A Phase II Study of Belatacept (BMS-224818) With a Steroid-free Regimen in Subjects Undergoing Kidney Transplantation

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00455013
First received: March 30, 2007
Last updated: May 27, 2014
Last verified: May 2014
Results First Received: July 16, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Disorder Related to Renal Transplantation
Interventions: Drug: Thymoglobulin
Drug: Belatacept
Drug: Sirolimus
Drug: Tacrolimus
Drug: Mycophenolate Mofetil (MMF)

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Epstein-Barr virus positive recipients of renal allograft from living or deceased donor. Excluded if panel reactive antibodies greater than, equal to (>=) 50 % or prior graft loss due to acute rejection. 93 participants randomized; 89 transplanted/treated: (1) fever on the day of surgery, (1) problem with allograft, and (2) withdrawal of consent.

Reporting Groups
  Description
Belatacept, Mycophenolate Mofetil (MMF) Thymoglobulin 1.5mg/kg for 4 days plus 4 corresponding doses of corticosteroids; intravenous infusion (IV) belatacept: 10 milligram per kilogram of weight (mg/kg) Day 1 (day of transplant) and Day 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 (mycophenolate mofetil) 1g twice daily(BID). Participants were allowed to switch from MMF to sirolimus. Background immunosuppressive medications: methylprednisolone administered as 500, 250, 125, and 60 mg IV on Days 1, 2, 3, 4; thymoglobulin 1.5 mg/kg IV infusion on Days 1 (day of transplant), 2, 3, 4, up to maximum dose of 6 mg/kg.
Belatacept, Sirolimus Thymoglobulin 1.5mg/kg for 4 days plus 4 corresponding doses of corticosteroids; 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 Month 12; sirolimus 5 mg/day on Day 1 and continued through Day 2, dosing to be adjusted to keep pre-dose C0 (concentration at time zero after administration) levels at 7-12 nanograms per milliliter (ng/mL) for first 6 months, followed by 5 - 10 ng/mL until 12 months. Participants were allowed to switch from sirolimus to MMF. Background immunosuppressive medications: methylprednisolone was administered as 500, 250, 125, and 60 mg IV on Days 1, 2, 3, 4, up to maximum dose of 6 mg/kg.
Tacrolimus, MMF Comparator regimen: thymoglobulin 1.5mg/kg for 4 days plus 4 corresponding doses of corticosteroids; 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 1g BID. Background immunosuppressive medications: methylprednisolone administered as 500, 250, 125, and 60 mg IV on Days 1, 2, 3, 4; thymoglobulin 1.5 mg/kg IV infusion on Days 1, 2, 3, 4 up to maximum dose of 6 mg/kg.

Participant Flow for 2 periods

Period 1:   Short Term Period
    Belatacept, Mycophenolate Mofetil (MMF)     Belatacept, Sirolimus     Tacrolimus, MMF  
STARTED     33 [1]   26 [2]   30 [3]
COMPLETED     27 [4]   21 [5]   28 [6]
NOT COMPLETED     6     5     2  
Adverse Event                 2                 5                 0  
Withdrawal by Subject                 0                 0                 1  
Lack of Efficacy                 4                 0                 0  
Unspecified                 0                 0                 1  
[1] 35 randomized, 33 transplanted and treated.
[2] 27 randomized, 26 transplanted and treated.
[3] 31 randomized, 30 transplanted and treated
[4] 5 discontinued belatacept by Month 6 (1 more by Month 12), 2 switched from MMF to sirolimus.
[5] 5 discontinued belatacept by Month 6; 10 additional switched from sirolimus to MMF.
[6] 1 discontinued tacrolimus by Month 6 and 2 discontinued by Month 12 (1 more by Month 12)

Period 2:   Long Term Extension (LTE)
    Belatacept, Mycophenolate Mofetil (MMF)     Belatacept, Sirolimus     Tacrolimus, MMF  
STARTED     27     19 [1]   27 [2]
COMPLETED     25     16     20  
NOT COMPLETED     2     3     7  
Adverse Event                 0                 1                 1  
Withdrawal by Subject                 1                 0                 1  
Death                 1                 1                 0  
No longer met criteria                 0                 0                 1  
Subject Request or refused                 0                 0                 3  
Poor non-compliance                 0                 1                 0  
non-specified                 0                 0                 1  
[1] 2 Participants chose not to enter the LTE.
[2] 1 Participant chose not to enter the LTE.



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants who received transplant and were treated with drug were analyzed up to Month 12 post transplant.

