Trial Outcomes & Findings for A Study to Evaluate the Safety and Efficacy of Dual Costimulation Blockade With VIB4920 and Belatacept for Prophylaxis of Allograft Rejection in Adults Receiving a Kidney Transplant (NCT NCT04046549)
NCT ID: NCT04046549
Last Updated: 2024-12-27
Results Overview
Histological grading of acute allograft rejection from biopsy specimens was based on Banff criteria 2017. Grade IA: Moderate tubulitis and at least moderate total cortical inflammation and at least moderate scarred cortical inflammation and other known causes ruled out. Grade IB: Severe tubulitis and at least moderate total cortical inflammation and at least moderate scarred cortical inflammation and other known causes ruled out. Grade II. Arterial intimal fibrosis with mononuclear cell inflammation, formation of neointima.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
25 participants
Primary outcome timeframe
Week 24
Results posted on
2024-12-27
Participant Flow
A total of 25 participants underwent transplant surgery (enrolled); two of these participants were not treated, and are not included in any analysis. A total of 3 participants were enrolled prior to protocol version 3.
Participant milestones
| Measure |
Belatacept+VIB4920
Belatacept (protocol versions \[v\]1-4): 10 mg/kg by intravenous (IV) infusion on post-op Day 1, repeated on post-op Day 3 or 4, and at the end of Weeks 2, 4, 8, 12; then 5 mg/kg IV every 4 weeks from Week 16 to Week 48.
VIB4920 (protocol v1-2): 1500 mg by IV infusion on post-op Days 1 and 14, and at the end of Weeks 4, 6, 8, 10; then 1500 mg every 4 weeks from Week 12 to Week 48. Protocol v3-4: 1500 mg by IV infusion on post-op Days 1, repeated on post-op Day 3 or 4, Week 2, and at the end of Weeks 4, 6, 8, 10; then 1500 mg every 4 weeks from Week 12 to Week 48.
Thymoglobulin (protocol v1-2): 3.0 mg/kg by IV infusion prior to reperfusion of the allograft on the day of transplantation surgery (Day 0). Protocol v3-4: 1.5 mg/kg by IV infusion prior to reperfusion of the allograft on the day of transplantation surgery (Day 0), prior to VIB4920+belatacept infusion on post-op Day 1, on post-op Day 2, and prior to VIB4920+belatacept infusion on post-op Day 3 or 4.
Methylprednisolone (protocol v1-2): IV infusion (500, 250, 125, 60 mg on Days 0, 1, 2, 3, respectively); oral administration of prednisone 30 mg per day on Days 4, 5, 6. Protocol v3-4: IV infusion (500, 250, 125, 60 mg on Days 0, 1, 2, 3, respectively); oral administration of prednisone 30 mg per day on Days 4, 5, 6 and 7. Participants may be tapered to ≤ 20 mg per day on Day 8, to ≤ 10 mg per day on Day 15, and to ≤ 5 mg per day on Day 22. Discontinuation of prednisone following the post-op Day 28 visit.
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|---|---|
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Overall Study
STARTED
|
23
|
|
Overall Study
Enrolled Prior to Protocol V3.0
|
3
|
|
Overall Study
COMPLETED
|
13
|
|
Overall Study
NOT COMPLETED
|
10
|
Reasons for withdrawal
| Measure |
Belatacept+VIB4920
Belatacept (protocol versions \[v\]1-4): 10 mg/kg by intravenous (IV) infusion on post-op Day 1, repeated on post-op Day 3 or 4, and at the end of Weeks 2, 4, 8, 12; then 5 mg/kg IV every 4 weeks from Week 16 to Week 48.
VIB4920 (protocol v1-2): 1500 mg by IV infusion on post-op Days 1 and 14, and at the end of Weeks 4, 6, 8, 10; then 1500 mg every 4 weeks from Week 12 to Week 48. Protocol v3-4: 1500 mg by IV infusion on post-op Days 1, repeated on post-op Day 3 or 4, Week 2, and at the end of Weeks 4, 6, 8, 10; then 1500 mg every 4 weeks from Week 12 to Week 48.
Thymoglobulin (protocol v1-2): 3.0 mg/kg by IV infusion prior to reperfusion of the allograft on the day of transplantation surgery (Day 0). Protocol v3-4: 1.5 mg/kg by IV infusion prior to reperfusion of the allograft on the day of transplantation surgery (Day 0), prior to VIB4920+belatacept infusion on post-op Day 1, on post-op Day 2, and prior to VIB4920+belatacept infusion on post-op Day 3 or 4.
Methylprednisolone (protocol v1-2): IV infusion (500, 250, 125, 60 mg on Days 0, 1, 2, 3, respectively); oral administration of prednisone 30 mg per day on Days 4, 5, 6. Protocol v3-4: IV infusion (500, 250, 125, 60 mg on Days 0, 1, 2, 3, respectively); oral administration of prednisone 30 mg per day on Days 4, 5, 6 and 7. Participants may be tapered to ≤ 20 mg per day on Day 8, to ≤ 10 mg per day on Day 15, and to ≤ 5 mg per day on Day 22. Discontinuation of prednisone following the post-op Day 28 visit.
