Trial Outcomes & Findings for Trial to Evaluate Safety and Tolerability of Tacrolimus Extended-Release (Astagraf XL) in Human Leukocyte Antigen (HLA) Sensitized Kidney Transplant Recipients (NCT NCT03194321)
NCT ID: NCT03194321
Last Updated: 2022-01-19
Results Overview
To determine the safety of tacrolimus extended-release in HS kidney transplant recipients after desensitization with intravenous immunoglobulin (IVIG) and rituximab +/- plasma exchange (PLEX) per the standard of care and alemtuzumab induction. This will be measured by the rate of serious adverse events (SAEs) and treatment failure. Treatment failure is defined as a composite of biopsy proven acute rejection (BPAR), graft failure, or death. BPAR is defined as ≥ Banff 1A using the Banff 2007 criteria.
COMPLETED
PHASE4
20 participants
12 months
2022-01-19
Participant Flow
Male and female HLA sensitized (HS) renal transplantation patients, 18 years of age and over, receiving a cadaveric or living donor kidney transplant may enter the study. Patients must receive desensitization therapy. Twenty patients will be enrolled at Cedars-Sinai Medical Center (CSMC) for this pilot study. Patients who discontinue the study prematurely will not be replaced.
Of the total 31 participants ages 18 years and older screened, 20 were enrolled in this single-center, open-label single-arm, non-controlled study.
Participant milestones
| Measure |
Tacrolimus Extended-Release Arm
All patients will receive tacrolimus extended-release adjusted to target trough levels, mycophenolate mofetil or mycophenolate sodium, and prednisone per CSMC practice.
Tacrolimus Extended-Release Oral Capsule: Maintenance immunosuppression will consist of tacrolimus extended-release, mycophenolate mofetil 500mg twice daily or mycophenolate sodium 360mg twice daily, and prednisone.
|
|---|---|
|
Overall Study
STARTED
|
20
|
|
Overall Study
COMPLETED
|
17
|
|
Overall Study
NOT COMPLETED
|
3
|
Reasons for withdrawal
| Measure |
Tacrolimus Extended-Release Arm
All patients will receive tacrolimus extended-release adjusted to target trough levels, mycophenolate mofetil or mycophenolate sodium, and prednisone per CSMC practice.
Tacrolimus Extended-Release Oral Capsule: Maintenance immunosuppression will consist of tacrolimus extended-release, mycophenolate mofetil 500mg twice daily or mycophenolate sodium 360mg twice daily, and prednisone.
|
|---|---|
|
Overall Study
Withdrawal by Subject
|
1
|
|
Overall Study
Lost to Follow-up
|
1
|
|
Overall Study
Travel for Follow-up
|
1
|
Baseline Characteristics
Trial to Evaluate Safety and Tolerability of Tacrolimus Extended-Release (Astagraf XL) in Human Leukocyte Antigen (HLA) Sensitized Kidney Transplant Recipients
Baseline characteristics by cohort
| Measure |
Tacrolimus Extended-Release Arm
n=20 Participants
All patients will receive tacrolimus extended-release adjusted to target trough levels, mycophenolate mofetil or mycophenolate sodium, and prednisone per CSMC practice.
Tacrolimus Extended-Release Oral Capsule: Maintenance immunosuppression will consist of tacrolimus extended-release, mycophenolate mofetil 500mg twice daily or mycophenolate sodium 360mg twice daily, and prednisone.
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=99 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
19 Participants
n=99 Participants
|
|
Age, Categorical
>=65 years
|
1 Participants
n=99 Participants
|
|
Age, Continuous
|
45 years
STANDARD_DEVIATION 10.4956 • n=99 Participants
|
|
Sex: Female, Male
Female
|
12 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
8 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
6 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
14 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Asian
|
4 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
1 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=99 Participants
|
|
Race (NIH/OMB)
White
|
13 Participants
n=99 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
PRIMARY outcome
Timeframe: 12 monthsPopulation: All participants who completed their 12 month visit were assessed.
To determine the safety of tacrolimus extended-release in HS kidney transplant recipients after desensitization with intravenous immunoglobulin (IVIG) and rituximab +/- plasma exchange (PLEX) per the standard of care and alemtuzumab induction. This will be measured by the rate of serious adverse events (SAEs) and treatment failure. Treatment failure is defined as a composite of biopsy proven acute rejection (BPAR), graft failure, or death. BPAR is defined as ≥ Banff 1A using the Banff 2007 criteria.