Reporting Groups
  Description
Belatacept, Mycophenolate Mofetil (MMF) Thymoglobulin 1.5mg/kg for 4 days plus 4 corresponding doses of corticosteroids; 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 Month 12; MMF 1g BID. Participants were allowed to switch from MMF to sirolimus.
Belatacept, Sirolimus Thymoglobulin 1.5mg/kg for 4 days plus 4 corresponding doses of corticosteroids; 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 Month 12; sirolimus 5 mg/day on Day 1 and continued through Day 2, dosing to be adjusted to keep pre-dose C0 (concentration at time zero after administration) levels at 7-12 ng/mL for first 6 months, followed by 5 - 10 ng/mL until Month 12. Participants were allowed to switch from sirolimus to MMF.
Tacrolimus, MMF Comparator regimen: thymoglobulin 1.5mg/kg for 4 days plus 4 corresponding doses of corticosteroids; 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.
Total Total of all reporting groups

Baseline Measures
    Belatacept, Mycophenolate Mofetil (MMF)     Belatacept, Sirolimus     Tacrolimus, MMF     Total  
Number of Participants  
[units: participants]
  33     26     30     89  
Age  
[units: participants]
       
<=18 years     0     0     0     0  
Between 18 and 65 years     33     24     26     83  
>=65 years     0     2     4     6  
Age  
[units: years]
Mean ± Standard Deviation
  49.2  ± 11.1     52.7  ± 10.8     53.6  ± 13.2     51.7  ± 11.8  
Gender  
[units: participants]
       
Female     8     6     8     22  
Male     25     20     22     67  
Region of Enrollment  
[units: participants]
       
North America     22     16     20     58  
Europe     11     10     10     31  



  Outcome Measures
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1.  Primary:   Number of Participants With Acute Rejection (AR) of Transplant up to 6 Months Post Transplantation - Intent to Treat (ITT) Population   [ Time Frame: Day 1 to Month 6 post-transplantation ]

2.  Secondary:   Number of Participants With Acute Rejection of Transplant up to Month 12 Post Transplantation - Intent to Treat Population   [ Time Frame: Day 1 to Month 12 post transplantation ]

3.  Secondary:   Number of Participants With Graft Loss or Death up to Month 6 and Month 12 Post Transplantation - Intent to Treat Population   [ Time Frame: Day 1 to Month 6 and Month 12 post transplantation ]

4.  Secondary:   Number of Participants With Composite of Death, Graft Loss and Acute Rejection up to Month 6 - Intent to Treat Population   [ Time Frame: Day 1 up to Month 6 ]

5.  Secondary:   Number of Participants With Composite of Death, Graft Loss and Acute Rejection up to Month 12 - Intent to Treat Population   [ Time Frame: Day 1 up to Month 12 ]

6.  Secondary:   Number of Participants With Delayed Graft Function - Intent to Treat Population   [ Time Frame: From Day 1 up to and including Day 8 post transplantation ]

7.  Secondary:   Number of Participants With New Onset Diabetes Mellitus From Baseline to Month 12 Post Transplantation - Intent to Treat Population   [ Time Frame: Baseline to Month 12 ]

8.  Secondary:   Number of Participants Who Used Anti-hypertension Medications at Baseline and at 12 Months Post Transplantation - Intent to Treat Population   [ Time Frame: Baseline and Month 12 ]

9.  Secondary:   Mean Systolic, Diastolic and Arterial Blood Pressure at Baseline and Month 12 - Intent to Treat Population   [ Time Frame: Baseline and 12 months post transplantation ]

10.  Secondary:   Number of Participants Using Antihyperlipidemic Medications at Month 12 - Intent to Treat Population   [ Time Frame: Month 12 ]

11.  Secondary:   Mean Change From Baseline (BL) to Month 12 Post Transplantation in Lipid Values - Intent to Treat Population   [ Time Frame: Baseline to Month 12 ]

12.  Secondary:   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   [ Time Frame: Months 3, 6 and 12 post transplantation ]

13.  Secondary:   Number of Corticosteroid-free Participants at 6 and 12 Months Post Transplantation - Intent to Treat Population   [ Time Frame: Day 1 through Month 12 ]

14.  Secondary:   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   [ Time Frame: Day 1 to Month 12 post transplantation ]

15.  Secondary:   Number of Participants With Acute Rejection of Transplant up to End of Month 48 Post Transplantation - Intent to Treat Population in Long Term Extension   [ Time Frame: End of Month 12 to end of Month 48 Post Transplantation ]

16.  Secondary:   Number of Participants With Graft Loss or Death at Months 24, 36, 48 Post Transplantation - Intent to Treat Population in Long Term Extension   [ Time Frame: End of Month 12 to end of Long Term Extension (Year 4) ]

17.  Secondary:   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   [ Time Frame: Months 24, 36 and 48 post transplantation ]

18.  Secondary:   Number of Corticosteroid-free Participants at Months 24, 36, 48 Post Transplantation - Intent to Treat Population in Long Term Extension   [ Time Frame: End of Month 12 to end of Long Term Extension (Year 4) ]

19.  Secondary:   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   [ Time Frame: Months 24, 36, 48 ]

20.  Secondary:   Number of Participants Who Switched Between MMF and Sirolimus During Long Term Extension up to Study Completion   [ Time Frame: End of Month 12 to end of Study (Month 48) ]


  Serious Adverse Events


  Other Adverse Events
  Hide Other Adverse Events

Time Frame From Day 1 to end of 48 Months post transplantation and study closure
Additional Description Total population of randomized participants in both short term period and long term extension.

Frequency Threshold
Threshold above which other adverse events are reported   5%  

Reporting Groups
  Description
Belatacept - MMF No text entered.
Belatacept - SIRO No text entered.
Tacrolimus - MMF No text entered.