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|---|---|
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Overall Study
Adverse Event
|
1
|
|
Overall Study
Physician Decision
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1
|
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Overall Study
Withdrawal by Subject
|
3
|
|
Overall Study
Other, Not Specified
|
5
|
Baseline Characteristics
A Study to Evaluate the Safety and Efficacy of Dual Costimulation Blockade With VIB4920 and Belatacept for Prophylaxis of Allograft Rejection in Adults Receiving a Kidney Transplant
Baseline characteristics by cohort
| Measure |
Belatacept+VIB4920
n=23 Participants
Belatacept (protocol versions \[v\]1-4): 10 mg/kg by intravenous (IV) infusion on post-op Day 1, repeated on post-op Day 3 or 4, and at the end of Weeks 2, 4, 8, 12; then 5 mg/kg IV every 4 weeks from Week 16 to Week 48.
VIB4920 (protocol v1-2): 1500 mg by IV infusion on post-op Days 1 and 14, and at the end of Weeks 4, 6, 8, 10; then 1500 mg every 4 weeks from Week 12 to Week 48. Protocol v3-4: 1500 mg by IV infusion on post-op Days 1, repeated on post-op Day 3 or 4, Week 2, and at the end of Weeks 4, 6, 8, 10; then 1500 mg every 4 weeks from Week 12 to Week 48.
Thymoglobulin (protocol v1-2): 3.0 mg/kg by IV infusion prior to reperfusion of the allograft on the day of transplantation surgery (Day 0). Protocol v3-4: 1.5 mg/kg by IV infusion prior to reperfusion of the allograft on the day of transplantation surgery (Day 0), prior to VIB4920+belatacept infusion on post-op Day 1, on post-op Day 2, and prior to VIB4920+belatacept infusion on post-op Day 3 or 4.
Methylprednisolone (protocol v1-2): IV infusion (500, 250, 125, 60 mg on Days 0, 1, 2, 3, respectively); oral administration of prednisone 30 mg per day on Days 4, 5, 6. Protocol v3-4: IV infusion (500, 250, 125, 60 mg on Days 0, 1, 2, 3, respectively); oral administration of prednisone 30 mg per day on Days 4, 5, 6 and 7. Participants may be tapered to ≤ 20 mg per day on Day 8, to ≤ 10 mg per day on Day 15, and to ≤ 5 mg per day on Day 22. Discontinuation of prednisone following the post-op Day 28 visit.
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|---|---|
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Age, Continuous
|
47.7 years
STANDARD_DEVIATION 12.4 • n=5 Participants
|
|
Sex: Female, Male
Female
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4 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
19 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
8 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
15 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
16 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
5 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Week 24Population: Efficacy Evaluable Set: All participants who received the revised regimen of Thymoglobulin and steroids, and any dose of investigational product (IP). Participants enrolled in protocol v3 - 4 were included in the analysis.
Histological grading of acute allograft rejection from biopsy specimens was based on Banff criteria 2017. Grade IA: Moderate tubulitis and at least moderate total cortical inflammation and at least moderate scarred cortical inflammation and other known causes ruled out. Grade IB: Severe tubulitis and at least moderate total cortical inflammation and at least moderate scarred cortical inflammation and other known causes ruled out. Grade II. Arterial intimal fibrosis with mononuclear cell inflammation, formation of neointima.
Outcome measures
| Measure |
Belatacept+VIB4920
n=20 Participants
Belatacept (protocol versions \[v\]3-4): 10 mg/kg by intravenous (IV) infusion on post-op Day 1, repeated on post-op Day 3 or 4, and at the end of Weeks 2, 4, 8, 12; then 5 mg/kg IV every 4 weeks from Week 16 to Week 48.
VIB4920 (protocol v3-4): 1500 mg by IV infusion on post-op Days 1, repeated on post-op Day 3 or 4, Week 2, and at the end of Weeks 4, 6, 8, 10; then 1500 mg every 4 weeks from Week 12 to Week 48.
Thymoglobulin (protocol v3-4): 1.5 mg/kg by IV infusion prior to reperfusion of the allograft on the day of transplantation surgery (Day 0), prior to VIB4920+belatacept infusion on post-op Day 1, on post-op Day 2, and prior to VIB4920+belatacept infusion on post-op Day 3 or 4.
Methylprednisolone (protocol v3-4): IV infusion (500, 250, 125, 60 mg on Days 0, 1, 2, 3, respectively); oral administration of prednisone 30 mg per day on Days 4, 5, 6 and 7. Participants may be tapered to ≤ 20 mg per day on Day 8, to ≤ 10 mg per day on Day 15, and to ≤ 5 mg per day on Day 22. Discontinuation of prednisone following the post-op Day 28 visit.
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|---|---|
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Percentage of Participants With Treated Biopsy-proven Acute Rejection (tBPAR) of Grade 1A or Higher, Graft Loss or Death at Week 24
|
25.0 percentage of participants
Interval 12.7 to 41.5
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SECONDARY outcome
Timeframe: Weeks 12 and 48Population: Efficacy Evaluable Set: All participants who received the revised regimen of Thymoglobulin and steroids, and any dose of IP. Participants enrolled in protocol v3 - 4 were included in the analysis.
Histological grading of acute allograft rejection from biopsy specimens was based on Banff criteria 2017. Grade IA: Moderate tubulitis and at least moderate total cortical inflammation and at least moderate scarred cortical inflammation and other known causes ruled out. Grade IB: Severe tubulitis and at least moderate total cortical inflammation and at least moderate scarred cortical inflammation and other known causes ruled out. Grade II. Arterial intimal fibrosis with mononuclear cell inflammation, formation of neointima.
