A Phase 2 interventional study of Thymoglobulin and Belatacept in Disorder Related to Renal Transplantation, sponsored by Bristol-Myers Squibb. Completed at 17 sites in 3 countries. Open to participants aged 18 Years to 70 Years. Per ClinicalTrials.gov, last updated 2014-06-09.
Sponsored by Bristol-Myers Squibb · Phase 2, Interventional, and Treatment
The purpose of this clinical research study is to learn if belatacept (BMS-224818) is expected to show acceptable rates of acute rejection (AR) in steroid-free belatacept-based immunosuppressive regiments compared to a similar steroid-free tacrolimus regimen. The long-term safety and tolerability of belatacept based regimens following long-term administration in subjects who have received a kidney transplant
Bristol-Myers Squibb is the lead sponsor of 1,538 studies on the registry; 116 are open to participants now.
Of its 429 completed or terminated interventional studies of FDA-regulated products, 223 (52%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
thymoglobulin 1.5mg/kg for 4 days;IV belatacept: 10 mg/kg Days 1 and 5, then every other week through Month 3 (Weeks 2,4,6,8,10,12), and then every 4 weeks through Month 6 (Weeks 16, 20, 24),after 6 months, 5 mg/kg every 4 weeks until 12 months; MMF 1g twice daily(bis in die, BID)
Drug: Thymoglobulin · Drug: Belatacept · Drug: Mycophenolate Mofetil (MMF)
thymoglobulin 1.5mg/kg for 4 days;IV belatacept: 10 mg/kg Days 1 and 5, then every other week through Month 3 (Weeks 2,4,6,8,10,12), and then every 4 weeks through Month 6 (Weeks 16, 20, 24),after 6 months, 5 mg/kg every 4 weeks until 12 months;sirolimus 5 mg/day on Day 1 (day of transplant)and continued through Day 2, dosing to be adjusted to keep pre-dose C0 levels at 7-12 ng/mL for first 6 months, followed by 5 - 10 ng/mL until 12 months.
Drug: Thymoglobulin · Drug: Belatacept · Drug: Sirolimus
(IMPs as comparator regimen)thymoglobulin 1.5mg/kg for 4 days; oral tacrolimus 0.1 mg/kg/day in 2 divided doses with initial targeted trough level of 8-12 ng/mL for Days 1 - 30 with dose reduction to achieve 12 hour trough target of 5-10 ng/mL for 12 months; MMF (mycophenolate mofetil) 1g BID.
Drug: Thymoglobulin · Drug: Tacrolimus · Drug: Mycophenolate Mofetil (MMF)
Induction therapy, IV infusion, All subjects will receive thymoglobulin 1.5-mg/kg i.v. infusion on Days 1 (day of transplant), 2, 3, and 4 (up to a maximum total dose of 6 mg/kg) i.v. infusion over at least 4 hours
Belatacept arms will receive i.v. belatacept (10 mg/kg) on Days 1 and 5, and then every other week through Month 3 (Weeks 2, 4, 6, 8, 10, and 12), and then every 4 weeks through Month 6 (Weeks 16, 20, and 24). After 6 months, subjects will receive belatacept at the maintenance dose of 5 mg/kg every 4 weeks until completion of the trial
Also known as: BMS-224818
Sirolimus will be initiated at 5 mg/day on Day 1 (day of transplant) and continued through Day 2. The dosing will be adjusted subsequently to keep pre-dose (C0) levels at 7 - 12 ng/mL for the first 6 months, followed by 5 - 10 ng/mL thereafter
The recommended total initial dose of tacrolimus is 0.1 mg/kg/day in two divided doses orally up to and including week 52. Post week 52 subjects assigned to the tacrolimus arm will receive tacrolimus orally in accordance with local practice and the package insert until completion of the trial
Administered orally in a capsule or solution formulation in 2 divided doses on a consistent schedule in relation to time of day and meals. The dose should be 1 g bid; however 1.5 g bid may be administered at the investigator's discretion until completion of the trial
Number of Participants With Acute Rejection (AR) of Transplant up to 6 Months Post Transplantation - Intent to Treat (ITT) Population
AR is clinicopathological event requiring clinical evidence and biopsy confirmation by central pathologist. One or more conditions were met and a renal biopsy revealed histologic evidence of rejection: unexplained rise of serum creatine (SCr) greater than or equal to 25% from baseline plus one or more of the following: unexplained decreased urine output; fever, graft tenderness; SCr that remained elevated 14 days post-transplantation and clinical suspicion of AR; other reason and participant treated for episode. Day 1=transplantation. Banff 97 working classification of kidney transplant pathology: Type I=tubulointerstitial AR without arteritis (IA: interstitial infiltration with \>25% of parenchyma affected and moderate tubulitis with \>4 mononuclear cells/tubular cross section; IB: \>10 mononuclear cells; Type II vascular AR with (IA) intimal arteritis (IIA=mild - moderate; IIB=severe; Type III=severe rejection with transmural arterial changes, necrosis of smooth muscle cells.
