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

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ClinicalTrials.gov Identifier: NCT01921218
Recruitment Status : Active, not recruiting
First Posted : August 13, 2013
Last Update Posted : November 28, 2018
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Andrew B Adams, MD, PhD, Emory University

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.

Condition or disease Intervention/treatment Phase
Failing Renal Allograft Drug: Belatacept Drug: Calcineurin inhibitor therapy Drug: Mycophenolate mofetil Drug: prednisone Phase 3

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 72 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Belatacept Therapy for the Failing Renal Allograft
Study Start Date : August 2013
Estimated Primary Completion Date : January 2020
Estimated Study Completion Date : January 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Belatacept

Arm Intervention/treatment
Experimental: Treatment
Belatacept (Nulojix) IV
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: 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

Active Comparator: Control
Calcineurin inhibitor based therapy (cyclosporine or tacrolimus)
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




Primary Outcome Measures :
  1. Comparison of development of donor-specific antibody between groups [ Time Frame: 36 months following randomization ]
    The rate of donor-specific antibody formation 36 months following randomization, compared between groups.


Secondary Outcome Measures :
  1. Change of glomerular filtration rate between groups [ Time Frame: Randomization to initiation of dialysis (up to 2 years) ]
    Change of glomerular filtration rate (GFR) between treatment and control arms. Participants not requiring dialysis initiation will be followed for two years.



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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Signed Written Informed Consent
  • Kidney transplant recipient (non-HLA identical donor) who now has impaired renal allograft function with:
  • Estimated 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:

  • 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 serum 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01921218


Locations
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United States, Georgia
Emory University
Atlanta, Georgia, United States, 30322
Sponsors and Collaborators
Andrew B Adams, MD, PhD
Bristol-Myers Squibb
Investigators
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Principal Investigator: Andrew B Adams, MD, PhD Emory University

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Responsible Party: Andrew B Adams, MD, PhD, Assistant Professor of Surgery, Emory University
ClinicalTrials.gov Identifier: NCT01921218     History of Changes
Other Study ID Numbers: IRB00060470
IM103-133 ( Other Identifier: Bristol-Myers Squibb )
First Posted: August 13, 2013    Key Record Dates
Last Update Posted: November 28, 2018
Last Verified: November 2018

Keywords provided by Andrew B Adams, MD, PhD, Emory University:
Kidney transplant

Additional relevant MeSH terms:
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Prednisone
Mycophenolic Acid
Tacrolimus
Cyclosporins
Cyclosporine
Abatacept
Calcineurin Inhibitors
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antifungal Agents
Anti-Infective Agents
Dermatologic Agents
Antirheumatic Agents
Antibiotics, Antineoplastic
Antibiotics, Antitubercular
Antitubercular Agents
Anti-Bacterial Agents