Outcome measures
| Measure |
Belatacept+VIB4920
n=20 Participants
Belatacept (protocol versions \[v\]3-4): 10 mg/kg by intravenous (IV) infusion on post-op Day 1, repeated on post-op Day 3 or 4, and at the end of Weeks 2, 4, 8, 12; then 5 mg/kg IV every 4 weeks from Week 16 to Week 48.
VIB4920 (protocol v3-4): 1500 mg by IV infusion on post-op Days 1, repeated on post-op Day 3 or 4, Week 2, and at the end of Weeks 4, 6, 8, 10; then 1500 mg every 4 weeks from Week 12 to Week 48.
Thymoglobulin (protocol v3-4): 1.5 mg/kg by IV infusion prior to reperfusion of the allograft on the day of transplantation surgery (Day 0), prior to VIB4920+belatacept infusion on post-op Day 1, on post-op Day 2, and prior to VIB4920+belatacept infusion on post-op Day 3 or 4.
Methylprednisolone (protocol v3-4): IV infusion (500, 250, 125, 60 mg on Days 0, 1, 2, 3, respectively); oral administration of prednisone 30 mg per day on Days 4, 5, 6 and 7. Participants may be tapered to ≤ 20 mg per day on Day 8, to ≤ 10 mg per day on Day 15, and to ≤ 5 mg per day on Day 22. Discontinuation of prednisone following the post-op Day 28 visit.
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|---|---|
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Percentage of Participants With Treated Biopsy-proven Acute Rejection (tBPAR) of Grade 1A or Higher, Graft Loss or Death at Weeks 12 and 48
Week 12
|
25.0 percentage of participants
Interval 12.7 to 41.5
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|
Percentage of Participants With Treated Biopsy-proven Acute Rejection (tBPAR) of Grade 1A or Higher, Graft Loss or Death at Weeks 12 and 48
Week 48
|
25.0 percentage of participants
Interval 12.7 to 41.5
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SECONDARY outcome
Timeframe: Week 12, 24, 48Population: Efficacy Evaluable Set: All participants who received the revised regimen of Thymoglobulin and steroids, and any dose of IP. Participants enrolled in protocol v3 - 4 were included in the analysis.
Histological grading of acute allograft rejection from biopsy specimens was based on Banff criteria 2017. Grade IA: Moderate tubulitis and at least moderate total cortical inflammation and at least moderate scarred cortical inflammation and other known causes ruled out. Grade IB: Severe tubulitis and at least moderate total cortical inflammation and at least moderate scarred cortical inflammation and other known causes ruled out. Grade II. Arterial intimal fibrosis with mononuclear cell inflammation, formation of neointima.
Outcome measures
| Measure |
Belatacept+VIB4920
n=20 Participants
Belatacept (protocol versions \[v\]3-4): 10 mg/kg by intravenous (IV) infusion on post-op Day 1, repeated on post-op Day 3 or 4, and at the end of Weeks 2, 4, 8, 12; then 5 mg/kg IV every 4 weeks from Week 16 to Week 48.
VIB4920 (protocol v3-4): 1500 mg by IV infusion on post-op Days 1, repeated on post-op Day 3 or 4, Week 2, and at the end of Weeks 4, 6, 8, 10; then 1500 mg every 4 weeks from Week 12 to Week 48.
Thymoglobulin (protocol v3-4): 1.5 mg/kg by IV infusion prior to reperfusion of the allograft on the day of transplantation surgery (Day 0), prior to VIB4920+belatacept infusion on post-op Day 1, on post-op Day 2, and prior to VIB4920+belatacept infusion on post-op Day 3 or 4.
Methylprednisolone (protocol v3-4): IV infusion (500, 250, 125, 60 mg on Days 0, 1, 2, 3, respectively); oral administration of prednisone 30 mg per day on Days 4, 5, 6 and 7. Participants may be tapered to ≤ 20 mg per day on Day 8, to ≤ 10 mg per day on Day 15, and to ≤ 5 mg per day on Day 22. Discontinuation of prednisone following the post-op Day 28 visit.
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|---|---|
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Percentage of Participants With Treated Biopsy-proven Acute Rejection (tBPAR), Graft Loss, Death or Loss to Follow-up (LTFU)
Week 12
|
25.0 percentage of participants
Interval 12.7 to 41.5
|
|
Percentage of Participants With Treated Biopsy-proven Acute Rejection (tBPAR), Graft Loss, Death or Loss to Follow-up (LTFU)
Week 24
|
25.0 percentage of participants
Interval 12.7 to 41.5
|
|
Percentage of Participants With Treated Biopsy-proven Acute Rejection (tBPAR), Graft Loss, Death or Loss to Follow-up (LTFU)
Week 48
|
25.0 percentage of participants
Interval 12.7 to 41.5
|
SECONDARY outcome
Timeframe: Week 12, 24, 48Population: Efficacy Evaluable Set: All participants who received the revised regimen of Thymoglobulin and steroids, and any dose of IP. Participants enrolled in protocol v3 - 4 were included in the analysis.
The diagnosis of antibody-mediated rejection was based on Banff criteria 2017 - a set of standardized guidelines used by pathologists and clinicians to diagnose and classify rejection based on specific features observed in biopsy samples from the transplanted organ, such as the presence of certain types of immune cells, inflammation, and injury patterns.