Time frame: Day 1 to Month 6 post-transplantation
Number of Participants With Acute Rejection of Transplant up to Month 12 Post Transplantation - Intent to Treat Population
AR defined as a clinicopathological event requiring clinical evidence and biopsy confirmation by central pathologist. One or more conditions were met and a renal biopsy revealed histologic evidence of rejection: unexplained rise of serum creatine (SCr) \>= 25 % from baseline plus one or more of the following: unexplained decreased urine output; fever and graft tenderness; a SCr that remained elevated within 14 days after transplantation and clinical suspicion of AR; reason other than those listed and participant was treated for this episode. Day 1 was day of transplantation. Banff grade used Banff 97 working classification of kidney transplant pathology. ITT population was all randomized and transplanted participants.
Time frame: Day 1 to Month 12 post transplantation
Number of Participants With Graft Loss or Death up to Month 6 and Month 12 Post Transplantation - Intent to Treat Population
Graft loss was defined as either functional loss or physical loss. Functional loss was defined as either: sustained level of SCr greater than or equal to (\>=) 6.0 mg/dL (530 micromoles/Liter; micromol/L) for \>= 4 weeks as determined by the local laboratory; regularly scheduled dialysis treatments over a period of 56 days; impairment of renal function to such a degree that the participant undergoes re-transplant. Day 1 was day of transplantation. ITT population defined as all participants randomized and transplanted.
Time frame: Day 1 to Month 6 and Month 12 post transplantation
Number of Participants With Composite of Death, Graft Loss and Acute Rejection up to Month 6 - Intent to Treat Population
Participants with graft loss or death prior to Month 6 were considered having an event of AR, therefore, the incidence of AR was reported as a composite of AR, death, and graft loss.
Time frame: Day 1 up to Month 6
Number of Participants With Composite of Death, Graft Loss and Acute Rejection up to Month 12 - Intent to Treat Population
Subjects with graft loss or death prior to Month 12 were considered having an event of AR, therefore, the incidence of AR was reported as a composite of AR, death, and graft loss.
Time frame: Day 1 up to Month 12
Number of Participants With Delayed Graft Function - Intent to Treat Population
Delayed graft function (DGF) is defined as participant requiring dialysis within the first week (Day 1-8) post transplantation. Participants losing their graft less than 48 hours post transplant and receiving chronic dialysis were not considered as having DGF. Day 1 was day of transplantation. Intent to treat population defined as all participants randomized and transplanted
Time frame: From Day 1 up to and including Day 8 post transplantation
Number of Participants With New Onset Diabetes Mellitus From Baseline to Month 12 Post Transplantation - Intent to Treat Population
Baseline defined as day before transplantation. A participant who did not have diabetes prior to randomization and received an antidiabetic medication for a duration of at least 30 days or a participant who meets the following criteria and did not have diabetes prior to randomization: Symptoms of diabetes plus casual plasma glucose (PG) concentration ≥ 200 mg/dL (11.1 mmol/L); or fasting plasma glucose ≥ 126 mg/dL (7.0 mmol/L); or 2-hour PG ≥ 200 mg/dL (11.1 mmol/L) during an oral glucose tolerance test and a confirmatory laboratory test based on measurements of venous PG must have been done on another day in the absence of unequivocal hyperglycemia accompanied by acute metabolic decompensation. Intent to treat population included all participants randomized and transplanted.
Time frame: Baseline to Month 12
Number of Participants Who Used Anti-hypertension Medications at Baseline and at 12 Months Post Transplantation - Intent to Treat Population
Baseline was defined as day prior to transplantation. Number of anti-hypertension medications taken were categorized from 1 to 6 and greater than (\>)6. Intent to treat population included all participants randomized and transplanted.
Time frame: Baseline and Month 12
Mean Systolic, Diastolic and Arterial Blood Pressure at Baseline and Month 12 - Intent to Treat Population
Systolic, diastolic and mean arterial blood pressures were measured in millimeters of mercury (mm Hg). Baseline was defined as value obtained before transplantation. Intent to treat population included all participants randomized and transplanted.
Time frame: Baseline and 12 months post transplantation
Number of Participants Using Antihyperlipidemic Medications at Month 12 - Intent to Treat Population
Participants using \> = 1 antihyperlipidemic medication at Month 12.
Time frame: Month 12
Mean Change From Baseline (BL) to Month 12 Post Transplantation in Lipid Values - Intent to Treat Population
Baseline (BL) was value obtained day prior to transplantation. Lipid values measured in milligrams/deciliter (mg/dL) included: high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), non-HDL cholesterol (non-HDL-C), total cholesterol (TC), triglycerides. Intent to treat population included all participants randomized and transplanted.
Time frame: Baseline to Month 12
Mean (Standard Deviation) in Calculated Glomerular Filtration Rate (GFR) mL/Min/1.73m^2 at Month 3, Month 6 and Month 12 Post Transplantation - Intent to Treat Population
Blood urea nitrogen (BUN) in mg/dL; Albumin (Alb) in g/dL;Serum creatinine (SCr) in mg/dL; Age in years. Glomerular filtration rate (GFR) was calculated based upon serum creatinine (SCr) using the Modification of Diet in Renal Disease (MDRD) formula as suggested by Levey et al: MDRD GFR = 170 x \[SCr/0.95\]\^(-0.999) x \[Age\]\^(-0.176) x \[0.762 if participant was female\] x \[1.180 if participant was black\] x \[BUN\]\^(-0.170) x \[Alb\]\^(+0.318). Intent to Treat (ITT) population is defined as all participants randomized and transplanted.