Other Adverse Events
    Belatacept - MMF     Belatacept - SIRO     Tacrolimus - MMF  
Total, other (not including serious) adverse events        
# participants affected / at risk     33/33     26/26     30/30  
Blood and lymphatic system disorders        
Neutropenia † 1      
# participants affected / at risk     4/33 (12.12%)     4/26 (15.38%)     3/30 (10.00%)  
Thrombocytopenia † 1      
# participants affected / at risk     3/33 (9.09%)     1/26 (3.85%)     2/30 (6.67%)  
Leukocytosis † 1      
# participants affected / at risk     2/33 (6.06%)     1/26 (3.85%)     0/30 (0.00%)  
Anaemia † 1      
# participants affected / at risk     20/33 (60.61%)     18/26 (69.23%)     14/30 (46.67%)  
Leukopenia † 1      
# participants affected / at risk     18/33 (54.55%)     12/26 (46.15%)     15/30 (50.00%)  
Lymphopenia † 1      
# participants affected / at risk     3/33 (9.09%)     1/26 (3.85%)     2/30 (6.67%)  
Polycythaemia † 1      
# participants affected / at risk     2/33 (6.06%)     0/26 (0.00%)     2/30 (6.67%)  
Iron deficiency anaemia † 1      
# participants affected / at risk     2/33 (6.06%)     1/26 (3.85%)     1/30 (3.33%)  
Cardiac disorders        
Tachycardia † 1      
# participants affected / at risk     5/33 (15.15%)     5/26 (19.23%)     2/30 (6.67%)  
Ear and labyrinth disorders        
Ear pain † 1      
# participants affected / at risk     2/33 (6.06%)     0/26 (0.00%)     2/30 (6.67%)  
Motion sickness † 1      
# participants affected / at risk     1/33 (3.03%)     3/26 (11.54%)     0/30 (0.00%)  
Endocrine disorders        
Hyperparathyroidism † 1      
# participants affected / at risk     3/33 (9.09%)     2/26 (7.69%)     0/30 (0.00%)  
Hyperparathyroidism tertiary † 1      
# participants affected / at risk     1/33 (3.03%)     0/26 (0.00%)     2/30 (6.67%)  
Parathyroid gland enlargement † 1      
# participants affected / at risk     0/33 (0.00%)     0/26 (0.00%)     2/30 (6.67%)  
Eye disorders        
Conjunctivitis † 1      
# participants affected / at risk     2/33 (6.06%)     1/26 (3.85%)     0/30 (0.00%)  
Vision blurred † 1      
# participants affected / at risk     2/33 (6.06%)     1/26 (3.85%)     5/30 (16.67%)  
Cataract † 1      
# participants affected / at risk     0/33 (0.00%)     2/26 (7.69%)     3/30 (10.00%)  
Dry eye † 1      
# participants affected / at risk     0/33 (0.00%)     1/26 (3.85%)     2/30 (6.67%)  
Gastrointestinal disorders        
Abdominal pain lower † 1      
# participants affected / at risk     6/33 (18.18%)     2/26 (7.69%)     2/30 (6.67%)  
Aphthous stomatitis † 1      
# participants affected / at risk     4/33 (12.12%)     9/26 (34.62%)     0/30 (0.00%)  
Constipation † 1      
# participants affected / at risk     16/33 (48.48%)     11/26 (42.31%)     12/30 (40.00%)  
Diarrhoea † 1      
# participants affected / at risk     13/33 (39.39%)     17/26 (65.38%)     21/30 (70.00%)  
Haematochezia † 1      
# participants affected / at risk     4/33 (12.12%)     0/26 (0.00%)     0/30 (0.00%)  
Vomiting † 1      
# participants affected / at risk     11/33 (33.33%)     5/26 (19.23%)     8/30 (26.67%)  
Toothache † 1      
# participants affected / at risk     2/33 (6.06%)     3/26 (11.54%)     1/30 (3.33%)  
Abdominal discomfort † 1      
# participants affected / at risk     3/33 (9.09%)     3/26 (11.54%)     1/30 (3.33%)  
Abdominal pain † 1      
# participants affected / at risk     5/33 (15.15%)     5/26 (19.23%)     7/30 (23.33%)  
Mouth ulceration † 1      
# participants affected / at risk     3/33 (9.09%)     8/26 (30.77%)     0/30 (0.00%)  
Dry mouth † 1      
# participants affected / at risk     0/33 (0.00%)     3/26 (11.54%)     2/30 (6.67%)  
Dysphagia † 1      
# participants affected / at risk     1/33 (3.03%)     3/26 (11.54%)     0/30 (0.00%)  
Stomatitis † 1      
# participants affected / at risk     2/33 (6.06%)     4/26 (15.38%)     1/30 (3.33%)  
Abdominal pain upper † 1      
# participants affected / at risk     1/33 (3.03%)     1/26 (3.85%)     2/30 (6.67%)  
Flatulence † 1      
# participants affected / at risk     4/33 (12.12%)     3/26 (11.54%)     1/30 (3.33%)  
Food poisoning † 1      
# participants affected / at risk     0/33 (0.00%)     2/26 (7.69%)     0/30 (0.00%)  
Odynophagia † 1      