Outcome measures
| Measure |
Belatacept+VIB4920
n=20 Participants
Belatacept (protocol versions \[v\]3-4): 10 mg/kg by intravenous (IV) infusion on post-op Day 1, repeated on post-op Day 3 or 4, and at the end of Weeks 2, 4, 8, 12; then 5 mg/kg IV every 4 weeks from Week 16 to Week 48.
VIB4920 (protocol v3-4): 1500 mg by IV infusion on post-op Days 1, repeated on post-op Day 3 or 4, Week 2, and at the end of Weeks 4, 6, 8, 10; then 1500 mg every 4 weeks from Week 12 to Week 48.
Thymoglobulin (protocol v3-4): 1.5 mg/kg by IV infusion prior to reperfusion of the allograft on the day of transplantation surgery (Day 0), prior to VIB4920+belatacept infusion on post-op Day 1, on post-op Day 2, and prior to VIB4920+belatacept infusion on post-op Day 3 or 4.
Methylprednisolone (protocol v3-4): IV infusion (500, 250, 125, 60 mg on Days 0, 1, 2, 3, respectively); oral administration of prednisone 30 mg per day on Days 4, 5, 6 and 7. Participants may be tapered to ≤ 20 mg per day on Day 8, to ≤ 10 mg per day on Day 15, and to ≤ 5 mg per day on Day 22. Discontinuation of prednisone following the post-op Day 28 visit.
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|---|---|
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Percentage of Participants With Antibody-Mediated Rejection
Week 12
|
10.0 percentage of participants
Interval 2.7 to 24.5
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|
Percentage of Participants With Antibody-Mediated Rejection
Week 24
|
10.0 percentage of participants
Interval 2.7 to 24.5
|
|
Percentage of Participants With Antibody-Mediated Rejection
Week 48
|
15.0 percentage of participants
Interval 5.6 to 30.4
|
SECONDARY outcome
Timeframe: Week 12, 24, 48Population: Efficacy Evaluable Set: All participants who received the revised regimen of Thymoglobulin and steroids, and any dose of IP. Participants enrolled in protocol v3 - 4 were included in the analysis.
Histological grading of acute allograft rejection from biopsy specimens was based on Banff criteria 2017. Grade IA: Moderate tubulitis and at least moderate total cortical inflammation and at least moderate scarred cortical inflammation and other known causes ruled out. Grade IB: Severe tubulitis and at least moderate total cortical inflammation and at least moderate scarred cortical inflammation and other known causes ruled out. Grade II. Arterial intimal fibrosis with mononuclear cell inflammation, formation of neointima. tBPAR was defined as a BPAR which was treated with anti-rejection therapy.
Outcome measures
| Measure |
Belatacept+VIB4920
n=20 Participants
Belatacept (protocol versions \[v\]3-4): 10 mg/kg by intravenous (IV) infusion on post-op Day 1, repeated on post-op Day 3 or 4, and at the end of Weeks 2, 4, 8, 12; then 5 mg/kg IV every 4 weeks from Week 16 to Week 48.
VIB4920 (protocol v3-4): 1500 mg by IV infusion on post-op Days 1, repeated on post-op Day 3 or 4, Week 2, and at the end of Weeks 4, 6, 8, 10; then 1500 mg every 4 weeks from Week 12 to Week 48.
Thymoglobulin (protocol v3-4): 1.5 mg/kg by IV infusion prior to reperfusion of the allograft on the day of transplantation surgery (Day 0), prior to VIB4920+belatacept infusion on post-op Day 1, on post-op Day 2, and prior to VIB4920+belatacept infusion on post-op Day 3 or 4.
Methylprednisolone (protocol v3-4): IV infusion (500, 250, 125, 60 mg on Days 0, 1, 2, 3, respectively); oral administration of prednisone 30 mg per day on Days 4, 5, 6 and 7. Participants may be tapered to ≤ 20 mg per day on Day 8, to ≤ 10 mg per day on Day 15, and to ≤ 5 mg per day on Day 22. Discontinuation of prednisone following the post-op Day 28 visit.
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|---|---|
|
Percentage of Participants With Treated Biopsy-proven Acute Rejection (tBPAR)
Week 12
|
25.0 percentage of participants
Interval 12.7 to 41.5
|
|
Percentage of Participants With Treated Biopsy-proven Acute Rejection (tBPAR)
Week 24
|
25.0 percentage of participants
Interval 12.7 to 41.5
|
|
Percentage of Participants With Treated Biopsy-proven Acute Rejection (tBPAR)
Week 48
|
25.0 percentage of participants
Interval 12.7 to 41.5
|
SECONDARY outcome
Timeframe: Week 12, 24, 48Population: Efficacy Evaluable Set: All participants who received the revised regimen of Thymoglobulin and steroids, and any dose of IP. Participants enrolled in protocol v3 - 4 were included in the analysis.
Histological grading of acute allograft rejection from biopsy specimens was based on Banff criteria 2017. Grade IA: Moderate tubulitis and at least moderate total cortical inflammation and at least moderate scarred cortical inflammation and other known causes ruled out. Grade IB: Severe tubulitis and at least moderate total cortical inflammation and at least moderate scarred cortical inflammation and other known causes ruled out. Grade II. Arterial intimal fibrosis with mononuclear cell inflammation, formation of neointima.