Time frame: Months 3, 6 and 12 post transplantation
Number of Corticosteroid-free Participants at 6 and 12 Months Post Transplantation - Intent to Treat Population
Participants were said to be corticosteroid-free at Month 6 if they were not receiving corticosteroids for greater than (\>) 7 consecutive days during Days 141 through Days 196, and at Month 12 if not receiving corticosteroids for \> 7 days during Days 337 through 392. Intent to treat population included all randomized and transplanted participants.
Time frame: Day 1 through Month 12
Number of Participants Who Were Corticosteroid-free at Months 6 and 12 and Number of Participants Who Were Both Calcineurin Inhibitor-free (CNI-free)and Corticosteroid-free at Months 6 and 12 Post Transplantation - Intent to Treat Population
Participants were said to be CNI-free at Month 6 or 12 if they were not receiving a CNI during Day 141 to Day 196, or Day 337 to Day 392. Participants in the tacrolimus arm were not relevant to this analysis because tacrolimus is a calcinurin inhibitor. Participants were corticosteroid-free (CS-free) at Month 6 if they were not receiving corticosteroids for \> 7 consecutive days during Days 141 through Days 196, and at Month 12 if not receiving corticosteroids for \> 7 days during Days 337 through 392. Day 1 was day of transplantation. Intent to treat population included all randomized and transplanted participants.
Time frame: Day 1 to Month 12 post transplantation
Number of Participants With Acute Rejection of Transplant up to End of Month 48 Post Transplantation - Intent to Treat Population in Long Term Extension
AR defined as a clinicopathological event requiring clinical evidence and biopsy confirmation by central pathologist. One or more conditions were met and a renal biopsy revealed histologic evidence of rejection: unexplained rise of serum creatine (SCr) \>= 25 % from baseline plus one or more of the following: unexplained decreased urine output; fever and graft tenderness; a SCr that remained elevated within 14 days after transplantation and clinical suspicion of AR; reason other than those listed and participant was treated for this episode. Day 1 was day of transplantation. Banff grade used Banff 97 working classification of kidney transplant pathology. ITT population was all randomized and transplanted participants.
Time frame: End of Month 12 to end of Month 48 Post Transplantation
Number of Participants With Graft Loss or Death at Months 24, 36, 48 Post Transplantation - Intent to Treat Population in Long Term Extension
Graft loss was defined as either functional loss or physical loss. Functional loss was defined as either: sustained level of SCr greater than or equal to (\>=) 6.0 mg/dL (530 micromoles/Liter; micromol/L) for \>= 4 weeks as determined by the local laboratory; regularly scheduled dialysis treatments over a period of 56 days; impairment of renal function to such a degree that the participant undergoes re-transplant. Day 1 was day of transplantation. ITT population defined as all participants randomized and transplanted.
Time frame: End of Month 12 to end of Long Term Extension (Year 4)
Mean (Standard Deviation) in Calculated Glomerular Filtration Rate (GFR) mL/Min/1.73m^2 at Months 24, 36 and 48 Post Transplantation - Intent to Treat Population in Long Term Extension
GFR was calculated based upon serum creatinine (SCr) using the Modification of Diet in Renal Disease (MDRD) formula as suggested by Levey et al: MDRD GFR = 170 x \[SCr/0.95\]\^(-0.999) x \[Age\]\^(-0.176) x \[0.762 if participant was female\] x \[1.180 if participant was black\] x \[BUN\]\^(-0.170) x \[Alb\]\^(+0.318). Age in years, Alb = Albumin in g/dL; SCr = in mg/dL; BUN =Blood urea nitrogen in mg/dL. Intent to Treat population is defined as all participants randomized and transplanted.
Time frame: Months 24, 36 and 48 post transplantation
Number of Corticosteroid-free Participants at Months 24, 36, 48 Post Transplantation - Intent to Treat Population in Long Term Extension
In the LTE, a participant was considered corticosteroid-free if they were not receiving corticosteroids for \>7 consecutive days during Day 701 and Day 756, Day 1065 and Day 1120, as well as Day 1429 and Day 1484, respectively.
Time frame: End of Month 12 to end of Long Term Extension (Year 4)
Number of Participants Who Were Both Calcineurin Inhibitor-free (CNI-free)and Corticosteroid-free at Months 24, 36, 48 Post Transplantation - Intent to Treat Population in Long Term Extension
Participants were considered corticosteroid-free at Months 24, 36, and 48 if they were not receiving corticosteroids for \>7 consecutive days during Day 701 and Day 756, Day 1065 and Day 1120, as well as Day 1429 and Day 1484, respectively. Participants were considered CNI-free at Months 24, 36, and 48 if they were not receiving CNI during Day 701 and Day 756, Day 1065 and Day 1120, as well as Day 1429 and Day 1484, respectively. Participants in the tacrolimus arm were not relevant to this analysis because tacrolimus is a calcinurin inhibitor.
