Clinical trial NCT02560558: Bela 8 Week Dosing
Official title: Belatacept Immunosuppression Therapy in Post-Transplant Kidney Recipients: Comparison of 4-Week and 8-Week Dosing Intervals
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Kidney Transplantation
Keywords: Immunosuppression
Transplantation Immunology
Lead sponsor: Emory University
Sponsor class: OTHER
First posted: 2015-09-25
Enrollment: 166
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: The purpose of this study is to transition patients who have been stable on Belatacept for one year after kidney transplant from standard 4-week to an investigational 8-week belatacept dosing schedule. The investigators hypothesize that renal function and acute rejection rates will be non-inferior with 8-week belatacept dosing.

Detailed description: The current dosing protocol for patients who have undergone a kidney transplant requires that Belatacept be given as an infusion every 4 weeks. The investigator wants to assess if the patients who have been stable for one year after transplant can be safely transitioned to an 8-week Belatacept infusion schedule. Renal function and any episodes of acute rejection will be closely monitored.

Eligibility criteria: Inclusion Criteria:

* Adult (age ≥18 years currently),
* First-time renal transplant recipients of either living donor or deceased donor,

  1. who were initiated on belatacept at the time of transplant and
  2. are at least one year post-transplant and off CNI therapy for at least 6 months.
* Patients at low immunologic risk, defined as

  1. patients with a first transplant who have a PRA \< 50 against class I and class II antigens,
  2. no DSA (donor-specific antibodies),
  3. who have not had more than one episode of rejection, and
  4. no episodes of rejection within the last 6 months prior to enrollment, and
  5. no rejection with a grade of IIB or above.

Exclusion Criteria:

* Not first renal transplant, or multi-organ transplant recipient
* History of greater than one episode of biopsy-proven acute rejection, or of rejection of Banff 97 grade IIB or greater, or rejection within the last 6 months.
* Pregnancy (women of childbearing potential must use adequate contraception during study)
* Unwilling to receive all belatacept infusions at the Emory Transplant Center
* Calculated Glomerular Filtration Rate (GFR) less than 35.
* Serum creatinine at enrollment over 30% higher than 3 months (±4 weeks) prior to randomization
* HbA1C greater than 8 at enrollment
* Recent history of significant proteinuria (protein/Cr ratio \>1)
* Non-standard belatacept dosing (e.g. dose other than 5 mg belatacept/kg body weight)
* Cellcept dose less than 500 mg po bid.
* Prednisone dose greater than 5mg po qd within 3 months of randomization
* Patients not currently taking prednisone
* Active infection, or antibiotic or antiviral drug therapy within 1 month of randomization
* Evidence of Cytomegalovirus (CMV) viremia or clinical CMV infection within last 3 months.
* Polyomavirus BK PCR (polymerase chain reaction) load greater then 4.3 (copy number greater than 20,0000) within 3 months of randomization
* Known hepatitis B surface antigen-positive or PCR-positive for hepatitis B (testing not required)
* Known HIV (human immunodeficiency virus infection) (testing not required)
* Presence of donor specific antibody by Luminex single antigen assessment, or panel reactivity (PRA) above 50%.
* History of substance abuse or psychiatric disorder not compatible with study adherence and follow up.

Primary outcomes:
measure: Mean Estimated Glomerular Filtration Rate (eGFR) at 12 Months From Baseline
timeFrame: 12 months from baseline
Secondary outcomes:
measure: Number of Participants With Transplant Rejection at 6 Months and 12 Months Post Baseline
timeFrame: 6 months post baseline, 12 months post baseline
measure: Number of Subjects With Grade IIA and Lower Rejections at 6 Months and 12 Months Post Baseline
timeFrame: 6 months post baseline, 12 months post baseline
measure: Number of Subjects With Grade IIB and Higher Rejections at 6 Months and 12 Months Post Baseline
timeFrame: 6 months post baseline, 12 months post baseline
measure: Number of Deaths at 6 Months and 12 Months Post Baseline
timeFrame: 6 months post baseline, 12 months post baseline
measure: Number of Subjects That Experienced Graft Loss at 6 Moths and 12 Months Post Baseline
timeFrame: 6 months post baseline, 12 months from baseline
measure: Number of Subjects With Human Leukocyte Antigen Donor Specific Antibodies (HLA DSA) at 6 Months and 12 Months Post Baseline
timeFrame: 6 moths post baseline, 12 months post baseline
measure: Number of Clinic Visits
timeFrame: At 12 months from baseline
measure: Number of Subjects Needing Hospitalizations
timeFrame: At 12 months from baseline
measure: Number of Subjects Needing Transplant Biopsies at 12 Months Post Baseline
timeFrame: 12 months post baseline
measure: Cost Analysis
timeFrame: At 12 months from baseline
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Emory Clinic
state: Georgia
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
Study officials:
affiliation: Emory University
name: Idelberto Badell, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Knight SR. Transplant Trial Watch. Transpl Int. 2021 Jul;34(7):1171-1173. doi: 10.1111/tri.13928.
citation: Badell IR, Parsons RF, Karadkhele G, Cristea O, Mead S, Thomas S, Robertson JM, Kim GS, Hanfelt JJ, Pastan SO, Larsen CP. Every 2-month belatacept maintenance therapy in kidney transplant recipients greater than 1-year posttransplant: A randomized, noninferiority trial. Am J Transplant. 2021 Sep;21(9):3066-3076. doi: 10.1111/ajt.16538. Epub 2021 Mar 17.