Outcome measures
| Measure |
Belatacept+VIB4920
n=20 Participants
Belatacept (protocol versions \[v\]3-4): 10 mg/kg by intravenous (IV) infusion on post-op Day 1, repeated on post-op Day 3 or 4, and at the end of Weeks 2, 4, 8, 12; then 5 mg/kg IV every 4 weeks from Week 16 to Week 48.
VIB4920 (protocol v3-4): 1500 mg by IV infusion on post-op Days 1, repeated on post-op Day 3 or 4, Week 2, and at the end of Weeks 4, 6, 8, 10; then 1500 mg every 4 weeks from Week 12 to Week 48.
Thymoglobulin (protocol v3-4): 1.5 mg/kg by IV infusion prior to reperfusion of the allograft on the day of transplantation surgery (Day 0), prior to VIB4920+belatacept infusion on post-op Day 1, on post-op Day 2, and prior to VIB4920+belatacept infusion on post-op Day 3 or 4.
Methylprednisolone (protocol v3-4): IV infusion (500, 250, 125, 60 mg on Days 0, 1, 2, 3, respectively); oral administration of prednisone 30 mg per day on Days 4, 5, 6 and 7. Participants may be tapered to ≤ 20 mg per day on Day 8, to ≤ 10 mg per day on Day 15, and to ≤ 5 mg per day on Day 22. Discontinuation of prednisone following the post-op Day 28 visit.
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|---|---|
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Percentage of Participants With Biopsy Proven Acute Rejection (BPAR)
Week 12
|
25.0 percentage of participants
Interval 12.7 to 41.5
|
|
Percentage of Participants With Biopsy Proven Acute Rejection (BPAR)
Week 24
|
25.0 percentage of participants
Interval 12.7 to 41.5
|
|
Percentage of Participants With Biopsy Proven Acute Rejection (BPAR)
Week 48
|
25.0 percentage of participants
Interval 12.7 to 41.5
|
SECONDARY outcome
Timeframe: Week 12, 24, 48Population: Efficacy Evaluable Set: All participants who received the revised regimen of Thymoglobulin and steroids, and any dose of IP. Participants enrolled in protocol v3 - 4 were included in the analysis.
Acute rejections, per clinical judgement of the investigator followed by confirmatory biopsy, were treated with bolus methylprednisolone (other corticosteroids were acceptable at an equivalent dose) according to local practice.
Outcome measures
| Measure |
Belatacept+VIB4920
n=20 Participants
Belatacept (protocol versions \[v\]3-4): 10 mg/kg by intravenous (IV) infusion on post-op Day 1, repeated on post-op Day 3 or 4, and at the end of Weeks 2, 4, 8, 12; then 5 mg/kg IV every 4 weeks from Week 16 to Week 48.
VIB4920 (protocol v3-4): 1500 mg by IV infusion on post-op Days 1, repeated on post-op Day 3 or 4, Week 2, and at the end of Weeks 4, 6, 8, 10; then 1500 mg every 4 weeks from Week 12 to Week 48.
Thymoglobulin (protocol v3-4): 1.5 mg/kg by IV infusion prior to reperfusion of the allograft on the day of transplantation surgery (Day 0), prior to VIB4920+belatacept infusion on post-op Day 1, on post-op Day 2, and prior to VIB4920+belatacept infusion on post-op Day 3 or 4.
Methylprednisolone (protocol v3-4): IV infusion (500, 250, 125, 60 mg on Days 0, 1, 2, 3, respectively); oral administration of prednisone 30 mg per day on Days 4, 5, 6 and 7. Participants may be tapered to ≤ 20 mg per day on Day 8, to ≤ 10 mg per day on Day 15, and to ≤ 5 mg per day on Day 22. Discontinuation of prednisone following the post-op Day 28 visit.
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|---|---|
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Percentage of Participants With Treated Acute Rejections
Week 12
|
25.0 percentage of participants
Interval 12.7 to 41.5
|
|
Percentage of Participants With Treated Acute Rejections
Week 24
|
25.0 percentage of participants
Interval 12.7 to 41.5
|
|
Percentage of Participants With Treated Acute Rejections
Week 48
|
30.0 percentage of participants
Interval 16.7 to 46.7
|
SECONDARY outcome
Timeframe: Week 12, 24, 48Serum samples were collected for de novo donor-specific antibodies (dnDSA) using solid phase (bead-based) assays.
Outcome measures
Outcome data not reported
Adverse Events
Belatacept+VIB4920
Serious events: 10 serious events
Other events: 20 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Belatacept+VIB4920
n=23 participants at risk
Belatacept (protocol versions \[v\]1-4): 10 mg/kg by intravenous (IV) infusion on post-op Day 1, repeated on post-op Day 3 or 4, and at the end of Weeks 2, 4, 8, 12; then 5 mg/kg IV every 4 weeks from Week 16 to Week 48.
VIB4920 (protocol v1-2): 1500 mg by IV infusion on post-op Days 1 and 14, and at the end of Weeks 4, 6, 8, 10; then 1500 mg every 4 weeks from Week 12 to Week 48. Protocol v3-4: 1500 mg by IV infusion on post-op Days 1, repeated on post-op Day 3 or 4, Week 2, and at the end of Weeks 4, 6, 8, 10; then 1500 mg every 4 weeks from Week 12 to Week 48.