Time frame: Months 24, 36, 48
Number of Participants Who Switched Between MMF and Sirolimus During Long Term Extension up to Study Completion
Long Term extension was the period from the end of Month 12 to the end of Month 48 post transplantation and the completion of the study 31 July 2012. At any time in the study, participants who were unable to tolerate MMF in the Bela-MMF and Tac-MMF groups could discontinue (DC) MMF and switch to sirolimus and remain in the study and those in the Bela-Siro group who were unable to tolerate sirolimus could DC sirolimus and switch to MMF and remain in the study. Study completion=data base (DB) lock.
Time frame: End of Month 12 to end of Study (Month 48)
First 6 months (July 2007 to October 2008) assessed acute rejection of the renal transplant up to that time. All outcome measures were also assessed at 12 months post transplantation. Participants who wished to continue into the long term extension (LTE) signed a new consent form and were evaluated at 24, 36, and 48 Months post transplantation.
| Milestone | Belatacept, Mycophenolate Mofetil (MMF) | Belatacept, Sirolimus | Tacrolimus, MMF |
|---|---|---|---|
| Started | 33 | 26 | 30 |
| Completed | 27 | 21 | 28 |
| Not completed | 6 | 5 | 2 |
| Withdrew: Adverse event | 2 | 5 | 0 |
| Withdrew: Withdrawal by subject | 0 | 0 | 1 |
| Withdrew: Lack of efficacy | 4 | 0 | 0 |
| Withdrew: Other | 0 | 0 | 1 |
| Milestone | Belatacept, Mycophenolate Mofetil (MMF) | Belatacept, Sirolimus | Tacrolimus, MMF |
|---|---|---|---|
| Started | 27 | 19 | 27 |
| Completed | 25 | 16 | 20 |
| Not completed | 2 | 3 | 7 |
| Withdrew: Adverse event | 0 | 1 | 1 |
| Withdrew: Withdrawal by subject | 1 | 0 | 1 |
| Withdrew: Death | 1 | 1 | 0 |
| Withdrew: No longer met criteria | 0 | 0 | 1 |
| Withdrew: Subject request or refused | 0 | 0 | 3 |
| Withdrew: Poor non-compliance | 0 | 1 | 0 |
| Withdrew: Non-specified | 0 | 0 | 1 |
AR is clinicopathological event requiring clinical evidence and biopsy confirmation by central pathologist. One or more conditions were met and a renal biopsy revealed histologic evidence of rejection: unexplained rise of serum creatine (SCr) greater than or equal to 25% from baseline plus one or more of the following: unexplained decreased urine output; fever, graft tenderness; SCr that remained elevated 14 days post-transplantation and clinical suspicion of AR; other reason and participant treated for episode. Day 1=transplantation. Banff 97 working classification of kidney transplant pathology: Type I=tubulointerstitial AR without arteritis (IA: interstitial infiltration with \>25% of parenchyma affected and moderate tubulitis with \>4 mononuclear cells/tubular cross section; IB: \>10 mononuclear cells; Type II vascular AR with (IA) intimal arteritis (IIA=mild - moderate; IIB=severe; Type III=severe rejection with transmural arterial changes, necrosis of smooth muscle cells.
| participants | Belatacept, Mycophenolate Mofetil (MMF) | Belatacept, Sirolimus | Tacrolimus, MMF |
|---|---|---|---|
| Total Number of Participants with AR | 4 (3.4 to 28.2) | 1 (0.1 to 19.6) | 1 (0.1 to 17.2) |
| Mild Acute IA | 0 | 0 | 0 |
| Mild Acute IB | 0 | 0 | 0 |
| Moderate Acute IIA | 2 | 0 | 1 |
| Moderate Acute IIB | 1 | 1 | 0 |
AR defined as a clinicopathological event requiring clinical evidence and biopsy confirmation by central pathologist. One or more conditions were met and a renal biopsy revealed histologic evidence of rejection: unexplained rise of serum creatine (SCr) \>= 25 % from baseline plus one or more of the following: unexplained decreased urine output; fever and graft tenderness; a SCr that remained elevated within 14 days after transplantation and clinical suspicion of AR; reason other than those listed and participant was treated for this episode. Day 1 was day of transplantation. Banff grade used Banff 97 working classification of kidney transplant pathology. ITT population was all randomized and transplanted participants.
| participants | Belatacept, Mycophenolate Mofetil (MMF) | Belatacept, Sirolimus | Tacrolimus, MMF |
|---|---|---|---|
| Total number of participants with AR | 5 (2.9 to 27.4) | 1 (0.1 to 19.6) | 1 (0.1 to 17.2) |
| Mild Acute IA | 0 | 0 | 0 |
| Mild Acute IB | 0 | 0 | 0 |
| Moderate Acute IIA | 3 | 0 | 1 |
| Moderate Acute IIB | 2 | 1 | 0 |
Graft loss was defined as either functional loss or physical loss. Functional loss was defined as either: sustained level of SCr greater than or equal to (\>=) 6.0 mg/dL (530 micromoles/Liter; micromol/L) for \>= 4 weeks as determined by the local laboratory; regularly scheduled dialysis treatments over a period of 56 days; impairment of renal function to such a degree that the participant undergoes re-transplant. Day 1 was day of transplantation. ITT population defined as all participants randomized and transplanted.
