Regimen Optimization Study

• Sponsor: Bristol-Myers Squibb (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02137239
• Collaborator: (none)
• Enrollment: 58
• Locations: 20
• Arms: 2
• Actual Duration (Months): 40
• Patients Per Site: 2.9
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Patients who undergo a kidney transplant require prolonged therapy with drugs that suppress the immune system (called immunosuppressive regimens) to stop the immune system from attacking the transplanted kidney in order to limit damage to or the possibility of rejecting the transplanted kidney. The purpose of this study is to evaluate benefits and risks of two immunosuppressive regimens (belatacept with everolimus or tacrolimus with mycophenolate mofetil) following thymoglobulin induction and rapid corticosteroid withdrawal.

Condition or Disease	Intervention/Treatment	Phase
Kidney Transplantation	Drug: Thymoglobulin; Drug: Belatacept; Drug: mycophenolate mofetil(MMF); Drug: Corticosteroids; Drug: Everolimus(EVL); Drug: Tacrolimus(TAC)	Phase 2

Detailed Description

Calcineurin inhibitor (CNI)

Study Design

• Study Type: Interventional
• Actual Enrollment: 58 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Evaluation of Acute Rejection Rates in de Novo Renal Transplant Recipients Following Thymoglobulin Induction, CNI-free, Nulojix (Belatacept)-Based Immunosuppression
• Actual Study Start Date: Dec 31, 2015
• Actual Primary Completion Date: May 2, 2019
• Actual Study Completion Date: May 2, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Belatacept + Everolimus Thymoglobulin (i.v. infusion) induction, daily (or less frequently, as tolerated) not to exceed 10 days, to reach a total cumulative dose between 3.0 and 5.5 mg/kg; belatacept (infusion) regimen of 10 mg/kg i.v. on Day 1, Weeks 1, 2, 4, 8 and 12 post transplant and then a maintenance dose of 5 mg/kg every 4 weeks after 12 weeks post transplant; everolimus (tablet) daily dosing at 3.0 mg/day, 2 divided doses, starting on Day 3 dosing adjusted based on blood sample tests; methylprednisolone (infusion) prior to each Thymoglobulin infusion and prednisone (tablet), once methylprednisolone is no longer needed. (Corticosteroids to be discontinued by Day 7 or as soon thereafter as thymoglobulin infusions are completed)	Drug: Thymoglobulin; Other Names: ATG ; Drug: Belatacept; Other Names: Nulojix ; Drug: Corticosteroids; Other Names: Methylprednisolone Prednisone ; Drug: Everolimus(EVL); Other Names: Certican® Zortress®
Experimental: Tacrolimus + Mycophenolate mofetil Thymoglobulin (i.v. infusion) induction, daily (or less frequently, as tolerated) not to exceed 10 days, to reach a total cumulative dose between 3.0 and 5.5 mg/kg; tacrolimus (tablet) daily dosing beginning at 0.1 mg/kg/day, then adjusted based on blood sample tests; MMF (tablet) daily dosing between 0.5 to 2.0 g/day divided in 2 doses (up to 3 g/day if African Americans/Blacks); methylprednisolone (infusion) prior to each Thymoglobulin infusion and prednisone (tablet), once methylprednisolone is no longer needed. (Corticosteroids to be discontinued by Day 7 or as soon thereafter as thymoglobulin infusions are completed)	Drug: Thymoglobulin; Other Names: ATG ; Drug: mycophenolate mofetil(MMF); Other Names: CellCept ; Drug: Corticosteroids; Other Names: Methylprednisolone Prednisone ; Drug: Tacrolimus(TAC); Other Names: Prograf

Outcome Measures

Primary Outcome Measures

1. Percentage of Clinically-suspected Biopsy-proven Acute Rejection (CSBPAR) at 6 Months [6 Months]

   Number of Participants with Clinically-suspected biopsy-proven acute rejection (CSBPAR) at 6 Months

Secondary Outcome Measures

1. Clinically-suspected Biopsy-proven Acute Rejection (CSBPAR) at 6, 12 and 24 Months [Up to 24 Months]

   Clinically-suspected biopsy-proven acute rejection (CSBPAR) at 6, 12 and 24 Months Change in the incidence of CSBPAR at 6, 12 and 24 months post transplant, in the belatacept + EVL(Treatment A) as compared to TAC + MMF (Treatment B).

2. Time to Clinically-suspected Biopsy-proven Acute Rejection (CSBPAR). [Up to 24 Months]

   Time to Clinically suspected biopsy proven acute rejection

3. Percentage of Participants With BANFF Grade by Severity Grades. BANFF Type (Grade) for Acute/Active Rejection [At 6, 12 and 24 Months]

   Treatment differences in the severity grades to treat all episodes of CSBPAR at 6, 12, and 24 months post-transplant. Type 1A - Cases with significant interstitial infiltration (>25% of parenchyma affected) and foci of moderate tubulitis (>4 mononuclear cells/Tubular cross section or group of 10 Tubular cell). Type 1B - Cases with significant interstitial infiltration (>25% of parenchyma affected) and foci of moderate tubulitis (>10 mononuclear cells/Tubular cross section or group of 10 Tubular cell).Type 2A - Cases with mild to moderate intimal arteritis.Type 2B - Cases with severe intimal arteritis comprising >25% of the luminal area. Type 3 - Cases with "transmural" arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells (v3 with accompanying lymphocytic inflammation)

4. Treatment Differences in Therapeutic Modalities [at 6, 12 and 24 Months]

   Treatment Received for Biopsy Proven Acute Rejection (Banff Grade IA or Higher), or Humoral (Antibody Mediated) Rejection Treatment regimen: Categorical analysis of CSBPAR episodes by treatment received.