# participants affected / at risk     1/33 (3.03%)     3/26 (11.54%)     0/30 (0.00%)  
Abdominal tenderness † 1      
# participants affected / at risk     1/33 (3.03%)     2/26 (7.69%)     4/30 (13.33%)  
Gastrooesophageal reflux disease † 1      
# participants affected / at risk     4/33 (12.12%)     1/26 (3.85%)     1/30 (3.33%)  
Abdominal distension † 1      
# participants affected / at risk     2/33 (6.06%)     4/26 (15.38%)     4/30 (13.33%)  
Dyspepsia † 1      
# participants affected / at risk     2/33 (6.06%)     5/26 (19.23%)     4/30 (13.33%)  
Nausea † 1      
# participants affected / at risk     14/33 (42.42%)     7/26 (26.92%)     12/30 (40.00%)  
Retching † 1      
# participants affected / at risk     0/33 (0.00%)     0/26 (0.00%)     2/30 (6.67%)  
General disorders        
Chest pain † 1      
# participants affected / at risk     2/33 (6.06%)     0/26 (0.00%)     1/30 (3.33%)  
Face oedema † 1      
# participants affected / at risk     2/33 (6.06%)     2/26 (7.69%)     3/30 (10.00%)  
Asthenia † 1      
# participants affected / at risk     10/33 (30.30%)     8/26 (30.77%)     6/30 (20.00%)  
Pyrexia † 1      
# participants affected / at risk     16/33 (48.48%)     17/26 (65.38%)     15/30 (50.00%)  
Chills † 1      
# participants affected / at risk     6/33 (18.18%)     3/26 (11.54%)     1/30 (3.33%)  
Pain † 1      
# participants affected / at risk     1/33 (3.03%)     4/26 (15.38%)     5/30 (16.67%)  
Malaise † 1      
# participants affected / at risk     2/33 (6.06%)     1/26 (3.85%)     1/30 (3.33%)  
Oedema peripheral † 1      
# participants affected / at risk     14/33 (42.42%)     15/26 (57.69%)     10/30 (33.33%)  
Fatigue † 1      
# participants affected / at risk     7/33 (21.21%)     8/26 (30.77%)     9/30 (30.00%)  
Oedema † 1      
# participants affected / at risk     5/33 (15.15%)     3/26 (11.54%)     3/30 (10.00%)  
Generalised oedema † 1      
# participants affected / at risk     3/33 (9.09%)     4/26 (15.38%)     5/30 (16.67%)  
Immune system disorders        
Seasonal allergy † 1      
# participants affected / at risk     3/33 (9.09%)     1/26 (3.85%)     1/30 (3.33%)  
Infections and infestations        
Escherichia urinary tract infection † 1      
# participants affected / at risk     0/33 (0.00%)     1/26 (3.85%)     2/30 (6.67%)  
Gastroenteritis viral † 1      
# participants affected / at risk     0/33 (0.00%)     3/26 (11.54%)     1/30 (3.33%)  
Tooth infection † 1      
# participants affected / at risk     3/33 (9.09%)     1/26 (3.85%)     1/30 (3.33%)  
Localised infection † 1      
# participants affected / at risk     3/33 (9.09%)     0/26 (0.00%)     0/30 (0.00%)  
Nasopharyngitis † 1      
# participants affected / at risk     8/33 (24.24%)     7/26 (26.92%)     4/30 (13.33%)  
Sinusitis † 1      
# participants affected / at risk     6/33 (18.18%)     4/26 (15.38%)     4/30 (13.33%)  
Bronchitis † 1      
# participants affected / at risk     4/33 (12.12%)     1/26 (3.85%)     0/30 (0.00%)  
Fungal infection † 1      
# participants affected / at risk     0/33 (0.00%)     0/26 (0.00%)     2/30 (6.67%)  
Influenza † 1      
# participants affected / at risk     3/33 (9.09%)     2/26 (7.69%)     1/30 (3.33%)  
Oral candidiasis † 1      
# participants affected / at risk     2/33 (6.06%)     3/26 (11.54%)     0/30 (0.00%)  
Oral herpes † 1      
# participants affected / at risk     4/33 (12.12%)     1/26 (3.85%)     0/30 (0.00%)  
Pneumonia † 1      
# participants affected / at risk     2/33 (6.06%)     2/26 (7.69%)     1/30 (3.33%)  
Upper respiratory tract infection † 1      
# participants affected / at risk     4/33 (12.12%)     5/26 (19.23%)     2/30 (6.67%)  
Urinary tract infection † 1      
# participants affected / at risk     14/33 (42.42%)     8/26 (30.77%)     10/30 (33.33%)  
Furuncle † 1      
# participants affected / at risk     1/33 (3.03%)     2/26 (7.69%)     0/30 (0.00%)  
Herpes zoster † 1      
# participants affected / at risk     0/33 (0.00%)     2/26 (7.69%)     1/30 (3.33%)  
Vaginal infection † 1      
# participants affected / at risk     0/33 (0.00%)     0/26 (0.00%)     2/30 (6.67%)  
BK virus infection † 1      
# participants affected / at risk     2/33 (6.06%)     1/26 (3.85%)     1/30 (3.33%)  
Ear infection † 1      