Thymoglobulin (protocol v1-2): 3.0 mg/kg by IV infusion prior to reperfusion of the allograft on the day of transplantation surgery (Day 0). Protocol v3-4: 1.5 mg/kg by IV infusion prior to reperfusion of the allograft on the day of transplantation surgery (Day 0), prior to VIB4920+belatacept infusion on post-op Day 1, on post-op Day 2, and prior to VIB4920+belatacept infusion on post-op Day 3 or 4.
Methylprednisolone (protocol v1-2): IV infusion (500, 250, 125, 60 mg on Days 0, 1, 2, 3, respectively); oral administration of prednisone 30 mg per day on Days 4, 5, 6. Protocol v3-4: IV infusion (500, 250, 125, 60 mg on Days 0, 1, 2, 3, respectively); oral administration of prednisone 30 mg per day on Days 4, 5, 6 and 7. Participants may be tapered to ≤ 20 mg per day on Day 8, to ≤ 10 mg per day on Day 15, and to ≤ 5 mg per day on Day 22. Discontinuation of prednisone following the post-op Day 28 visit.
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|---|---|
|
Gastrointestinal disorders
Ileus
|
4.3%
1/23 • All-Cause Mortality: From written informed consent signature (Day -28 to -1) and the end of the safety follow-up 60 weeks (up to 64 weeks) Adverse Events: From first dose of study drug until the end of treatment + 12 weeks (up to 60 weeks)
As it is in our pre-specified analysis, all safety data was based on safety analysis set, i.e., all subjects who received any dose of IP.
|
|
Hepatobiliary disorders
Cholecystitis acute
|
4.3%
1/23 • All-Cause Mortality: From written informed consent signature (Day -28 to -1) and the end of the safety follow-up 60 weeks (up to 64 weeks) Adverse Events: From first dose of study drug until the end of treatment + 12 weeks (up to 60 weeks)
As it is in our pre-specified analysis, all safety data was based on safety analysis set, i.e., all subjects who received any dose of IP.
|
|
Immune system disorders
Kidney transplant rejection
|
4.3%
1/23 • All-Cause Mortality: From written informed consent signature (Day -28 to -1) and the end of the safety follow-up 60 weeks (up to 64 weeks) Adverse Events: From first dose of study drug until the end of treatment + 12 weeks (up to 60 weeks)
As it is in our pre-specified analysis, all safety data was based on safety analysis set, i.e., all subjects who received any dose of IP.
|
|
Infections and infestations
Bacteraemia
|
4.3%
1/23 • All-Cause Mortality: From written informed consent signature (Day -28 to -1) and the end of the safety follow-up 60 weeks (up to 64 weeks) Adverse Events: From first dose of study drug until the end of treatment + 12 weeks (up to 60 weeks)
As it is in our pre-specified analysis, all safety data was based on safety analysis set, i.e., all subjects who received any dose of IP.
|
|
Infections and infestations
Clostridium difficile infection
|
4.3%
1/23 • All-Cause Mortality: From written informed consent signature (Day -28 to -1) and the end of the safety follow-up 60 weeks (up to 64 weeks) Adverse Events: From first dose of study drug until the end of treatment + 12 weeks (up to 60 weeks)
As it is in our pre-specified analysis, all safety data was based on safety analysis set, i.e., all subjects who received any dose of IP.
|
|
Infections and infestations
Diabetic foot infection
|
4.3%
1/23 • All-Cause Mortality: From written informed consent signature (Day -28 to -1) and the end of the safety follow-up 60 weeks (up to 64 weeks) Adverse Events: From first dose of study drug until the end of treatment + 12 weeks (up to 60 weeks)
As it is in our pre-specified analysis, all safety data was based on safety analysis set, i.e., all subjects who received any dose of IP.
|
|
Infections and infestations
Urinary tract infection
|
4.3%
1/23 • All-Cause Mortality: From written informed consent signature (Day -28 to -1) and the end of the safety follow-up 60 weeks (up to 64 weeks) Adverse Events: From first dose of study drug until the end of treatment + 12 weeks (up to 60 weeks)
As it is in our pre-specified analysis, all safety data was based on safety analysis set, i.e., all subjects who received any dose of IP.
|
|
Infections and infestations
Urosepsis
|
4.3%
1/23 • All-Cause Mortality: From written informed consent signature (Day -28 to -1) and the end of the safety follow-up 60 weeks (up to 64 weeks) Adverse Events: From first dose of study drug until the end of treatment + 12 weeks (up to 60 weeks)
As it is in our pre-specified analysis, all safety data was based on safety analysis set, i.e., all subjects who received any dose of IP.
|
|
Injury, poisoning and procedural complications
Arteriovenous fistula site complication
|
4.3%
1/23 • All-Cause Mortality: From written informed consent signature (Day -28 to -1) and the end of the safety follow-up 60 weeks (up to 64 weeks) Adverse Events: From first dose of study drug until the end of treatment + 12 weeks (up to 60 weeks)
As it is in our pre-specified analysis, all safety data was based on safety analysis set, i.e., all subjects who received any dose of IP.
|
|
Injury, poisoning and procedural complications
Post procedural urine leak
|
8.7%
2/23 • All-Cause Mortality: From written informed consent signature (Day -28 to -1) and the end of the safety follow-up 60 weeks (up to 64 weeks) Adverse Events: From first dose of study drug until the end of treatment + 12 weeks (up to 60 weeks)
As it is in our pre-specified analysis, all safety data was based on safety analysis set, i.e., all subjects who received any dose of IP.
|
|
Investigations
Blood creatinine increased
|
4.3%
1/23 • All-Cause Mortality: From written informed consent signature (Day -28 to -1) and the end of the safety follow-up 60 weeks (up to 64 weeks) Adverse Events: From first dose of study drug until the end of treatment + 12 weeks (up to 60 weeks)
As it is in our pre-specified analysis, all safety data was based on safety analysis set, i.e., all subjects who received any dose of IP.
|
|
Investigations
Cytomegalovirus test positive
|
4.3%
1/23 • All-Cause Mortality: From written informed consent signature (Day -28 to -1) and the end of the safety follow-up 60 weeks (up to 64 weeks) Adverse Events: From first dose of study drug until the end of treatment + 12 weeks (up to 60 weeks)
As it is in our pre-specified analysis, all safety data was based on safety analysis set, i.e., all subjects who received any dose of IP.
|
|
Metabolism and nutrition disorders
Hypervolaemia
|
4.3%
1/23 • All-Cause Mortality: From written informed consent signature (Day -28 to -1) and the end of the safety follow-up 60 weeks (up to 64 weeks) Adverse Events: From first dose of study drug until the end of treatment + 12 weeks (up to 60 weeks)
As it is in our pre-specified analysis, all safety data was based on safety analysis set, i.e., all subjects who received any dose of IP.
|
|
Psychiatric disorders
Depression suicidal
|
4.3%
1/23 • All-Cause Mortality: From written informed consent signature (Day -28 to -1) and the end of the safety follow-up 60 weeks (up to 64 weeks) Adverse Events: From first dose of study drug until the end of treatment + 12 weeks (up to 60 weeks)
As it is in our pre-specified analysis, all safety data was based on safety analysis set, i.e., all subjects who received any dose of IP.
|
|
Renal and urinary disorders
Subcapsular renal haematoma
|
4.3%
1/23 • All-Cause Mortality: From written informed consent signature (Day -28 to -1) and the end of the safety follow-up 60 weeks (up to 64 weeks) Adverse Events: From first dose of study drug until the end of treatment + 12 weeks (up to 60 weeks)
As it is in our pre-specified analysis, all safety data was based on safety analysis set, i.e., all subjects who received any dose of IP.
|
|
Renal and urinary disorders
Ureteric stenosis
|
4.3%
1/23 • All-Cause Mortality: From written informed consent signature (Day -28 to -1) and the end of the safety follow-up 60 weeks (up to 64 weeks) Adverse Events: From first dose of study drug until the end of treatment + 12 weeks (up to 60 weeks)
As it is in our pre-specified analysis, all safety data was based on safety analysis set, i.e., all subjects who received any dose of IP.
|
Other adverse events
| Measure |
Belatacept+VIB4920
n=23 participants at risk
Belatacept (protocol versions \[v\]1-4): 10 mg/kg by intravenous (IV) infusion on post-op Day 1, repeated on post-op Day 3 or 4, and at the end of Weeks 2, 4, 8, 12; then 5 mg/kg IV every 4 weeks from Week 16 to Week 48.
VIB4920 (protocol v1-2): 1500 mg by IV infusion on post-op Days 1 and 14, and at the end of Weeks 4, 6, 8, 10; then 1500 mg every 4 weeks from Week 12 to Week 48. Protocol v3-4: 1500 mg by IV infusion on post-op Days 1, repeated on post-op Day 3 or 4, Week 2, and at the end of Weeks 4, 6, 8, 10; then 1500 mg every 4 weeks from Week 12 to Week 48.
Thymoglobulin (protocol v1-2): 3.0 mg/kg by IV infusion prior to reperfusion of the allograft on the day of transplantation surgery (Day 0). Protocol v3-4: 1.5 mg/kg by IV infusion prior to reperfusion of the allograft on the day of transplantation surgery (Day 0), prior to VIB4920+belatacept infusion on post-op Day 1, on post-op Day 2, and prior to VIB4920+belatacept infusion on post-op Day 3 or 4.
Methylprednisolone (protocol v1-2): IV infusion (500, 250, 125, 60 mg on Days 0, 1, 2, 3, respectively); oral administration of prednisone 30 mg per day on Days 4, 5, 6. Protocol v3-4: IV infusion (500, 250, 125, 60 mg on Days 0, 1, 2, 3, respectively); oral administration of prednisone 30 mg per day on Days 4, 5, 6 and 7. Participants may be tapered to ≤ 20 mg per day on Day 8, to ≤ 10 mg per day on Day 15, and to ≤ 5 mg per day on Day 22. Discontinuation of prednisone following the post-op Day 28 visit.
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
17.4%
4/23 • All-Cause Mortality: From written informed consent signature (Day -28 to -1) and the end of the safety follow-up 60 weeks (up to 64 weeks) Adverse Events: From first dose of study drug until the end of treatment + 12 weeks (up to 60 weeks)
As it is in our pre-specified analysis, all safety data was based on safety analysis set, i.e., all subjects who received any dose of IP.
|
|
Blood and lymphatic system disorders
Leukopenia
|
17.4%
4/23 • All-Cause Mortality: From written informed consent signature (Day -28 to -1) and the end of the safety follow-up 60 weeks (up to 64 weeks) Adverse Events: From first dose of study drug until the end of treatment + 12 weeks (up to 60 weeks)
As it is in our pre-specified analysis, all safety data was based on safety analysis set, i.e., all subjects who received any dose of IP.
|
|
Blood and lymphatic system disorders
Neutropenia
|
8.7%
2/23 • All-Cause Mortality: From written informed consent signature (Day -28 to -1) and the end of the safety follow-up 60 weeks (up to 64 weeks) Adverse Events: From first dose of study drug until the end of treatment + 12 weeks (up to 60 weeks)
As it is in our pre-specified analysis, all safety data was based on safety analysis set, i.e., all subjects who received any dose of IP.
|
|
Infections and infestations
BK virus infection
|
17.4%
4/23 • All-Cause Mortality: From written informed consent signature (Day -28 to -1) and the end of the safety follow-up 60 weeks (up to 64 weeks) Adverse Events: From first dose of study drug until the end of treatment + 12 weeks (up to 60 weeks)
As it is in our pre-specified analysis, all safety data was based on safety analysis set, i.e., all subjects who received any dose of IP.
|
|
Infections and infestations
COVID-19
|
21.7%
5/23 • All-Cause Mortality: From written informed consent signature (Day -28 to -1) and the end of the safety follow-up 60 weeks (up to 64 weeks) Adverse Events: From first dose of study drug until the end of treatment + 12 weeks (up to 60 weeks)
As it is in our pre-specified analysis, all safety data was based on safety analysis set, i.e., all subjects who received any dose of IP.
|
|
Infections and infestations
Urinary tract infection
|
8.7%
2/23 • All-Cause Mortality: From written informed consent signature (Day -28 to -1) and the end of the safety follow-up 60 weeks (up to 64 weeks) Adverse Events: From first dose of study drug until the end of treatment + 12 weeks (up to 60 weeks)
As it is in our pre-specified analysis, all safety data was based on safety analysis set, i.e., all subjects who received any dose of IP.
|
|
Injury, poisoning and procedural complications
Procedural pain
|
8.7%
2/23 • All-Cause Mortality: From written informed consent signature (Day -28 to -1) and the end of the safety follow-up 60 weeks (up to 64 weeks) Adverse Events: From first dose of study drug until the end of treatment + 12 weeks (up to 60 weeks)
As it is in our pre-specified analysis, all safety data was based on safety analysis set, i.e., all subjects who received any dose of IP.
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
8.7%
2/23 • All-Cause Mortality: From written informed consent signature (Day -28 to -1) and the end of the safety follow-up 60 weeks (up to 64 weeks) Adverse Events: From first dose of study drug until the end of treatment + 12 weeks (up to 60 weeks)
As it is in our pre-specified analysis, all safety data was based on safety analysis set, i.e., all subjects who received any dose of IP.
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
17.4%
4/23 • All-Cause Mortality: From written informed consent signature (Day -28 to -1) and the end of the safety follow-up 60 weeks (up to 64 weeks) Adverse Events: From first dose of study drug until the end of treatment + 12 weeks (up to 60 weeks)
As it is in our pre-specified analysis, all safety data was based on safety analysis set, i.e., all subjects who received any dose of IP.
|
|
Metabolism and nutrition disorders
Metabolic acidosis
|
8.7%
2/23 • All-Cause Mortality: From written informed consent signature (Day -28 to -1) and the end of the safety follow-up 60 weeks (up to 64 weeks) Adverse Events: From first dose of study drug until the end of treatment + 12 weeks (up to 60 weeks)
As it is in our pre-specified analysis, all safety data was based on safety analysis set, i.e., all subjects who received any dose of IP.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
13.0%
3/23 • All-Cause Mortality: From written informed consent signature (Day -28 to -1) and the end of the safety follow-up 60 weeks (up to 64 weeks) Adverse Events: From first dose of study drug until the end of treatment + 12 weeks (up to 60 weeks)
As it is in our pre-specified analysis, all safety data was based on safety analysis set, i.e., all subjects who received any dose of IP.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
8.7%
2/23 • All-Cause Mortality: From written informed consent signature (Day -28 to -1) and the end of the safety follow-up 60 weeks (up to 64 weeks) Adverse Events: From first dose of study drug until the end of treatment + 12 weeks (up to 60 weeks)
As it is in our pre-specified analysis, all safety data was based on safety analysis set, i.e., all subjects who received any dose of IP.
|
|
Nervous system disorders
Headache
|
13.0%
3/23 • All-Cause Mortality: From written informed consent signature (Day -28 to -1) and the end of the safety follow-up 60 weeks (up to 64 weeks) Adverse Events: From first dose of study drug until the end of treatment + 12 weeks (up to 60 weeks)
As it is in our pre-specified analysis, all safety data was based on safety analysis set, i.e., all subjects who received any dose of IP.
|
|
Psychiatric disorders
Insomnia
|
8.7%
2/23 • All-Cause Mortality: From written informed consent signature (Day -28 to -1) and the end of the safety follow-up 60 weeks (up to 64 weeks) Adverse Events: From first dose of study drug until the end of treatment + 12 weeks (up to 60 weeks)
As it is in our pre-specified analysis, all safety data was based on safety analysis set, i.e., all subjects who received any dose of IP.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Horizon requests that any investigator/institution that plans on presenting/publishing results provide written notification of their request 60 days prior to their presentation/publication. Horizon requests that no presentation/publication will be instituted until 12 months after a study is completed, or after the first presentation/publication whichever occurs first. A delay may be proposed of a presentation/publication if Horizon needs to secure patent or proprietary protection.
- Publication restrictions are in place
Restriction type: OTHER