| participants | Belatacept, Mycophenolate Mofetil (MMF) | Belatacept, Sirolimus | Tacrolimus, MMF |
|---|---|---|---|
| Graft loss up to Month 6 post transplantation | 1 | 1 | 0 |
| Graft loss up to Month 12 post transplantation | 2 | 2 | 0 |
| Death up to Month 6 post transplantation | 1 | 0 | 0 |
| Death up to Month 12 post transplantation | 1 | 0 | 0 |
Participants with graft loss or death prior to Month 6 were considered having an event of AR, therefore, the incidence of AR was reported as a composite of AR, death, and graft loss.
| participants | Belatacept, Mycophenolate Mofetil (MMF) | Belatacept, Sirolimus | Tacrolimus, MMF |
|---|---|---|---|
| Number of Participants With Composite of Death, Graft Loss and Acute Rejection up to Month 6 - Intent to Treat Population | 6 | 2 | 1 |
Subjects with graft loss or death prior to Month 12 were considered having an event of AR, therefore, the incidence of AR was reported as a composite of AR, death, and graft loss.
| participants | Belatacept, Mycophenolate Mofetil (MMF) | Belatacept, Sirolimus | Tacrolimus, MMF |
|---|---|---|---|
| Number of Participants With Composite of Death, Graft Loss and Acute Rejection up to Month 12 - Intent to Treat Population | 7 | 3 | 1 |
Delayed graft function (DGF) is defined as participant requiring dialysis within the first week (Day 1-8) post transplantation. Participants losing their graft less than 48 hours post transplant and receiving chronic dialysis were not considered as having DGF. Day 1 was day of transplantation. Intent to treat population defined as all participants randomized and transplanted
| participants | Belatacept, Mycophenolate Mofetil (MMF) | Belatacept, Sirolimus | Tacrolimus, MMF |
|---|---|---|---|
| Number of Participants With Delayed Graft Function - Intent to Treat Population | 6 | 4 | 2 |
Baseline defined as day before transplantation. A participant who did not have diabetes prior to randomization and received an antidiabetic medication for a duration of at least 30 days or a participant who meets the following criteria and did not have diabetes prior to randomization: Symptoms of diabetes plus casual plasma glucose (PG) concentration ≥ 200 mg/dL (11.1 mmol/L); or fasting plasma glucose ≥ 126 mg/dL (7.0 mmol/L); or 2-hour PG ≥ 200 mg/dL (11.1 mmol/L) during an oral glucose tolerance test and a confirmatory laboratory test based on measurements of venous PG must have been done on another day in the absence of unequivocal hyperglycemia accompanied by acute metabolic decompensation. Intent to treat population included all participants randomized and transplanted.
| participants | Belatacept, Mycophenolate Mofetil (MMF) | Belatacept, Sirolimus | Tacrolimus, MMF |
|---|---|---|---|
| Number of Participants With New Onset Diabetes Mellitus From Baseline to Month 12 Post Transplantation - Intent to Treat Population | 0 | 2 | 1 |
Baseline was defined as day prior to transplantation. Number of anti-hypertension medications taken were categorized from 1 to 6 and greater than (\>)6. Intent to treat population included all participants randomized and transplanted.
| participants | Belatacept, Mycophenolate Mofetil (MMF) | Belatacept, Sirolimus | Tacrolimus, MMF |
|---|---|---|---|
| Total using at least 1 medication at baseline | 31 | 24 | 28 |
| Total using at least 1 medication at Month 12 | 25 | 20 | 20 |
| Participants using 1 medication at baseline | 10 | 9 | 5 |
| Participants using 1 medication at Month 12 | 11 | 5 | 4 |
| Participants using 2 medications at baseline | 5 | 5 | 8 |
| Participants using 2 medications at Month 12 | 6 | 8 | 13 |
| Participants using 3 medications at baseline | 8 | 5 | 8 |
| Participants using 3 medications at Month 12 | 6 | 5 | 0 |
| Participants using 4 medications at baseline | 3 | 2 | 3 |
| Participants using 4 medications at Month 12 | 1 | 2 | 3 |
| Participants using 5 medications at baseline | 3 | 1 | 2 |
| Participants using 5 medications at Month 12 | 0 | 0 | 0 |
| Participants using 6 medications at baseline | 2 | 2 | 1 |
| Participants using 6 medications at Month 12 | 1 | 0 | 0 |
| Participants using >6 medications at baseline | 0 | 0 | 1 |
| Participants using >6 medications at Month 12 | 0 | 0 | 0 |
Systolic, diastolic and mean arterial blood pressures were measured in millimeters of mercury (mm Hg). Baseline was defined as value obtained before transplantation. Intent to treat population included all participants randomized and transplanted.
| mm Hg | Belatacept, Mycophenolate Mofetil (MMF) | Belatacept, Sirolimus | Tacrolimus, MMF |
|---|---|---|---|
| Systolic blood pressure at baseline | 133.1 ± 26.43 | 126.9 ± 18.72 | 141.8 ± 23.79 |
| Systolic blood pressure at Month 12 | 129.3 ± 19.24 | 131.0 ± 19.88 | 138.2 ± 19.50 |
| Diastolic blood pressure at baseline | 78.6 ± 12.50 | 72.3 ± 11.27 | 75.3 ± 15.08 |
| Diastolic blood pressure at Month 12 | 73.3 ± 11.96 | 75.1 ± 10.71 | 77.6 ± 10.51 |
| Mean Arterial pressure at baseline | 96.8 ± 15.60 | 90.5 ± 12.84 | 97.5 ± 15.87 |
| Mean Arterial pressure at Month 12 | 91.9 ± 12.80 | 93.7 ± 11.64 | 97.8 ± 10.90 |
Participants using \> = 1 antihyperlipidemic medication at Month 12.
| participants | Belatacept, Mycophenolate Mofetil (MMF) | Belatacept, Sirolimus | Tacrolimus, MMF |
|---|---|---|---|
| Number of Participants Using Antihyperlipidemic Medications at Month 12 - Intent to Treat Population | 11 | 10 | 9 |
Baseline (BL) was value obtained day prior to transplantation. Lipid values measured in milligrams/deciliter (mg/dL) included: high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), non-HDL cholesterol (non-HDL-C), total cholesterol (TC), triglycerides. Intent to treat population included all participants randomized and transplanted.
| mg/dL | Belatacept, Mycophenolate Mofetil (MMF) | Belatacept, Sirolimus | Tacrolimus, MMF |
|---|---|---|---|
| HDL-C change from BL to Month 12 | 1.5 ± 12.70 | -3.7 ± 12.94 | -0.5 ± 12.24 |
| Non-HDL-C change from BL to Month 12 | 16.0 ± 45.25 | 16.1 ± 45.15 | 20.5 ± 42.56 |
| LDL-C change from BL to Month 12 | 23.9 ± 38.18 | 25.0 ± 37.17 | 34.0 ± 30.18 |
| Total cholesterol change from BL to Month 12 | 17.5 ± 40.69 | 12.5 ± 49.03 | 20.0 ± 45.80 |
| Triglycerides change from BL to Month 12 | -11.4 ± 63.31 | -1.1 ± 88.88 | -14.2 ± 94.83 |
Blood urea nitrogen (BUN) in mg/dL; Albumin (Alb) in g/dL;Serum creatinine (SCr) in mg/dL; Age in years. Glomerular filtration rate (GFR) was calculated based upon serum creatinine (SCr) using the Modification of Diet in Renal Disease (MDRD) formula as suggested by Levey et al: MDRD GFR = 170 x \[SCr/0.95\]\^(-0.999) x \[Age\]\^(-0.176) x \[0.762 if participant was female\] x \[1.180 if participant was black\] x \[BUN\]\^(-0.170) x \[Alb\]\^(+0.318). Intent to Treat (ITT) population is defined as all participants randomized and transplanted.
| mL/min/1.73m^2 | Belatacept, Mycophenolate Mofetil (MMF) | Belatacept, Sirolimus | Tacrolimus, MMF |
|---|---|---|---|
| Month 3 post transplantation(n=29,24,27) | 57.8 ± 15.41 | 60.5 ± 26.69 | 51.2 ± 14.78 |
| Month 6 post transplantation(n=29,24,25) | 57.5 ± 14.75 | 58.7 ± 28.36 | 51.7 ± 17.80 |
| Month 12 post transplantation(n=27, 23, 29) | 63.6 ± 27.27 | 61.8 ± 30.66 | 54.0 ± 14.95 |
Participants were said to be corticosteroid-free at Month 6 if they were not receiving corticosteroids for greater than (\>) 7 consecutive days during Days 141 through Days 196, and at Month 12 if not receiving corticosteroids for \> 7 days during Days 337 through 392. Intent to treat population included all randomized and transplanted participants.
| participants | Belatacept, Mycophenolate Mofetil (MMF) | Belatacept, Sirolimus | Tacrolimus, MMF |
|---|---|---|---|
| At 6 Months post transplantation | 27 (68.7 to 95.0) | 23 (76.2 to 100.0) | 28 (84.4 to 100.0) |
| At 12 Months post transplantation | 24 (60.0 to 90.0) | 20 (60.7 to 93.1) | 28 (84.4 to 100.0) |
Participants were said to be CNI-free at Month 6 or 12 if they were not receiving a CNI during Day 141 to Day 196, or Day 337 to Day 392. Participants in the tacrolimus arm were not relevant to this analysis because tacrolimus is a calcinurin inhibitor. Participants were corticosteroid-free (CS-free) at Month 6 if they were not receiving corticosteroids for \> 7 consecutive days during Days 141 through Days 196, and at Month 12 if not receiving corticosteroids for \> 7 days during Days 337 through 392. Day 1 was day of transplantation. Intent to treat population included all randomized and transplanted participants.
| participants | Belatacept, Mycophenolate Mofetil (MMF) | Belatacept, Sirolimus | Tacrolimus, MMF |
|---|---|---|---|
| CS-free Month 6 (N=33, 26, 30) | 27 | 23 | 28 |
| CS-free Month 12 (N=32, 26, 30) | 24 | 20 | 28 |
| CNI-free + CS-free Month 6 (N=32, 26, 30) | 25 | 19 | 1 |
| CNI -free + CS-free Month 12 (N=32,26,30) | 24 | 18 | 1 |
AR defined as a clinicopathological event requiring clinical evidence and biopsy confirmation by central pathologist. One or more conditions were met and a renal biopsy revealed histologic evidence of rejection: unexplained rise of serum creatine (SCr) \>= 25 % from baseline plus one or more of the following: unexplained decreased urine output; fever and graft tenderness; a SCr that remained elevated within 14 days after transplantation and clinical suspicion of AR; reason other than those listed and participant was treated for this episode. Day 1 was day of transplantation. Banff grade used Banff 97 working classification of kidney transplant pathology. ITT population was all randomized and transplanted participants.
| participants | Belatacept, Mycophenolate Mofetil (MMF) | Belatacept, Sirolimus | Tacrolimus, MMF |
|---|---|---|---|
| Number of Participants With Acute Rejection of Transplant up to End of Month 48 Post Transplantation - Intent to Treat Population in Long Term Extension | 0 | 0 | 0 |
Graft loss was defined as either functional loss or physical loss. Functional loss was defined as either: sustained level of SCr greater than or equal to (\>=) 6.0 mg/dL (530 micromoles/Liter; micromol/L) for \>= 4 weeks as determined by the local laboratory; regularly scheduled dialysis treatments over a period of 56 days; impairment of renal function to such a degree that the participant undergoes re-transplant. Day 1 was day of transplantation. ITT population defined as all participants randomized and transplanted.
| participants | Belatacept, Mycophenolate Mofetil (MMF) | Belatacept, Sirolimus | Tacrolimus, MMF |
|---|---|---|---|
| Graft Loss or Death at Month 24 (N=27,19,27) | 0 | 1 | 0 |
| Graft Loss or Death at Month 36 (N=27,19,27) | 1 | 2 | 0 |
| Graft Loss or Death at Month 48 (N=27,19,27) | 1 | 2 | 0 |
GFR was calculated based upon serum creatinine (SCr) using the Modification of Diet in Renal Disease (MDRD) formula as suggested by Levey et al: MDRD GFR = 170 x \[SCr/0.95\]\^(-0.999) x \[Age\]\^(-0.176) x \[0.762 if participant was female\] x \[1.180 if participant was black\] x \[BUN\]\^(-0.170) x \[Alb\]\^(+0.318). Age in years, Alb = Albumin in g/dL; SCr = in mg/dL; BUN =Blood urea nitrogen in mg/dL. Intent to Treat population is defined as all participants randomized and transplanted.
| mL/Min/1.73m^2 | Belatacept, Mycophenolate Mofetil (MMF) | Belatacept, Sirolimus | Tacrolimus, MMF |
|---|---|---|---|
| Month 24 (N=27, 18, 27) | 60.6 ± 15.12 | 66.0 ± 23.75 | 52.2 ± 12.14 |
| Month 36 (N=25, 16, 22) | 62.8 ± 14.05 | 69.9 ± 22.43 | 55.5 ± 15.38 |
| Month 48 (N=18, 14, 15) | 59.6 ± 15.30 | 72.2 ± 25.21 | 55.7 ± 13.47 |
In the LTE, a participant was considered corticosteroid-free if they were not receiving corticosteroids for \>7 consecutive days during Day 701 and Day 756, Day 1065 and Day 1120, as well as Day 1429 and Day 1484, respectively.
| participants | Belatacept, Mycophenolate Mofetil (MMF) | Belatacept, Sirolimus | Tacrolimus, MMF |
|---|---|---|---|
| Month 24 (N=27, 18, 27) | 22 | 15 | 25 |
| Month 36 (N=26, 16, 23) | 22 | 14 | 20 |
| Month 48 (N=19, 14, 16) | 16 | 12 | 16 |
Participants were considered corticosteroid-free at Months 24, 36, and 48 if they were not receiving corticosteroids for \>7 consecutive days during Day 701 and Day 756, Day 1065 and Day 1120, as well as Day 1429 and Day 1484, respectively. Participants were considered CNI-free at Months 24, 36, and 48 if they were not receiving CNI during Day 701 and Day 756, Day 1065 and Day 1120, as well as Day 1429 and Day 1484, respectively. Participants in the tacrolimus arm were not relevant to this analysis because tacrolimus is a calcinurin inhibitor.