# participants affected / at risk     1/33 (3.03%)     2/26 (7.69%)     3/30 (10.00%)  
Cellulitis † 1      
# participants affected / at risk     2/33 (6.06%)     2/26 (7.69%)     0/30 (0.00%)  
Cytomegalovirus infection † 1      
# participants affected / at risk     0/33 (0.00%)     2/26 (7.69%)     0/30 (0.00%)  
Gastroenteritis † 1      
# participants affected / at risk     2/33 (6.06%)     2/26 (7.69%)     0/30 (0.00%)  
Pharyngitis † 1      
# participants affected / at risk     0/33 (0.00%)     2/26 (7.69%)     0/30 (0.00%)  
Injury, poisoning and procedural complications        
Graft dysfunction † 1      
# participants affected / at risk     0/33 (0.00%)     1/26 (3.85%)     4/30 (13.33%)  
Muscle strain † 1      
# participants affected / at risk     0/33 (0.00%)     2/26 (7.69%)     0/30 (0.00%)  
Contusion † 1      
# participants affected / at risk     0/33 (0.00%)     1/26 (3.85%)     2/30 (6.67%)  
Laceration † 1      
# participants affected / at risk     1/33 (3.03%)     2/26 (7.69%)     3/30 (10.00%)  
Limb injury † 1      
# participants affected / at risk     0/33 (0.00%)     2/26 (7.69%)     0/30 (0.00%)  
Procedural pain † 1      
# participants affected / at risk     19/33 (57.58%)     11/26 (42.31%)     13/30 (43.33%)  
Wound † 1      
# participants affected / at risk     1/33 (3.03%)     2/26 (7.69%)     0/30 (0.00%)  
Wound dehiscence † 1      
# participants affected / at risk     0/33 (0.00%)     0/26 (0.00%)     2/30 (6.67%)  
Incision site haemorrhage † 1      
# participants affected / at risk     2/33 (6.06%)     0/26 (0.00%)     3/30 (10.00%)  
Fall † 1      
# participants affected / at risk     3/33 (9.09%)     2/26 (7.69%)     2/30 (6.67%)  
Post procedural discharge † 1      
# participants affected / at risk     0/33 (0.00%)     1/26 (3.85%)     2/30 (6.67%)  
Incision site erythema † 1      
# participants affected / at risk     2/33 (6.06%)     2/26 (7.69%)     4/30 (13.33%)  
Incision site pain † 1      
# participants affected / at risk     4/33 (12.12%)     5/26 (19.23%)     7/30 (23.33%)  
Investigations        
Blood glucose increased † 1      
# participants affected / at risk     0/33 (0.00%)     0/26 (0.00%)     2/30 (6.67%)  
Blood iron decreased † 1      
# participants affected / at risk     1/33 (3.03%)     2/26 (7.69%)     0/30 (0.00%)  
Blood urine present † 1      
# participants affected / at risk     2/33 (6.06%)     0/26 (0.00%)     0/30 (0.00%)  
Heart rate irregular † 1      
# participants affected / at risk     0/33 (0.00%)     0/26 (0.00%)     2/30 (6.67%)  
Urine output decreased † 1      
# participants affected / at risk     2/33 (6.06%)     2/26 (7.69%)     3/30 (10.00%)  
Weight decreased † 1      
# participants affected / at risk     6/33 (18.18%)     6/26 (23.08%)     4/30 (13.33%)  
Blood pressure increased † 1      
# participants affected / at risk     3/33 (9.09%)     0/26 (0.00%)     6/30 (20.00%)  
White blood cell count decreased † 1      
# participants affected / at risk     2/33 (6.06%)     2/26 (7.69%)     3/30 (10.00%)  
White blood cell count increased † 1      
# participants affected / at risk     2/33 (6.06%)     0/26 (0.00%)     1/30 (3.33%)  
Blood creatinine increased † 1      
# participants affected / at risk     6/33 (18.18%)     3/26 (11.54%)     7/30 (23.33%)  
Prostatic specific antigen increased † 1      
# participants affected / at risk     1/33 (3.03%)     0/26 (0.00%)     2/30 (6.67%)  
Renal bruit † 1      
# participants affected / at risk     1/33 (3.03%)     0/26 (0.00%)     2/30 (6.67%)  
Breath sounds abnormal † 1      
# participants affected / at risk     5/33 (15.15%)     2/26 (7.69%)     5/30 (16.67%)  
Weight increased † 1      
# participants affected / at risk     6/33 (18.18%)     4/26 (15.38%)     7/30 (23.33%)  
Blood magnesium decreased † 1      
# participants affected / at risk     0/33 (0.00%)     0/26 (0.00%)     2/30 (6.67%)  
Haemoglobin decreased † 1      
# participants affected / at risk     1/33 (3.03%)     2/26 (7.69%)     0/30 (0.00%)  
Metabolism and nutrition disorders        
Electrolyte imbalance † 1      
# participants affected / at risk     3/33 (9.09%)     1/26 (3.85%)     1/30 (3.33%)  
Fluid retention † 1      
# participants affected / at risk     2/33 (6.06%)     2/26 (7.69%)     2/30 (6.67%)  
Hyponatraemia † 1      