5. Number of Participants Who Survive With a Functioning Graft [At 6, 12 and 24 months]

   Number of all participants who survive with a functioning graft at 6, 12 and 24 months post transplant

6. Number of Participants Deaths Post Transplant [up to 24 months]

   Number of participant deaths at 6, 12 and 24 months post transplant

7. Number of Participants Who Experience Graft Loss Post Transplant [At 6, 12 and 24 months]

   Number of all participants who experience graft loss at 6, 12 and 24 months post transplant

8. Time to Event: Graft Loss and Death [Up to 728 Days]

   The Number of days to participant Graft Loss and death for any reason

9. Absolute Calculated Glomerular Filtration Rate (cGFR): Mean [Up 24 Months post-transplant]

   Absolute (mean and median) cGFR values at 3, 6, 12 and 24 months post-transplant, as determined from the 4-variable Modification of Diet in Renal Disease (MDRD) formula

10. Median Calculated Glomerular Filtration Rate (cGFR) [Up 24 Months post-transplant]

    Median cGFR values at 3, 6, 12 and 24 months post-transplant, as determined from the 4-variable Modification of Diet in Renal Disease (MDRD) formula

11. Mean Change From Month 3 in cGFR [Up 24 Months post-transplant]

    The mean change from Month 3 cGFR at 3, 6, 12 and 24 months post-transplant

12. Urine Protein Creatinine Ratio (UPr/Cr) [Up 24 Months post-transplant]

    Urine protein to creatinine ratio (UPr/Cr) at 3, 6, 12 and 24 months post-transplant.

13. Percentage of Participants With Donor Specific Anti-HLA Antibodies (DSA) [Up to 24 Months]

    Percentage of participants with, and titers of pre-existing (pre-transplant) DSA on Day 1 (pre-transplant, pre-dose), and at Months 12 and 24 posttransplant

14. Percentage of Participants With De Novo Donor Specific Anti-HLA Antibodies (DSA) [Up to 24 Months]

    Characterization of any de novo DSA detected by IgM and IgG subclasses, and by the presence or absence of complement fixing properties.

15. Percentage of Participants With Adverse Events (AEs) [Up to 24 months Post-Transplant]

    Percentage of participants with AEs up to 24 months post-transplant

16. Percentage of Participants With Serious Adverse Events (SAEs) [Up to 24 months Post-Transplant]

    Percentage of participants with SAEs up to 24 months post-transplant

17. Percentage of Participants With Events of Special Interest (ESIs) [Up to 24 Months]

    Percentage of participants which have one of the following events of special interest: Serious Infections Post-Transplant Lymphoproliferative Disorder (PTLD) Progressive multifocal leukoencephalopathy (PML) Malignancies (Other than PTLD) including non-melanoma skin carcinomas (Malignancies) Tuberculosis Infections Central Nervous System (CNS) Infections Viral Infections Infusion Related reactions within 24 hours since belatacept infusion

18. Percentage of Particpants With Laboratory Test Abnormalities (LTAs) [At 24 Months]

    Percentage of participants with laboratory tests with marked laboratory abnormalities

19. Mean and Mean Change From Baseline in Blood Glucose [Up to 24 months]

    Mean fasting blood glucose levels, and mean changes from baseline values at Months 6, 12 and 24 months post- transplant

20. Mean and Mean Change From Baseline in Whole Blood HbA1c [Up to 24 months]

    Mean whole blood HbA1C concentrations, and mean changes from baseline values at Months 6, 12 and 24 months post-transplant.

21. Percentage of Participants With New Onset Diabetes After Transplant [up to 24 months]

    Percentage of participants with New Onset Diabetes After Transplantation (NODAT) at 6, 12, and 24 months post-transplant.

22. Absolute Values of Blood Pressure: Mean [Up to 24 Months]

    Absolute (mean and median) values for SBP and DBP at 3, 6, 12 and 24 months posttransplant;

23. Absolute Values of Blood Pressure: Median [Up to 24 Months]

    Absolute (mean and median) values for SBP and DBP at 3, 6, 12 and 24 months posttransplant;

24. Mean Changes From Baseline Values for Blood Pressure [Up to 24 Months]

    Mean changes from baseline values for SBP and DBP at 6, 12 and 24 months post-transplant

25. Absolute Values of Fasting Lipid Values: Mean [Up to 24 Months]

    Absolute (mean and median) values at 3, 6, 12 and 24 months post-transplant for the following: Serum total cholesterol (TC) Serum high density lipoprotein (HDL) cholesterol Serum low density lipoprotein (LDL) cholesterol Serum triglycerides (TG)

26. Absolute Values of Fasting Lipid Values: Median [Up to 24 Months]

    Absolute (mean and median) values at 3, 6, 12 and 24 months post-transplant for the following: Serum total cholesterol (TC) Serum high density lipoprotein (HDL) cholesterol Serum low density lipoprotein (LDL) cholesterol Serum triglycerides (TG)

27. Mean Changes From Baseline Values of Lipid Values [at months 12 and 24]

    Mean changes from baseline values in the following: Serum total cholesterol (TC) Serum high density lipoprotein (HDL) cholesterol Serum low density lipoprotein (LDL) cholesterol Serum triglycerides (TG)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

• Men and women, aged 18 to 75

• Serologic test results are positive for past exposure to Epstein Barr Virus (EBV+)

• Diagnosed with end stage renal disease (ESRD) and scheduled to undergo transplantation of a non-HLA identical, living or standard criteria deceased donor kidney

Exclusion Criteria:

• Primary cause of ESRD is: primary focal segmental glomerulosclerosis; or Type I or II membranoproliferative glomerulonephritis; or Hemolytic Uremic Syndrome / Thrombotic Thrombocytopenic Purpura

• Had a previous graft loss due to acute rejection

• At increased immunologic risk of graft loss due to panel reactive antibodies (PRA)

20% or need for desensitization therapy

• Scheduled to receive a: kidney from identical twin; or paired kidney; or kidney from a Cytomegalovirus(CMV) positive donor when recipient is CMV negative; or kidney from an extended criteria donor

• Have a body mass index (BMI) of > 35 kg/m2 for nondiabetics or > 30 kg/m2 for diabetics

• Diagnosed as Hepatitis B positive; or Hepatitis C positive; or HIV positive; or currently or previously active or inadequately treated latent

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	California Institute Of Renal Research	San Diego	California	United States	92123
2	California Pacific Medical Center	San Francisco	California	United States	94115
3	University Of Colorado	Aurora	Colorado	United States	80045
4	Yale University	New Haven	Connecticut	United States	06519
5	MedStar Georgetown University Hospital	Washington	District of Columbia	United States	20007
6	Emory Univeristy	Atlanta	Georgia	United States	30322
7	University Of Illinois	Chicago	Illinois	United States	60612
8	Tulane Medical Center	New Orleans	Louisiana	United States	70112
9	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
10	Saint Barnabas Medical Center	Livingston	New Jersey	United States	07039
11	Erie County Medical Center	Buffalo	New York	United States	14215
12	Wake Forest University School Of Medicine	Winston-Salem	North Carolina	United States	27157
13	Central PA Transplant Foundation	Harrisburg	Pennsylvania	United States	17104
14	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37232
15	University of Virginia	Charlottesville	Virginia	United States	22908-0709
16	Inova Fairfax Hospital	Falls Church	Virginia	United States	22042
17	Swedish Medical Center - Swedish Colon and Rectal Clinic - First Hill (Northwest Colon and Rectal Cl	Seattle	Washington	United States	98104
18	Sanatorio Parque S.A.	Rosario	Santa Fe	Argentina	2000
19	Clinica Privada Velez Sarsfield	Cordoba		Argentina	5016
20	Clinica De Nefrologia, Urologia Y Enf. Cardiovasculares	Sante Fe		Argentina	3000

Sponsors and Collaborators

• Bristol-Myers Squibb

Investigators

• Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Study Documents (Full-Text)

• Study Protocol - Aug 14, 2017
• Statistical Analysis Plan - Jun 26, 2019

More Information

Additional Information:

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

Publications

None provided.

• Responsible Party: Bristol-Myers Squibb
• ClinicalTrials.gov Identifier: NCT02137239
• Other Study ID Numbers: IM103-177; 2013-002090-21
• First Posted: May 13, 2014
• Last Update Posted: Jun 22, 2021
• Last Verified: May 1, 2021

• Additional relevant MeSH terms: Mycophenolic Acid; Prednisone; Methylprednisolone; Everolimus; Abatacept; Tacrolimus; Thymoglobulin

Study Results

Participant Flow

Pre-assignment Detail	58 participants randomized and treated

Arm/Group Title	Treatment A	Treatment B
Arm/Group Description	BELA + EVL	TAC + MMF
Period Title: Overall Study
STARTED	26	32
COMPLETED	23	26
NOT COMPLETED	3	6

Baseline Characteristics

Arm/Group Title	Treatment A	Treatment B	Total
Arm/Group Description	BELA + EVL	TAC + MMF	Total of all reporting groups
Overall Participants	26	32	58
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	51.7 (12.8)	50.8 (10.9)	51.2 (11.7)
Age, Customized (Count of Participants)
< 65	22 84.6%	28 87.5%	50 86.2%
≥ 65	4 15.4%	4 12.5%	8 13.8%
Sex: Female, Male (Count of Participants)
Female	5 19.2%	9 28.1%	14 24.1%
Male	21 80.8%	23 71.9%	44 75.9%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	3 9.4%	3 5.2%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	3 11.5%	6 18.8%	9 15.5%
White	23 88.5%	21 65.6%	44 75.9%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	2 6.3%	2 3.4%

Outcome Measures

1. Primary Outcome

Title	Percentage of Clinically-suspected Biopsy-proven Acute Rejection (CSBPAR) at 6 Months
Description	Number of Participants with Clinically-suspected biopsy-proven acute rejection (CSBPAR) at 6 Months
Time Frame	6 Months

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Treatment A	Treatment B
Arm/Group Description	BELA + EVL	TAC + MMF
Measure Participants	26	32
Number (95% Confidence Interval) [Percentage of participants]	7.7 29.6%	9.4 29.4%

2. Secondary Outcome

Title	Clinically-suspected Biopsy-proven Acute Rejection (CSBPAR) at 6, 12 and 24 Months
Description	Clinically-suspected biopsy-proven acute rejection (CSBPAR) at 6, 12 and 24 Months Change in the incidence of CSBPAR at 6, 12 and 24 months post transplant, in the belatacept + EVL(Treatment A) as compared to TAC + MMF (Treatment B).
Time Frame	Up to 24 Months

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Treatment A	Treatment B
Arm/Group Description	BELA + EVL	TAC + MMF
Measure Participants	26	32
CSBPAR at 6 Months	7.7	9.4
CSBPAR at 12 months	11.5	12.5
CSBPAR at 24 Months	15.4	12.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment A, Treatment B
	Comments	Change in Incidence of Treatment A as compared to Treatment B at 6 Months
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Incidence of Change
	Estimated Value	-1.7
	Confidence Interval	(2-Sided) 95%; -18.9 to 16.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Treatment A, Treatment B
	Comments	Change in Incidence of Treatment A as compared to Treatment B at 12 Months
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Incidence of Change
	Estimated Value	-1.0
	Confidence Interval	(2-Sided) 95%; -19.2 to 18.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Treatment A, Treatment B
	Comments	Change in Incidence of Treatment A as compared to Treatment B at 24 Months
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Incidence of Change
	Estimated Value	2.9
	Confidence Interval	(2-Sided) 95%; -16.1 to 23.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Time to Clinically-suspected Biopsy-proven Acute Rejection (CSBPAR).
Description	Time to Clinically suspected biopsy proven acute rejection
Time Frame	Up to 24 Months

Outcome Measure Data

Analysis Population Description

Participants with a CSBPAR

Arm/Group Title	Treatment A	Treatment B
Arm/Group Description	BELA + EVL	TAC + MMF
Measure Participants	3	3
Mean (Full Range) [Months]	NA	NA

4. Secondary Outcome

Title	Percentage of Participants With BANFF Grade by Severity Grades. BANFF Type (Grade) for Acute/Active Rejection
Description	Treatment differences in the severity grades to treat all episodes of CSBPAR at 6, 12, and 24 months post-transplant. Type 1A - Cases with significant interstitial infiltration (>25% of parenchyma affected) and foci of moderate tubulitis (>4 mononuclear cells/Tubular cross section or group of 10 Tubular cell). Type 1B - Cases with significant interstitial infiltration (>25% of parenchyma affected) and foci of moderate tubulitis (>10 mononuclear cells/Tubular cross section or group of 10 Tubular cell).Type 2A - Cases with mild to moderate intimal arteritis.Type 2B - Cases with severe intimal arteritis comprising >25% of the luminal area. Type 3 - Cases with "transmural" arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells (v3 with accompanying lymphocytic inflammation)
Time Frame	At 6, 12 and 24 Months

