMJE
 (submitted: August 9, 2013)
preservation of glomerular filtration rate [ Time Frame: randomization to initiation of dialysis ]
Rate of change of glomerular filtration rate between treatment and control arms
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Belatacept Therapy for the Failing Renal Allograft
Official Title  ICMJE Belatacept Therapy for the Failing Renal Allograft
Brief Summary The purpose of this study is to test the safety and effectiveness of belatacept (Nulojix®) in preventing antibody formation in patients with chronic failing kidney transplants. This study is a randomized study of first-time kidney transplant patients who have worsening kidney function and biopsy proven grade 2 or 3 interstitial fibrosis/tubular atrophy (IF/TA). Patients must be eligible to get a second transplant. They must have completed or be actively undergoing evaluation for re-listing for a second transplant. Patients will be randomized to either convert to belatacept or continue on calcineurin inhibitor-based therapy.
Detailed Description

The purpose of this study is to test the safety and effectiveness of the medicine belatacept (Nulojix®) in preventing antibodies from forming in people with a failing kidney transplant. Kidney transplant patients take immunosuppression medicines to prevent kidney rejection. When a kidney transplant begins to fail, the immunosuppression medicines are slowly weaned. Once dialysis is started, the immunosuppressant medicines are usually stopped. After immunosuppression is stopped, some people form antibodies. Antibodies are proteins that the immune system makes to protect against harmful foreign substances like bacteria, viruses, or foreign tissues, like a transplant. High levels of antibodies can make it harder to find a kidney donor for that person.

Participants will be randomized into one of the two treatment groups. One group will continue taking their current immunosuppression medicines. The people in the treatment group will be switched to belatacept (Nulojix®). Belatacept (Nulojix®) is an immunosuppression medicine that is approved by the U.S. Food and Drug Administration (the FDA) to prevent rejection in kidney transplant. Participants will stop taking calcineurin inhibitors (either cyclosporine or tacrolimus) or sirolimus but will keep taking other immunosuppression medicines like Cellcept (MMF) or azathioprine (Imuran) and prednisone. These medicines will be slowly weaned and will be stopped if the participant has to start dialysis. Participants will continue taking belatacept (Nulojix®), even while on dialysis.

The study team will test both groups to see how many people in each group develop antibodies.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Failing Renal Allograft
Intervention  ICMJE
  • Drug: Belatacept
    Belatacept, dosing 10mg/kg- day 0, 2 weeks, 1 month, 2 months, 3 months; subsequent doses 5mg/kg monthly through duration of trial or until retransplantation, whichever is first.
    Other Name: Nulojix
  • Drug: Calcineurin inhibitor therapy
    Upon enrollment, wean calcineurin inhibitor (CNI) to target tacrolimus trough of 3-5 nanogram/milliliter (ng/ml)or equivalent cyclosporine trough. Upon initiation of hemodialysis, discontinue CNI therapy over 5 days.
    Other Names:
    • tacrolimus
    • cyclosporine
  • Drug: Mycophenolate mofetil
    Continue current dose at enrollment. Upon initiation of dialysis, decrease dose by half, then discontinue 2 weeks later
    Other Name: Cellcept
  • Drug: prednisone
    Begin steroid withdrawal one month after initiation of dialysis, with monthly reduction in dose by half, with plans to discontinue prednisone by 3 months after initiation of dialysis
    Other Name: Deltasone
Study Arms  ICMJE
  • Experimental: Treatment
    Belatacept (Nulojix) IV
    Interventions:
    • Drug: Belatacept
    • Drug: Mycophenolate mofetil
    • Drug: prednisone
  • Active Comparator: Control
    Calcineurin inhibitor based therapy (cyclosporine or tacrolimus)
    Interventions:
    • Drug: Calcineurin inhibitor therapy
    • Drug: Mycophenolate mofetil
    • Drug: prednisone
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 8, 2020)
13
Original Estimated Enrollment  ICMJE
 (submitted: August 9, 2013)
72
Actual Study Completion Date  ICMJE December 12, 2019
Actual Primary Completion Date December 12, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Signed written informed consent
  • Kidney transplant recipient (human leukocyte antigen (HLA) non-identical donor) who now has impaired renal allograft function with:
  • Estimated glomerular filtration rate (GFR) < 35 with a decline in GFR of > 10% in the 12 months prior to enrollment and must have biopsy proven grade II or III interstitial fibrosis/tubular atrophy (IF/TA) OR
  • Estimated GFR persistently < 20 ml/min over the 6 month period prior to enrollment absent other causes for graft dysfunction, and deemed to have a failing allograft by the patient's transplant nephrologist
  • On a maintenance immunosuppressive regimen that includes calcineurin inhibitor (CNI)(tacrolimus or cyclosporine) or sirolimus and at least
  • MMF of a dose of at least 1 gm/day or comparable dose of azathioprine OR
  • Prednisone at a dose of at least 5 mg/day
  • Men and women, ages 18 to 70, inclusive

Exclusion Criteria:

  • Women of childbearing potential (WOCBP) who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 8 weeks after the last dose of study drug.
  • Women who are pregnant or breastfeeding.
  • Women with a positive pregnancy test.
  • Sexually active fertile men not using effective birth control if their partners are WOCBP.
  • Subjects who are Epstein-Barr Virus (EBV) seronegative.
  • Subjects with any prior solid organ (e.g., heart, liver, pancreas) or cell (e.g., islet, bone marrow) transplant other than a renal allograft. Exception may be made for recipient of a simultaneous kidney-pancreas transplant who had previously experienced graft loss of the pancreas allograft due to thrombosis or rejection.
  • Subjects with presence of donor specific antibody at the time of enrollment
  • Subjects who have a recent history (within 1 yr) of biopsy proven acute rejection > Banff grade Ia
  • Subjects who have a living donor identified for re-transplant within 3 months
  • Subjects with a history of post-transplant lymphoproliferative disease (PTLD)
  • Subjects at risk for tuberculosis (TB)
  • Subjects with a history of cancer within the past 3 years, other than non-melanoma skin cancer(s)
  • Subjects with a positive BK virus serum polymerase chain reaction (PCR) > 20,000 copies at the time of enrollment OR history of biopsy-proven BK nephropathy within the year prior to enrollment.
  • Subjects with a mammogram that is suspicious for malignancy and in whom the possibility of malignancy cannot be reasonably excluded following additional clinical, laboratory, or other diagnostic evaluations
  • Subjects who have difficult intravenous access or other reasons that would likely preclude the ability to receive long-term intravenous infusions
  • Hypersensitivity to any medications that will be used in the protocol
  • Subjects who have used any investigational drug within the 30 days prior to anticipated enrollment
  • Subjects currently receiving belatacept as part of their maintenance immunosuppressive regimen
  • Prisoners, or subjects who are involuntarily incarcerated.
  • Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01921218
Other Study ID Numbers  ICMJE IRB00060470
IM103-133 ( Other Identifier: Bristol-Myers Squibb )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Andrew B Adams, Emory University
Study Sponsor  ICMJE Andrew B Adams
Collaborators  ICMJE Bristol-Myers Squibb
Investigators  ICMJE
Principal Investigator: Andrew B Adams, MD, PhD Emory University
PRS Account Emory University
Verification Date January 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP