A Study in Maintenance Kidney Transplant Recipients Following Conversion to Nulojix® (Belatacept)-Based

Phase 3

Completed

• Conditions: Kidney Transplantation
• Interventions: Drug: Tacrolimus; Drug: Belatacept; Drug: Cyclosporine

• Registration Number: NCT01820572
• Lead Sponsor: Bristol-Myers Squibb

Brief Summary

The primary purpose is to assess the benefits and risks of changing from Cyclosporine or Tacrolimus to Belatacept between 6-60 months after kidney transplant.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2013-03-14
• Study Start: 2013-03-27
• Study First Submitted QC: 2013-03-27
• Study First Posted: 2013-03-29
• Primary Completion: 2019-10-24
• Study Completion: 2019-10-24
• Results First Submitted: 2020-10-22
• Status Verified: 2020-12
• Results First Submitted QC: 2020-12-08
• Last Update Submitted: 2020-12-08
• Results First Posted: 2021-01-05
• Last Update Posted: 2021-01-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 446

Inclusion Criteria

• Men and women, ages 18-75 inclusive
• Adult recipients of a renal allograft from a living donor or a deceased donor between 6-60 months prior to enrollment
• Receiving a stable (≥1 month) regimen of Calcineurin inhibitor (CNI) [Cyclosporine A (CsA) or Tacrolimus (TAC)] with Mycophenolate mofetil (MMF) or Enteric Coated Mycophenolate Sodium (EC-MPS)/Mycophenolic acid (MPA), and corticosteroids
• Stable renal function for 12 weeks prior to enrollment without new onset proteinuria
• Calculated glomerular filtration rate (cGFR) ≥30 and ≤75 mL/min/1.73 m2 [Modification of Diet in Renal Disease study (MDRD) 4-formula]

Exclusion Criteria

• Recipients with Epstein-Barr virus (EBV) serostatus negative or unknown
• History of acute rejection (AR) within 3 months prior to enrollment
• History of antibody mediated rejection
• Positive T-cell lymphocytotoxic cross match
• Proteinuria >1 g/day or >0.5 g/day if diabetic

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
CNI	Tacrolimus	Tacrolimus 4-11 ng/mL tablet orally according to package insert for 24 months Cyclosporine 50-250 ng/mL tablet orally according to package insert for 24 months
CNI	Cyclosporine	Tacrolimus 4-11 ng/mL tablet orally according to package insert for 24 months Cyclosporine 50-250 ng/mL tablet orally according to package insert for 24 months
Belatacept	Belatacept	Belatacept 5 mg/kg intravenous 30 minute infusion on Days 1, 15, 29, 43, 57 then every 28 days for 24 months

Primary Outcome Measures

Name	Time	Method
Percentage of Participants Who Survive With a Functional Graft at 24 Months	at 24 Months	Percentage of participants who survive with a functional graft at 24 months post-randomization

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Marked Laboratory Abnormalities	24 Months	Number of participants with Marked Laboratory Abnormalities
Percentage of Participants Who Survive With a Functional Graft at 12 Months	at 12 Months	Percentage of participants who survive with a functional graft at 12 months post-randomization
Number of Participants With a Biopsy Proven Acute Rejection (BPAR)	at 12 and 24 Months	The number of clinically suspected, biopsy proven acute rejection (AR) at 12 and 24 months post-randomization; includes participants with at least one cellular and/or humoral BPAR event.
Number of Participants With Varying Severity of BPAR	at 12 and 24 months	Number of participants in each severity of clinically suspected, biopsy proven acute rejection (AR) at 12 and 24 months post-randomization
Mean Change From Baseline of Calculated Glomerular Filtration Rate (cGFR) - Percent Change	at 12 and 24 months	Mean change from baseline cGFR as calculated by the 4-variable MDRD equation to 12 and 24 months post-randomization - Percent Change
Percentage of Participants With > 5% and >10% Improvement Over Baseline cGFR	at 12 and 24 Months	Percentage of participants with \> 5% and \>10% improvement over baseline cGFR, at 12 and 24 months post-randomization
Mean Change From Baseline of Calculated Glomerular Filtration Rate (cGFR) - Adjusted Change	at 12 and 24 months	Mean change from baseline cGFR as calculated by the 4-variable MDRD equation to 12 and 24 months post-randomization - Adjusted Change
Mean Urine Protein/ Creatinine Ratio (UPCR)	Up to 24 Months	Urine protein/ creatinine ratio (UPCR) at baseline, 3, 6, 12 and 24 months post randomization
Mean Change From Baseline in Systolic and Diastolic Blood Pressure	at 12 and 24 months	Mean change in systolic and diastolic blood pressure from baseline to 12 and 24 months post randomization
Number of Antihypertensive Medications Used to Control Hypertension	at baseline, 12 and 24 Months	The total number of antihypertensive medications used to control hypertension
Number of Participants With Donor Specific Antibodies (DSA)	at baseline, 12 and 24 months	Number of participants with donor specific antibodies (DSA) at Baseline/Day 1, and Months 12 and 24 post-randomization
Mean Calculated Glomerular Filtration Rate (cGFR)	up to 24 months	Mean cGFR by study visit, as calculated by the 4-variable MDRD equation.
Slope Analysis of cGFR	at 12 and 24 Months	Slopes of cGFR as plotted from baseline as well as from Month 3, to Month 12 and Month 24 post-randomization
Slope Analysis of 1/Serum Creatinine	at 12 and 24 Months	Slopes of 1/serum creatinine as plotted from baseline as well as from Month 3, to Month 12 and Month 24 post-randomization
Mean Number of Symptom Occurrence and Symptom Distress	up to 12 Months	The frequency of symptom occurrence and symptom distress as measured with the Modified Transplant Symptom Occurrence and Symptom Distress Scale-59R (MTSOSD-59R) at baseline, Week 6, and Months 3, 6, and 12 post-randomization.; Higher scores in the MTSOSD-59R indicate a greater symptom and symptom distress burden than lower scores.
Number of Participants With an Adverse Event of Special Interest	24 Months	Number of participants with an adverse event of special interests. Adverse events of special interest include: Serious Infections, Post-Transplant Lymphoproliferative Disorder (PTLD), Progressive multifocal leukoencephalopathy (PML), Malignancies (other than PTLD) including non-melanoma skin carcinomas, Tuberculosis Infections, CNS infections, Viral Infections and Infusion related reactions.
Mean Change From Baseline in Vital Signs: Heart Rate	at 12 and 24 months	The mean change from baseline in measured heart rate

Trial Locations

Locations (62)

UAB Division of Nephrology; 🇺🇸 Birmingham, Alabama, United States

Mayo Clinic Hospital; 🇺🇸 Phoenix, Arizona, United States

Loma Linda University Medical Center (LLUMC) - Children's Hospital - Transplantation Institute; 🇺🇸 Loma Linda, California, United States

UCLA Kidney Transplant Research Office; 🇺🇸 Los Angeles, California, United States

Keck Medical Center of USC (PI Address); 🇺🇸 Los Angeles, California, United States

Cedars-Sinai Medical Center; 🇺🇸 Los Angeles, California, United States

Transplant Research Institute (PI Address); 🇺🇸 Los Angeles, California, United States

University of California, San Francisco (UCSF)-Kidney Transplant Service; 🇺🇸 Sacramento, California, United States

California Institute Of Renal Research; 🇺🇸 San Diego, California, United States

California Pacific Medical Center, Depart of Transplantation (PI Address); 🇺🇸 San Francisco, California, United States

Scroll for more (52 remaining)