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Treatment A	Treatment B
Arm/Group Description	BELA + EVL	TAC + MMF
Measure Participants	26	32
6 Months: Mild Acute (1A)	3.8 14.6%	0 0%
6 Months: Mild Acute (1B)	0 0%	3.1 9.7%
6 Months: Moderate Acute (2A)	7.7 29.6%	6.3 19.7%
6 Months: Moderate Acute (2B)	0 0%	0 0%
6 Months: Severe Acute	0 0%	0 0%
12 Months: Mild Acute (1A)	7.7 29.6%	3.1 9.7%
12 Months: Mild Acute (1B)	0 0%	3.1 9.7%
12 Months: Moderate Acute (2A)	7.7 29.6%	6.3 19.7%
12 Months: Moderate Acute (2B)	0 0%	0 0%
12 Months: Severe Acute	0 0%	0 0%
24 Months: Mild Acute (1A)	11.5 44.2%	3.1 9.7%
24 Months: Mild Acute (1B)	0 0%	3.1 9.7%
24 Months: Moderate Acute (2A)	7.7 29.6%	6.3 19.7%
24 Months: Moderate Acute (2B)	0 0%	0 0%
24 Months: Severe Acute	0 0%	0 0%

5. Secondary Outcome

Title	Treatment Differences in Therapeutic Modalities
Description	Treatment Received for Biopsy Proven Acute Rejection (Banff Grade IA or Higher), or Humoral (Antibody Mediated) Rejection Treatment regimen: Categorical analysis of CSBPAR episodes by treatment received.
Time Frame	at 6, 12 and 24 Months

Outcome Measure Data

Analysis Population Description

All Randomized, Transplanted and Treated Participants

Arm/Group Title	Treatment A	Treatment B
Arm/Group Description	BELA + EVL	TAC + MMF
Measure Participants	26	32
Corticosteroids (6 months)	7.7 29.6%	9.4 29.4%
Lymphocyte depleting agent (6 months)	0 0%	6.3 19.7%
Plasmapheresis (6 months)	0 0%	0 0%
IVIG (6 months)	0 0%	3.1 9.7%
Rituximab (6 months)	0 0%	0 0%
Corticosteroids (12 months)	15.4 59.2%	12.5 39.1%
Lymphocyte depleting agent (12 months)	3.8 14.6%	6.3 19.7%
Plasmapheresis (12 months)	0 0%	0 0%
IVIG (12 months)	0 0%	3.1 9.7%
Rituximab (12 months)	0 0%	0 0%
Corticosteroids (24 months)	19.2 73.8%	12.5 39.1%
Lymphocyte depleting agent (24 months)	3.8 14.6%	6.3 19.7%
Plasmapheresis (24 months)	0 0%	0 0%
IVIG (24 months)	0 0%	3.1 9.7%
Rituximab (24 months)	0 0%	0 0%

6. Secondary Outcome

Title	Number of Participants Who Survive With a Functioning Graft
Description	Number of all participants who survive with a functioning graft at 6, 12 and 24 months post transplant
Time Frame	At 6, 12 and 24 months

Outcome Measure Data

Analysis Population Description

All Treated Participants

Arm/Group Title	Treatment A	Treatment B
Arm/Group Description	BELA + EVL	TAC + MMF
Measure Participants	26	32
At 6 Months	25 96.2%	31 96.9%
At 12 Months	25 96.2%	31 96.9%
At 24 Months	25 96.2%	31 96.9%

7. Secondary Outcome

Title	Number of Participants Deaths Post Transplant
Description	Number of participant deaths at 6, 12 and 24 months post transplant
Time Frame	up to 24 months

Outcome Measure Data

Analysis Population Description

All Treated Participants

Arm/Group Title	Treatment A	Treatment B
Arm/Group Description	BELA + EVL	TAC + MMF
Measure Participants	26	32
At 6 Months	0 0%	0 0%
At 12 Months	0 0%	0 0%
At 24 Months	0 0%	0 0%

8. Secondary Outcome

Title	Number of Participants Who Experience Graft Loss Post Transplant
Description	Number of all participants who experience graft loss at 6, 12 and 24 months post transplant
Time Frame	At 6, 12 and 24 months

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Treatment A	Treatment B
Arm/Group Description	BELA + EVL	TAC + MMF
Measure Participants	26	32
At 6 Months	1 3.8%	1 3.1%
At 12 Months	1 3.8%	1 3.1%
At 24 Months	1 3.8%	1 3.1%

9. Secondary Outcome

Title	Time to Event: Graft Loss and Death
Description	The Number of days to participant Graft Loss and death for any reason
Time Frame	Up to 728 Days

Outcome Measure Data

Analysis Population Description

All Treated Participants

Arm/Group Title	Treatment A	Treatment B
Arm/Group Description	BELA + EVL	TAC + MMF
Measure Participants	1	1
Graft Loss	107	2

10. Secondary Outcome

Title	Absolute Calculated Glomerular Filtration Rate (cGFR): Mean
Description	Absolute (mean and median) cGFR values at 3, 6, 12 and 24 months post-transplant, as determined from the 4-variable Modification of Diet in Renal Disease (MDRD) formula
Time Frame	Up 24 Months post-transplant

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Treatment A	Treatment B
Arm/Group Description	BELA + EVL	TAC + MMF
Measure Participants	26	32
At 3 Months	69.2	62.2
At 6 Months	66.0	63.9
At 12 Months	66.2	62.0
At 24 Months	71.8	68.7

11. Secondary Outcome

Title	Median Calculated Glomerular Filtration Rate (cGFR)
Description	Median cGFR values at 3, 6, 12 and 24 months post-transplant, as determined from the 4-variable Modification of Diet in Renal Disease (MDRD) formula
Time Frame	Up 24 Months post-transplant

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Treatment A	Treatment B
Arm/Group Description	BELA + EVL	TAC + MMF
Measure Participants	26	32
At 3 Months	64.0	62.0
At 6 Months	64.0	67.0
At 12 Months	66.0	62.5
At 24 Months	73.5	68.0

12. Secondary Outcome

Title	Mean Change From Month 3 in cGFR
Description	The mean change from Month 3 cGFR at 3, 6, 12 and 24 months post-transplant
Time Frame	Up 24 Months post-transplant

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Treatment A	Treatment B
Arm/Group Description	BELA + EVL	TAC + MMF
Measure Participants	26	32
At 3 Months	0	0
At 6 Months	-3.2	2.8
At 12 Months	-3.1	1.4
At 24 Months	3.1	6.3

13. Secondary Outcome

Title	Urine Protein Creatinine Ratio (UPr/Cr)
Description	Urine protein to creatinine ratio (UPr/Cr) at 3, 6, 12 and 24 months post-transplant.
Time Frame	Up 24 Months post-transplant

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Treatment A	Treatment B
Arm/Group Description	BELA + EVL	TAC + MMF
Measure Participants	26	32
At 3 Months	0.3146	0.1412
At 6 Months	0.3896	0.1461
At 12 Months	0.2835	0.1849
At 24 Months	0.3940	0.1685

14. Secondary Outcome

Title	Percentage of Participants With Donor Specific Anti-HLA Antibodies (DSA)
Description	Percentage of participants with, and titers of pre-existing (pre-transplant) DSA on Day 1 (pre-transplant, pre-dose), and at Months 12 and 24 posttransplant
Time Frame	Up to 24 Months

Outcome Measure Data

Analysis Population Description

As Treated Population

Arm/Group Title	Treatment A	Treatment B
Arm/Group Description	BELA + EVL	TAC + MMF
Measure Participants	25	33
Baseline Class 1 DSA	10 38.5%	0 0%
Baseline Class 2 DSA	0 0%	0 0%
Baseline Both Class 1 and 2 DSA	0 0%	0 0%
12 Month Class 1 DSA	8.00 30.8%	0 0%
12 Month Class 2 DSA	0 0%	3.03 9.5%
12 Month Both Class 1 and 2 DSA	0 0%	0 0%
24 Month Class 1 DSA	8.00 30.8%	3.03 9.5%
24 Month Class 2 DSA	0 0%	3.03 9.5%
24 Month Both Class 1 and 2 DSA	0 0%	0 0%

15. Secondary Outcome

Title	Percentage of Participants With De Novo Donor Specific Anti-HLA Antibodies (DSA)
Description	Characterization of any de novo DSA detected by IgM and IgG subclasses, and by the presence or absence of complement fixing properties.
Time Frame	Up to 24 Months

Outcome Measure Data

Analysis Population Description

As Treated Population

Arm/Group Title	Treatment A	Treatment B
Arm/Group Description	BELA + EVL	TAC + MMF
Measure Participants	25	33
Baseline Class 1 DSA	10	0
Baseline Class 2 DSA	0	0
Baseline Both Class 1 and 2 DSA	0	0
De Novo 12 Month Class 1 DSA	0	0
De Novo 12 Month Class 2 DSA	0	0
De Novo 12 Month Both Class 1 and 2 DSA	0	0
De Novo 24 Month Class 1 DSA	0	3.45
De Novo 24 Month Class 2 DSA	0	0
De Novo 24 Month Both Class 1 and 2 DSA	0	0

16. Secondary Outcome

Title	Percentage of Participants With Adverse Events (AEs)
Description	Percentage of participants with AEs up to 24 months post-transplant
Time Frame	Up to 24 months Post-Transplant

Outcome Measure Data

Analysis Population Description

As Treated Population

Arm/Group Title	Treatment A	Treatment B
Arm/Group Description	BELA + EVL	TAC + MMF
Measure Participants	25	33
Number [Percentage of participants with AEs]	100.0 384.6%	97.0 303.1%

17. Secondary Outcome

Title	Percentage of Participants With Serious Adverse Events (SAEs)
Description	Percentage of participants with SAEs up to 24 months post-transplant
Time Frame	Up to 24 months Post-Transplant

Outcome Measure Data

Analysis Population Description

As Treated Population

Arm/Group Title	Treatment A	Treatment B
Arm/Group Description	BELA + EVL	TAC + MMF
Measure Participants	25	33
Number [Percentage of participants with SAEs]	52.0 200%	60.6 189.4%

18. Secondary Outcome

Title	Percentage of Participants With Events of Special Interest (ESIs)
Description	Percentage of participants which have one of the following events of special interest: Serious Infections Post-Transplant Lymphoproliferative Disorder (PTLD) Progressive multifocal leukoencephalopathy (PML) Malignancies (Other than PTLD) including non-melanoma skin carcinomas (Malignancies) Tuberculosis Infections Central Nervous System (CNS) Infections Viral Infections Infusion Related reactions within 24 hours since belatacept infusion
Time Frame	Up to 24 Months

Outcome Measure Data

Analysis Population Description

As Treated Population

Arm/Group Title	Treatment A	Treatment B
Arm/Group Description	BELA + EVL	TAC + MMF
Measure Participants	25	33
Serious Infections	16 61.5%	15.2 47.5%
PTLD	4.0 15.4%	3.0 9.4%
PML	0 0%	0 0%
Malignancies	4.0 15.4%	3.0 9.4%
TB	0 0%	0 0%
CNS Infections	0 0%	0 0%
Viral Infections	0 0%	0 0%
Infusion Related Reactions	1 3.8%	0 0%

19. Secondary Outcome

Title	Percentage of Particpants With Laboratory Test Abnormalities (LTAs)
Description	Percentage of participants with laboratory tests with marked laboratory abnormalities
Time Frame	At 24 Months

Outcome Measure Data

Analysis Population Description

As Treated Population

Arm/Group Title	Treatment A	Treatment B
Arm/Group Description	BELA + EVL	TAC + MMF
Measure Participants	25	33
Hemoglobin (Low)	12.0 46.2%	6.1 19.1%
Leukocytes (low)	0 0%	3.0 9.4%
Lymphocyte (Absolute) (low)	84.0 323.1%	69.7 217.8%
Neutrophils (Absolute) (low)	0 0%	3.0 9.4%
Aspartate Aminotransferase (High)	4.0 15.4%	0 0%
Creatinine (High)	16.0 61.5%	3.0 9.4%
Inorganic Phosphorus (low)	24.0 92.3%	12.1 37.8%
Potassium (high)	4.0 15.4%	0 0%
Sodium (low)	4.0 15.4%	0 0%
Albumin (low)	0 0%	3.0 9.4%
Glucose (high)	8.0 30.8%	12.1 37.8%
Triglycerides (high)	12.0 46.2%	0 0%
Uric Acid (high)	8.0 30.8%	0 0%

20. Secondary Outcome

Title	Mean and Mean Change From Baseline in Blood Glucose
Description	Mean fasting blood glucose levels, and mean changes from baseline values at Months 6, 12 and 24 months post- transplant
Time Frame	Up to 24 months

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Treatment A	Treatment B
Arm/Group Description	BELA + EVL	TAC + MMF
Measure Participants	26	32
Mean Value at 6 months	107.2	107.2
Change from baseline at 6 months	4.9	4.8
Mean Value at 12 months	101.1	127.5
Change from baseline at 12 months	-1.3	20.6
Mean Value at 24 months	127.5	111.8
Change from baseline at 24 months	22.3	15.0

21. Secondary Outcome

Title	Mean and Mean Change From Baseline in Whole Blood HbA1c
Description	Mean whole blood HbA1C concentrations, and mean changes from baseline values at Months 6, 12 and 24 months post-transplant.
Time Frame	Up to 24 months

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Treatment A	Treatment B
Arm/Group Description	BELA + EVL	TAC + MMF
Measure Participants	26	32
Mean Value at 6 months	6.11	6.13
Change from baseline at 6 months	0.34	0.48
Mean Value at 12 months	6.18	6.21
Change from baseline at 12 months	0.47	0.32
Mean Value at 24 months	6.24	6.29
Change from baseline at 24 months	0.66	0.41

22. Secondary Outcome

Title	Percentage of Participants With New Onset Diabetes After Transplant
Description	Percentage of participants with New Onset Diabetes After Transplantation (NODAT) at 6, 12, and 24 months post-transplant.
Time Frame	up to 24 months

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Treatment A	Treatment B
Arm/Group Description	BELA + EVL	TAC + MMF
Measure Participants	26	32
Up to 6 Months	11.5 44.2%	6.3 19.7%
Up to 12 Months	11.5 44.2%	6.3 19.7%
Up to 24 Months	15.4 59.2%	12.5 39.1%

23. Secondary Outcome

Title	Absolute Values of Blood Pressure: Mean
Description	Absolute (mean and median) values for SBP and DBP at 3, 6, 12 and 24 months posttransplant;
Time Frame	Up to 24 Months

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Treatment A	Treatment B
Arm/Group Description	BELA + EVL	TAC + MMF
Measure Participants	26	32
Diastolic Month 3	78.7	77.7
Systolic Month 3	134.2	131.0
Diastolic Month 6	77.4	79.4
Systolic Month 6	128.1	133.0
Diastolic Month 12	78.7	80.1
Systolic Month 12	131.0	131.0
Diastolic Month 24	78.1	78.5
Systolic Month 24	130.9	131.7

24. Secondary Outcome

Title	Absolute Values of Blood Pressure: Median
Description	Absolute (mean and median) values for SBP and DBP at 3, 6, 12 and 24 months posttransplant;
Time Frame	Up to 24 Months

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Treatment A	Treatment B
Arm/Group Description	BELA + EVL	TAC + MMF
Measure Participants	26	32
Diastolic Month 3	78.5	80.0
Systolic Month 3	135.5	131.0
Diastolic Month 6	75.5	80.0
Systolic Month 6	127.0	131.0
Diastolic Month 12	77.0	81.0
Systolic Month 12	130.0	126.0
Diastolic Month 24	78.0	79.0
Systolic Month 24	130.0	130.0

25. Secondary Outcome

Title	Mean Changes From Baseline Values for Blood Pressure
Description	Mean changes from baseline values for SBP and DBP at 6, 12 and 24 months post-transplant
Time Frame	Up to 24 Months

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Treatment A	Treatment B
Arm/Group Description	BELA + EVL	TAC + MMF
Measure Participants	26	32
Diastolic Month 6	1.0	4.8
Systolic Month 6	-4.0	-0.7
Diastolic Month 12	2.3	5.4
Systolic Month 12	-1.1	-3.2
Diastolic Month 24	0.9	2.1
Systolic Month 24	-2.3	-4.2

26. Secondary Outcome

Title	Absolute Values of Fasting Lipid Values: Mean
Description	Absolute (mean and median) values at 3, 6, 12 and 24 months post-transplant for the following: Serum total cholesterol (TC) Serum high density lipoprotein (HDL) cholesterol Serum low density lipoprotein (LDL) cholesterol Serum triglycerides (TG)
Time Frame	Up to 24 Months

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Treatment A	Treatment B
Arm/Group Description	BELA + EVL	TAC + MMF
Measure Participants	26	32
TC Month 3	181.2	174.4
TC Month 6	197.7	175
TC Month 12	189.0	169.9
TC Month 24	193.2	168.2
HDL Month 3	50.6	50.4
HDL Month 6	46.4	53.9
HDL Month 12	49.4	49.6
HDL Month 24	50.1	51.3
LDL Month 3	96.9	96.5
LDL Month 6	115.2	93.7
LDL Month 12	107.5	88.0
LDL Month 24	97.9	91.5
TG Month 3	171.6	137.8
TG Month 6	180.0	138.3
TG Month 12	162.4	161.3
TG Month 24	263.4	145.0

27. Secondary Outcome

Title	Absolute Values of Fasting Lipid Values: Median
Description	Absolute (mean and median) values at 3, 6, 12 and 24 months post-transplant for the following: Serum total cholesterol (TC) Serum high density lipoprotein (HDL) cholesterol Serum low density lipoprotein (LDL) cholesterol Serum triglycerides (TG)
Time Frame	Up to 24 Months

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Treatment A	Treatment B
Arm/Group Description	BELA + EVL	TAC + MMF
Measure Participants	26	32
TC Month 3	167.0	173.0
TC Month 6	187.0	178.0
TC Month 12	184.0	171.5
TC Month 24	193.0	166.0
HDL Month 3	45.0	49.0
HDL Month 6	45.5	49.0
HDL Month 12	50.0	47.0
HDL Month 24	49.0	49.0
LDL Month 3	89.0	95.0
LDL Month 6	99.5	100.0
LDL Month 12	104.0	91.5
LDL Month 24	103.5	86.0
TG Month 3	147.0	128.0
TG Month 6	157.5	126.0
TG Month 12	154.0	130.0
TG Month 24	159.0	114.0

28. Secondary Outcome

Title	Mean Changes From Baseline Values of Lipid Values
Description	Mean changes from baseline values in the following: Serum total cholesterol (TC) Serum high density lipoprotein (HDL) cholesterol Serum low density lipoprotein (LDL) cholesterol Serum triglycerides (TG)
Time Frame	at months 12 and 24

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Treatment A	Treatment B
Arm/Group Description	BELA + EVL	TAC + MMF
Measure Participants	26	32
TC Month 12	25.7	-2.8
TC Month 24	26.6	10.0
HDL Month 12	5.4	1.9
HDL Month 24	6.2	4.8
LDL Month 12	25.7	10.8
LDL Month 24	17.4	15.7
TG Month 12	3.3	-86.1
TG Month 24	106.8	-13.6

Adverse Events

Time Frame	Up to 24 months after last treatment dose
Adverse Event Reporting Description	Because 1 participant ith BPAR had been randomized to the BELA+EVL group, but had then mistakenly been treated with TAC+MMF beginning on Day 1 and continuing through the entire 2-year study period, analysis was also performed using the modified ITT (as-treated) population, in which the participant was analyzed as having received TAC+MMF.
Arm/Group Title	BELA+EVL		TAC+MMF
Arm/Group Description	BELA + EVL		TAC + MMF
All Cause Mortality
	BELA+EVL		TAC+MMF
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/25 (0%)		0/33 (0%)
Serious Adverse Events
	BELA+EVL		TAC+MMF
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/25 (52%)		20/33 (60.6%)
Blood and lymphatic system disorders
Anaemia	1/25 (4%)		1/33 (3%)
Febrile neutropenia	0/25 (0%)		2/33 (6.1%)
Neutropenia	0/25 (0%)		4/33 (12.1%)
Pancytopenia	1/25 (4%)		0/33 (0%)
Cardiac disorders
Arteriospasm coronary	0/25 (0%)		1/33 (3%)
Atrial fibrillation	1/25 (4%)		1/33 (3%)
Gastrointestinal disorders
Abdominal adhesions	0/25 (0%)		1/33 (3%)
Ascites	1/25 (4%)		0/33 (0%)
Diarrhoea	1/25 (4%)		0/33 (0%)
Duodenal ulcer	0/25 (0%)		1/33 (3%)
Gastritis erosive	0/25 (0%)		1/33 (3%)
Incarcerated inguinal hernia	1/25 (4%)		0/33 (0%)
Intra-abdominal fluid collection	1/25 (4%)		0/33 (0%)
Intra-abdominal haematoma	1/25 (4%)		0/33 (0%)
Retroperitoneal haemorrhage	1/25 (4%)		0/33 (0%)
Small intestinal obstruction	0/25 (0%)		1/33 (3%)
Vomiting	1/25 (4%)		0/33 (0%)
Hepatobiliary disorders
Cholecystitis acute	2/25 (8%)		0/33 (0%)
Immune system disorders
Renal transplant failure	0/25 (0%)		1/33 (3%)
Infections and infestations
Cellulitis	1/25 (4%)		0/33 (0%)
Gastroenteritis	0/25 (0%)		1/33 (3%)
Gastroenteritis norovirus	0/25 (0%)		1/33 (3%)
Herpes zoster	0/25 (0%)		1/33 (3%)
Osteomyelitis	0/25 (0%)		1/33 (3%)
Osteomyelitis acute	0/25 (0%)		1/33 (3%)
Pneumonia	1/25 (4%)		0/33 (0%)
Renal graft infection	1/25 (4%)		0/33 (0%)
Septic shock	0/25 (0%)		1/33 (3%)
Urinary tract infection	3/25 (12%)		0/33 (0%)
Injury, poisoning and procedural complications
Overdose	0/25 (0%)		1/33 (3%)
Vascular pseudoaneurysm	1/25 (4%)		0/33 (0%)
Investigations
Blood creatinine increased	1/25 (4%)		3/33 (9.1%)
Weight decreased	1/25 (4%)		0/33 (0%)
Metabolism and nutrition disorders
Diabetes mellitus	0/25 (0%)		1/33 (3%)
Hyponatraemia	0/25 (0%)		1/33 (3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Plasma cell myeloma	0/25 (0%)		1/33 (3%)
Post transplant lymphoproliferative disorder	1/25 (4%)		1/33 (3%)
Nervous system disorders
Central nervous system vasculitis	0/25 (0%)		1/33 (3%)
Cerebellar ataxia	1/25 (4%)		0/33 (0%)
Haemorrhage intracranial	0/25 (0%)		1/33 (3%)
Renal and urinary disorders
Acute kidney injury	0/25 (0%)		2/33 (6.1%)
Bladder stenosis	1/25 (4%)		0/33 (0%)
Haematuria	0/25 (0%)		1/33 (3%)
Hydronephrosis	0/25 (0%)		1/33 (3%)
Nephropathy toxic	1/25 (4%)		0/33 (0%)
Perinephric collection	1/25 (4%)		0/33 (0%)
Proteinuria	0/25 (0%)		1/33 (3%)
Renal artery stenosis	0/25 (0%)		1/33 (3%)
Renal impairment	0/25 (0%)		1/33 (3%)
Renal tubular necrosis	1/25 (4%)		1/33 (3%)
Ureteral necrosis	1/25 (4%)		0/33 (0%)
Skin and subcutaneous tissue disorders
Diabetic foot	1/25 (4%)		0/33 (0%)
Vascular disorders
Dry gangrene	1/25 (4%)		0/33 (0%)
Iliac artery occlusion	1/25 (4%)		0/33 (0%)
Other (Not Including Serious) Adverse Events
	BELA+EVL		TAC+MMF
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	25/25 (100%)		30/33 (90.9%)
Blood and lymphatic system disorders
Anaemia	4/25 (16%)		5/33 (15.2%)
Leukocytosis	0/25 (0%)		2/33 (6.1%)
Leukopenia	8/25 (32%)		7/33 (21.2%)
Neutropenia	1/25 (4%)		2/33 (6.1%)
Thrombocytopenia	0/25 (0%)		2/33 (6.1%)
Cardiac disorders
Atrial fibrillation	4/25 (16%)		1/33 (3%)
Palpitations	2/25 (8%)		0/33 (0%)
Tachycardia	2/25 (8%)		2/33 (6.1%)
Gastrointestinal disorders
Abdominal distension	0/25 (0%)		4/33 (12.1%)
Abdominal pain	2/25 (8%)		3/33 (9.1%)
Abdominal pain lower	1/25 (4%)		2/33 (6.1%)
Abdominal pain upper	2/25 (8%)		1/33 (3%)
Aphthous ulcer	4/25 (16%)		2/33 (6.1%)
Constipation	5/25 (20%)		10/33 (30.3%)
Diarrhoea	4/25 (16%)		10/33 (30.3%)
Dyspepsia	0/25 (0%)		4/33 (12.1%)
Flatulence	1/25 (4%)		2/33 (6.1%)
Gastrooesophageal reflux disease	0/25 (0%)		5/33 (15.2%)
Mouth ulceration	10/25 (40%)		0/33 (0%)
Nausea	5/25 (20%)		13/33 (39.4%)
Vomiting	5/25 (20%)		7/33 (21.2%)
General disorders
Chest pain	2/25 (8%)		0/33 (0%)
Fatigue	4/25 (16%)		3/33 (9.1%)
Oedema peripheral	5/25 (20%)		5/33 (15.2%)
Pyrexia	2/25 (8%)		3/33 (9.1%)
Infections and infestations
BK virus infection	4/25 (16%)		3/33 (9.1%)
Body tinea	2/25 (8%)		0/33 (0%)
Bronchitis	2/25 (8%)		0/33 (0%)
Cytomegalovirus viraemia	0/25 (0%)		2/33 (6.1%)
Fungal infection	2/25 (8%)		0/33 (0%)
Influenza	1/25 (4%)		3/33 (9.1%)
Nasopharyngitis	1/25 (4%)		2/33 (6.1%)
Onychomycosis	2/25 (8%)		0/33 (0%)
Tooth infection	0/25 (0%)		2/33 (6.1%)
Upper respiratory tract infection	2/25 (8%)		2/33 (6.1%)
Urinary tract infection	5/25 (20%)		4/33 (12.1%)
Injury, poisoning and procedural complications
Complications of transplanted kidney	2/25 (8%)		1/33 (3%)
Fall	1/25 (4%)		2/33 (6.1%)
Graft complication	2/25 (8%)		0/33 (0%)
Incision site pain	0/25 (0%)		3/33 (9.1%)
Limb injury	0/25 (0%)		2/33 (6.1%)
Procedural pain	4/25 (16%)		4/33 (12.1%)
Wound	2/25 (8%)		0/33 (0%)
Investigations
Blood alkaline phosphatase increased	2/25 (8%)		0/33 (0%)
Blood bicarbonate decreased	0/25 (0%)		2/33 (6.1%)
Blood creatinine increased	1/25 (4%)		2/33 (6.1%)
Donor specific antibody present	2/25 (8%)		0/33 (0%)
Hepatic enzyme increased	2/25 (8%)		0/33 (0%)
Lymphocyte count decreased	0/25 (0%)		2/33 (6.1%)
White blood cell count decreased	3/25 (12%)		0/33 (0%)
Metabolism and nutrition disorders
Dehydration	2/25 (8%)		2/33 (6.1%)
Diabetes mellitus	2/25 (8%)		5/33 (15.2%)
Fluid overload	3/25 (12%)		1/33 (3%)
Hyperglycaemia	3/25 (12%)		5/33 (15.2%)
Hyperkalaemia	1/25 (4%)		11/33 (33.3%)
Hypocalcaemia	2/25 (8%)		3/33 (9.1%)
Hypoglycaemia	0/25 (0%)		2/33 (6.1%)
Hypokalaemia	7/25 (28%)		3/33 (9.1%)
Hypomagnesaemia	2/25 (8%)		8/33 (24.2%)
Hyponatraemia	0/25 (0%)		2/33 (6.1%)
Hypophosphataemia	9/25 (36%)		8/33 (24.2%)
Metabolic acidosis	4/25 (16%)		3/33 (9.1%)
Vitamin D deficiency	0/25 (0%)		2/33 (6.1%)
Musculoskeletal and connective tissue disorders
Arthralgia	6/25 (24%)		1/33 (3%)
Back pain	1/25 (4%)		2/33 (6.1%)
Flank pain	2/25 (8%)		0/33 (0%)
Muscle spasms	0/25 (0%)		3/33 (9.1%)
Myalgia	0/25 (0%)		2/33 (6.1%)
Pain in extremity	1/25 (4%)		2/33 (6.1%)
Nervous system disorders
Dizziness	2/25 (8%)		4/33 (12.1%)
Headache	5/25 (20%)		7/33 (21.2%)
Hypoaesthesia	1/25 (4%)		3/33 (9.1%)
Paraesthesia	0/25 (0%)		3/33 (9.1%)
Tremor	0/25 (0%)		6/33 (18.2%)
Psychiatric disorders
Anxiety	2/25 (8%)		1/33 (3%)
Insomnia	3/25 (12%)		5/33 (15.2%)
Renal and urinary disorders
Dysuria	3/25 (12%)		4/33 (12.1%)
Haematuria	1/25 (4%)		5/33 (15.2%)
Perinephric collection	0/25 (0%)		4/33 (12.1%)
Proteinuria	4/25 (16%)		2/33 (6.1%)
Renal impairment	1/25 (4%)		2/33 (6.1%)
Renal tubular necrosis	1/25 (4%)		3/33 (9.1%)
Urinary retention	1/25 (4%)		2/33 (6.1%)
Respiratory, thoracic and mediastinal disorders
Cough	2/25 (8%)		2/33 (6.1%)
Dyspnoea	2/25 (8%)		2/33 (6.1%)
Epistaxis	3/25 (12%)		0/33 (0%)
Nasal congestion	2/25 (8%)		2/33 (6.1%)
Oropharyngeal pain	1/25 (4%)		5/33 (15.2%)
Skin and subcutaneous tissue disorders
Pruritus	0/25 (0%)		2/33 (6.1%)
Seborrhoeic dermatitis	2/25 (8%)		0/33 (0%)
Vascular disorders
Hypertension	6/25 (24%)		8/33 (24.2%)
Hypotension	0/25 (0%)		2/33 (6.1%)
Orthostatic hypotension	2/25 (8%)		0/33 (0%)

Limitations/Caveats

One participant with BPAR had been randomized to the BELA+EVL group, but had then mistakenly been treated with TAC+MMF beginning on Day 1 and continuing through the entire 2-year study period. Due to this, time to CSBPAR was performed using this inaccurate population, therefore inaccurate data is not presented.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.