# participants affected / at risk     2/33 (6.06%)     1/26 (3.85%)     1/30 (3.33%)  
Metabolic acidosis † 1      
# participants affected / at risk     2/33 (6.06%)     4/26 (15.38%)     4/30 (13.33%)  
Hyperuricaemia † 1      
# participants affected / at risk     3/33 (9.09%)     0/26 (0.00%)     1/30 (3.33%)  
Hypophosphataemia † 1      
# participants affected / at risk     12/33 (36.36%)     6/26 (23.08%)     5/30 (16.67%)  
Vitamin D deficiency † 1      
# participants affected / at risk     3/33 (9.09%)     1/26 (3.85%)     2/30 (6.67%)  
Decreased appetite † 1      
# participants affected / at risk     2/33 (6.06%)     2/26 (7.69%)     4/30 (13.33%)  
Dyslipidaemia † 1      
# participants affected / at risk     7/33 (21.21%)     3/26 (11.54%)     2/30 (6.67%)  
Hypercholesterolaemia † 1      
# participants affected / at risk     3/33 (9.09%)     5/26 (19.23%)     1/30 (3.33%)  
Hyperglycaemia † 1      
# participants affected / at risk     4/33 (12.12%)     4/26 (15.38%)     6/30 (20.00%)  
Hypoglycaemia † 1      
# participants affected / at risk     6/33 (18.18%)     2/26 (7.69%)     5/30 (16.67%)  
Hypomagnesaemia † 1      
# participants affected / at risk     2/33 (6.06%)     2/26 (7.69%)     5/30 (16.67%)  
Hyperlipidaemia † 1      
# participants affected / at risk     1/33 (3.03%)     2/26 (7.69%)     3/30 (10.00%)  
Diabetes mellitus † 1      
# participants affected / at risk     3/33 (9.09%)     0/26 (0.00%)     2/30 (6.67%)  
Hyperkalaemia † 1      
# participants affected / at risk     9/33 (27.27%)     6/26 (23.08%)     9/30 (30.00%)  
Dehydration † 1      
# participants affected / at risk     5/33 (15.15%)     4/26 (15.38%)     5/30 (16.67%)  
Hypercalcaemia † 1      
# participants affected / at risk     6/33 (18.18%)     2/26 (7.69%)     2/30 (6.67%)  
Hypertriglyceridaemia † 1      
# participants affected / at risk     1/33 (3.03%)     0/26 (0.00%)     2/30 (6.67%)  
Hypokalaemia † 1      
# participants affected / at risk     8/33 (24.24%)     8/26 (30.77%)     4/30 (13.33%)  
Hypocalcaemia † 1      
# participants affected / at risk     2/33 (6.06%)     4/26 (15.38%)     4/30 (13.33%)  
Hypovolaemia † 1      
# participants affected / at risk     2/33 (6.06%)     2/26 (7.69%)     0/30 (0.00%)  
Musculoskeletal and connective tissue disorders        
Joint swelling † 1      
# participants affected / at risk     4/33 (12.12%)     2/26 (7.69%)     0/30 (0.00%)  
Neck pain † 1      
# participants affected / at risk     2/33 (6.06%)     0/26 (0.00%)     3/30 (10.00%)  
Back pain † 1      
# participants affected / at risk     8/33 (24.24%)     8/26 (30.77%)     4/30 (13.33%)  
Joint effusion † 1      
# participants affected / at risk     0/33 (0.00%)     2/26 (7.69%)     0/30 (0.00%)  
Muscle spasms † 1      
# participants affected / at risk     4/33 (12.12%)     0/26 (0.00%)     3/30 (10.00%)  
Musculoskeletal discomfort † 1      
# participants affected / at risk     2/33 (6.06%)     0/26 (0.00%)     0/30 (0.00%)  
Musculoskeletal pain † 1      
# participants affected / at risk     0/33 (0.00%)     1/26 (3.85%)     4/30 (13.33%)  
Osteopenia † 1      
# participants affected / at risk     2/33 (6.06%)     0/26 (0.00%)     1/30 (3.33%)  
Pain in extremity † 1      
# participants affected / at risk     9/33 (27.27%)     7/26 (26.92%)     5/30 (16.67%)  
Tendon pain † 1      
# participants affected / at risk     0/33 (0.00%)     2/26 (7.69%)     0/30 (0.00%)  
Flank pain † 1      
# participants affected / at risk     0/33 (0.00%)     0/26 (0.00%)     2/30 (6.67%)  
Joint range of motion decreased † 1      
# participants affected / at risk     0/33 (0.00%)     2/26 (7.69%)     0/30 (0.00%)  
Muscular weakness † 1      
# participants affected / at risk     2/33 (6.06%)     1/26 (3.85%)     2/30 (6.67%)  
Plantar fasciitis † 1      
# participants affected / at risk     2/33 (6.06%)     0/26 (0.00%)     0/30 (0.00%)  
Myalgia † 1      
# participants affected / at risk     5/33 (15.15%)     0/26 (0.00%)     2/30 (6.67%)  
Arthralgia † 1      
# participants affected / at risk     5/33 (15.15%)     9/26 (34.62%)     3/30 (10.00%)  
Arthritis † 1      
# participants affected / at risk     1/33 (3.03%)     1/26 (3.85%)     2/30 (6.67%)  
Osteoporosis † 1      