| participants | Belatacept, Mycophenolate Mofetil (MMF) | Belatacept, Sirolimus | Tacrolimus, MMF |
|---|---|---|---|
| Month 24 (N=27, 18, 27) | 22 | 15 | 0 |
| Month 36 (N=26, 16, 23) | 22 | 14 | 0 |
| Month 48 (N=19, 14, 16) | 16 | 12 | 0 |
Long Term extension was the period from the end of Month 12 to the end of Month 48 post transplantation and the completion of the study 31 July 2012. At any time in the study, participants who were unable to tolerate MMF in the Bela-MMF and Tac-MMF groups could discontinue (DC) MMF and switch to sirolimus and remain in the study and those in the Bela-Siro group who were unable to tolerate sirolimus could DC sirolimus and switch to MMF and remain in the study. Study completion=data base (DB) lock.
| participants | Belatacept, Mycophenolate Mofetil (MMF) | Belatacept, Sirolimus | Tacrolimus, MMF |
|---|---|---|---|
| By Month 24 Switched between MMF and Sirolimus | 0 (0 to 0) | 1 (0.1 to 26.0) | 0 (0 to 0) |
| By Month 36 Switched between MMF and Sirolimus | 0 (0 to 0) | 2 (1.3 to 33.1) | 0 (0 to 0) |
| By Month 48 Switched between MMF and Sirolimus | 0 (0 to 0) | 3 (3.4 to 39.6) | 0 (0 to 0) |
| Up to DB Lock Switched between MMF and Sirolimus | 0 (0 to 0) | 3 (3.4 to 39.6) | 0 (0 to 0) |
Collected over From Day 1 to end of 48 Months post transplantation and study closure. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Belatacept - MMF | — | 25/33 (75.8%) | 33/33 (100%) |
| Belatacept - SIRO | — | 19/26 (73.1%) | 26/26 (100%) |
| Tacrolimus - MMF | — | 22/30 (73.3%) | 30/30 (100%) |
| Event | Belatacept - MMF | Belatacept - SIRO | Tacrolimus - MMF |
|---|---|---|---|
| Squamous cell carcinomaNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 1/33 | 0/26 | 4/30 |
| DiarrhoeaGastrointestinal disorders | 1/33 | 3/26 | 2/30 |
| Urinary tract infectionInfections and infestations | 3/33 | 0/26 | 2/30 |
| PyrexiaGeneral disorders | 2/33 | 2/26 | 1/30 |
| DehydrationMetabolism and nutrition disorders | 1/33 | 2/26 | 2/30 |
| HydronephrosisRenal and urinary disorders | 1/33 | 2/26 | 1/30 |
| Graft dysfunctionInjury, poisoning and procedural complications | 0/33 | 1/26 | 2/30 |
| UrosepsisInfections and infestations | 0/33 | 0/26 | 2/30 |
| Deep vein thrombosisVascular disorders | 1/33 | 1/26 | 2/30 |
| Ureteric stenosisRenal and urinary disorders | 0/33 | 0/26 | 2/30 |
| Event | Belatacept - MMF | Belatacept - SIRO | Tacrolimus - MMF |
|---|---|---|---|
| DiarrhoeaGastrointestinal disorders | 13/33 | 17/26 | 21/30 |
| AnaemiaBlood and lymphatic system disorders | 20/33 | 18/26 | 14/30 |
| PyrexiaGeneral disorders | 16/33 | 17/26 | 15/30 |
| Oedema peripheralGeneral disorders | 14/33 | 15/26 | 10/30 |
| Procedural painInjury, poisoning and procedural complications | 19/33 | 11/26 | 13/30 |
| LeukopeniaBlood and lymphatic system disorders | 18/33 | 12/26 | 15/30 |
| ConstipationGastrointestinal disorders | 16/33 | 11/26 | 12/30 |
| HypertensionVascular disorders | 11/33 | 9/26 | 13/30 |
| Urinary tract infectionInfections and infestations | 14/33 | 8/26 | 10/30 |
| NauseaGastrointestinal disorders | 14/33 | 7/26 | 12/30 |
All participants who received transplant and were treated with drug were analyzed up to Month 12 post transplant.
| Age, Categorical(Participants) | Belatacept, Mycophenolate Mofetil (MMF) | Belatacept, Sirolimus | Tacrolimus, MMF | Total |
|---|---|---|---|---|
| <=18 years | 0 | 0 | 0 | 0 |
| Between 18 and 65 years | 33 | 24 | 26 | 83 |
| >=65 years | 0 | 2 | 4 | 6 |
| Age, Continuous(years) | Belatacept, Mycophenolate Mofetil (MMF) | Belatacept, Sirolimus | Tacrolimus, MMF | Total |
|---|---|---|---|---|
| Mean | 49.2 ± 11.1 | 52.7 ± 10.8 | 53.6 ± 13.2 | 51.7 ± 11.8 |
| Sex: Female, Male(Participants) | Belatacept, Mycophenolate Mofetil (MMF) | Belatacept, Sirolimus | Tacrolimus, MMF | Total |
|---|---|---|---|---|
| Female | 8 | 6 | 8 | 22 |
| Male | 25 | 20 | 22 | 67 |
| Region of Enrollment(participants) | Belatacept, Mycophenolate Mofetil (MMF) | Belatacept, Sirolimus | Tacrolimus, MMF | Total |
|---|---|---|---|---|
| North America | 22 | 16 | 20 | 58 |
| Europe | 11 | 10 | 10 | 31 |
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