# participants affected / at risk     2/33 (6.06%)     0/26 (0.00%)     1/30 (3.33%)  
Neoplasms benign, malignant and unspecified (incl cysts and polyps)        
Seborrhoeic keratosis † 1      
# participants affected / at risk     0/33 (0.00%)     0/26 (0.00%)     3/30 (10.00%)  
Skin papilloma † 1      
# participants affected / at risk     1/33 (3.03%)     0/26 (0.00%)     2/30 (6.67%)  
Nervous system disorders        
Dizziness † 1      
# participants affected / at risk     5/33 (15.15%)     4/26 (15.38%)     6/30 (20.00%)  
Hypoaesthesia † 1      
# participants affected / at risk     4/33 (12.12%)     2/26 (7.69%)     3/30 (10.00%)  
Amnesia † 1      
# participants affected / at risk     2/33 (6.06%)     1/26 (3.85%)     3/30 (10.00%)  
Disturbance in attention † 1      
# participants affected / at risk     2/33 (6.06%)     0/26 (0.00%)     0/30 (0.00%)  
Headache † 1      
# participants affected / at risk     7/33 (21.21%)     9/26 (34.62%)     9/30 (30.00%)  
Sinus headache † 1      
# participants affected / at risk     3/33 (9.09%)     0/26 (0.00%)     1/30 (3.33%)  
Lethargy † 1      
# participants affected / at risk     2/33 (6.06%)     0/26 (0.00%)     2/30 (6.67%)  
Carpal tunnel syndrome † 1      
# participants affected / at risk     0/33 (0.00%)     1/26 (3.85%)     2/30 (6.67%)  
Dysgeusia † 1      
# participants affected / at risk     0/33 (0.00%)     1/26 (3.85%)     3/30 (10.00%)  
Paraesthesia † 1      
# participants affected / at risk     4/33 (12.12%)     3/26 (11.54%)     4/30 (13.33%)  
Memory impairment † 1      
# participants affected / at risk     2/33 (6.06%)     0/26 (0.00%)     0/30 (0.00%)  
Neuropathy peripheral † 1      
# participants affected / at risk     2/33 (6.06%)     1/26 (3.85%)     2/30 (6.67%)  
Tremor † 1      
# participants affected / at risk     1/33 (3.03%)     0/26 (0.00%)     9/30 (30.00%)  
Psychiatric disorders        
Confusional state † 1      
# participants affected / at risk     2/33 (6.06%)     1/26 (3.85%)     1/30 (3.33%)  
Insomnia † 1      
# participants affected / at risk     7/33 (21.21%)     5/26 (19.23%)     7/30 (23.33%)  
Depression † 1      
# participants affected / at risk     3/33 (9.09%)     3/26 (11.54%)     1/30 (3.33%)  
Anxiety † 1      
# participants affected / at risk     4/33 (12.12%)     6/26 (23.08%)     3/30 (10.00%)  
Sleep disorder † 1      
# participants affected / at risk     1/33 (3.03%)     0/26 (0.00%)     2/30 (6.67%)  
Renal and urinary disorders        
Renal tubular necrosis † 1      
# participants affected / at risk     3/33 (9.09%)     0/26 (0.00%)     1/30 (3.33%)  
Urinary incontinence † 1      
# participants affected / at risk     0/33 (0.00%)     2/26 (7.69%)     1/30 (3.33%)  
Nocturia † 1      
# participants affected / at risk     1/33 (3.03%)     0/26 (0.00%)     2/30 (6.67%)  
Renal impairment † 1      
# participants affected / at risk     0/33 (0.00%)     2/26 (7.69%)     4/30 (13.33%)  
Ureteric dilatation † 1      
# participants affected / at risk     0/33 (0.00%)     0/26 (0.00%)     2/30 (6.67%)  
Dysuria † 1      
# participants affected / at risk     4/33 (12.12%)     1/26 (3.85%)     4/30 (13.33%)  
Renal disorder † 1      
# participants affected / at risk     1/33 (3.03%)     0/26 (0.00%)     2/30 (6.67%)  
Micturition urgency † 1      
# participants affected / at risk     2/33 (6.06%)     1/26 (3.85%)     0/30 (0.00%)  
Proteinuria † 1      
# participants affected / at risk     6/33 (18.18%)     2/26 (7.69%)     0/30 (0.00%)  
Bladder spasm † 1      
# participants affected / at risk     4/33 (12.12%)     1/26 (3.85%)     1/30 (3.33%)  
Urethral stenosis † 1      
# participants affected / at risk     1/33 (3.03%)     2/26 (7.69%)     0/30 (0.00%)  
Haematuria † 1      
# participants affected / at risk     9/33 (27.27%)     11/26 (42.31%)     6/30 (20.00%)  
Pollakiuria † 1      
# participants affected / at risk     3/33 (9.09%)     1/26 (3.85%)     1/30 (3.33%)  
Urinary retention † 1      
# participants affected / at risk     2/33 (6.06%)     1/26 (3.85%)     3/30 (10.00%)  
Reproductive system and breast disorders        
Scrotal oedema † 1      
# participants affected / at risk     2/33 (6.06%)     2/26 (7.69%)     1/30 (3.33%)  
Testicular pain † 1      
# participants affected / at risk     1/33 (3.03%)     0/26 (0.00%)     2/30 (6.67%)  
Respiratory, thoracic and mediastinal disorders        
Pleural effusion † 1      
# participants affected / at risk     0/33 (0.00%)     0/26 (0.00%)     2/30 (6.67%)  
Rhinorrhoea † 1      
# participants affected / at risk     2/33 (6.06%)     1/26 (3.85%)     2/30 (6.67%)  
Dyspnoea exertional † 1      
# participants affected / at risk     2/33 (6.06%)     1/26 (3.85%)     3/30 (10.00%)  
Sleep apnoea syndrome † 1      
# participants affected / at risk     2/33 (6.06%)     0/26 (0.00%)     0/30 (0.00%)  
Wheezing † 1      
# participants affected / at risk     0/33 (0.00%)     0/26 (0.00%)     2/30 (6.67%)  
Hypoxia † 1      
# participants affected / at risk     0/33 (0.00%)     1/26 (3.85%)     2/30 (6.67%)  
Oropharyngeal pain † 1      
# participants affected / at risk     4/33 (12.12%)     6/26 (23.08%)     1/30 (3.33%)  
Atelectasis † 1      
# participants affected / at risk     1/33 (3.03%)     0/26 (0.00%)     2/30 (6.67%)  
Dyspnoea † 1      
# participants affected / at risk     3/33 (9.09%)     6/26 (23.08%)     6/30 (20.00%)  
Productive cough † 1      
# participants affected / at risk     1/33 (3.03%)     1/26 (3.85%)     4/30 (13.33%)  
Rhonchi † 1      
# participants affected / at risk     0/33 (0.00%)     0/26 (0.00%)     2/30 (6.67%)  
Pulmonary oedema † 1      
# participants affected / at risk     2/33 (6.06%)     0/26 (0.00%)     0/30 (0.00%)  
Nasal congestion † 1      
# participants affected / at risk     3/33 (9.09%)     0/26 (0.00%)     1/30 (3.33%)  
Rales † 1      
# participants affected / at risk     2/33 (6.06%)     2/26 (7.69%)     3/30 (10.00%)  
Sinus congestion † 1      
# participants affected / at risk     2/33 (6.06%)     0/26 (0.00%)     0/30 (0.00%)  
Cough † 1      
# participants affected / at risk     7/33 (21.21%)     3/26 (11.54%)     5/30 (16.67%)  
Epistaxis † 1      
# participants affected / at risk     1/33 (3.03%)     4/26 (15.38%)     0/30 (0.00%)  
Skin and subcutaneous tissue disorders        
Pruritus † 1      
# participants affected / at risk     4/33 (12.12%)     3/26 (11.54%)     4/30 (13.33%)  
Blister † 1      
# participants affected / at risk     1/33 (3.03%)     2/26 (7.69%)     1/30 (3.33%)  
Actinic keratosis † 1      
# participants affected / at risk     1/33 (3.03%)     1/26 (3.85%)     4/30 (13.33%)  
Eczema † 1      
# participants affected / at risk     0/33 (0.00%)     0/26 (0.00%)     2/30 (6.67%)  
Night sweats † 1      
# participants affected / at risk     1/33 (3.03%)     0/26 (0.00%)     2/30 (6.67%)  
Erythema † 1      
# participants affected / at risk     0/33 (0.00%)     0/26 (0.00%)     3/30 (10.00%)  
Skin ulcer † 1      
# participants affected / at risk     1/33 (3.03%)     2/26 (7.69%)     1/30 (3.33%)  
Acne † 1      
# participants affected / at risk     0/33 (0.00%)     2/26 (7.69%)     1/30 (3.33%)  
Skin lesion † 1      
# participants affected / at risk     2/33 (6.06%)     2/26 (7.69%)     3/30 (10.00%)  
Alopecia † 1      
# participants affected / at risk     2/33 (6.06%)     1/26 (3.85%)     5/30 (16.67%)  
Rash † 1      
# participants affected / at risk     4/33 (12.12%)     5/26 (19.23%)     1/30 (3.33%)  
Vascular disorders        
Hot flush † 1      
# participants affected / at risk     2/33 (6.06%)     0/26 (0.00%)     0/30 (0.00%)  
Hypertension † 1      
# participants affected / at risk     11/33 (33.33%)     9/26 (34.62%)     13/30 (43.33%)  
Hypotension † 1      
# participants affected / at risk     7/33 (21.21%)     4/26 (15.38%)     4/30 (13.33%)  
Bloody discharge † 1      
# participants affected / at risk     1/33 (3.03%)     1/26 (3.85%)     2/30 (6.67%)  
Orthostatic hypotension † 1      
# participants affected / at risk     1/33 (3.03%)     2/26 (7.69%)     1/30 (3.33%)  
Events were collected by systematic assessment
1 Term from vocabulary, MedDRA 15.0



  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
Main limitations of this study include: small size (small number of participants in each treatment arm), the open-label nature of the trial, its exploratory nature, and the high rate of switches from sirolimus to MMF in one of the belatacept groups.


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