Outcome measures
| Measure |
Tacrolimus Extended-Release Arm
n=17 Participants
All patients will receive tacrolimus extended-release adjusted to target trough levels, mycophenolate mofetil or mycophenolate sodium, and prednisone per CSMC practice.
Tacrolimus Extended-Release Oral Capsule: Maintenance immunosuppression will consist of tacrolimus extended-release, mycophenolate mofetil 500mg twice daily or mycophenolate sodium 360mg twice daily, and prednisone.
|
|---|---|
|
Number of Participants With Treatment-related Adverse Events and Treatment Failure
Active/Chronic Antibody Mediated Rejection (cABMR)
|
2 Participants
|
|
Number of Participants With Treatment-related Adverse Events and Treatment Failure
Chronic active Cell Mediated Rejection (CMR)/Antibody Mediated Rejection (ABMR)
|
2 Participants
|
|
Number of Participants With Treatment-related Adverse Events and Treatment Failure
Early Transplant Glomerulopathy (TG)
|
1 Participants
|
|
Number of Participants With Treatment-related Adverse Events and Treatment Failure
Cell Mediated Rejection (CMR)
|
1 Participants
|
|
Number of Participants With Treatment-related Adverse Events and Treatment Failure
Infections (i.e. BK Viremia, Cytomegalovirus (CMV)))
|
4 Participants
|
SECONDARY outcome
Timeframe: Transplant, 1 month, 3 months, 6 months, 9 months, and 12 monthsPopulation: All participants enrolled were assessed. Number of participants analyzed differed due to study withdrawals prior to 12 months.
To observe the change in DSA as defined by the DSA RIS, which is defined by: 0 points for no DSA, 2 points for each weak DSA (MFI \<5,000), 5 points for each moderate DSA (MFI 5,000 -10,000), and 10 points for each strong DSA (MFI \>10,000).
Outcome measures
| Measure |
Tacrolimus Extended-Release Arm
n=20 Participants
All patients will receive tacrolimus extended-release adjusted to target trough levels, mycophenolate mofetil or mycophenolate sodium, and prednisone per CSMC practice.
Tacrolimus Extended-Release Oral Capsule: Maintenance immunosuppression will consist of tacrolimus extended-release, mycophenolate mofetil 500mg twice daily or mycophenolate sodium 360mg twice daily, and prednisone.
|
|---|---|
|
Change in Donor Specific Antibodies (DSA) as Defined by the DSA Relative Intensity Score (RIS)
DSA RIS @ Transplant
|
3.21 DSA Relative Intensity Score
Standard Deviation 2.86
|
|
Change in Donor Specific Antibodies (DSA) as Defined by the DSA Relative Intensity Score (RIS)
DSA RIS @ Month 1
|
0.79 DSA Relative Intensity Score
Standard Deviation 1.69
|
|
Change in Donor Specific Antibodies (DSA) as Defined by the DSA Relative Intensity Score (RIS)
DSA RIS @ Month 3
|
0.64 DSA Relative Intensity Score
Standard Deviation 1.97
|
|
Change in Donor Specific Antibodies (DSA) as Defined by the DSA Relative Intensity Score (RIS)
DSA RIS @ Month 6
|
0.93 DSA Relative Intensity Score
Standard Deviation 2.70
|
|
Change in Donor Specific Antibodies (DSA) as Defined by the DSA Relative Intensity Score (RIS)
DSA RIS @ Month 9
|
0.86 DSA Relative Intensity Score
Standard Deviation 2.26
|
|
Change in Donor Specific Antibodies (DSA) as Defined by the DSA Relative Intensity Score (RIS)
DSA RIS @ Month 12
|
1.14 DSA Relative Intensity Score
Standard Deviation 2.49
|
SECONDARY outcome
Timeframe: 12 monthsPopulation: All participants enrolled were assessed.
To observe the tolerability as defined by the number of subjects discontinuing the study medication.
Outcome measures
| Measure |
Tacrolimus Extended-Release Arm
n=20 Participants
All patients will receive tacrolimus extended-release adjusted to target trough levels, mycophenolate mofetil or mycophenolate sodium, and prednisone per CSMC practice.
Tacrolimus Extended-Release Oral Capsule: Maintenance immunosuppression will consist of tacrolimus extended-release, mycophenolate mofetil 500mg twice daily or mycophenolate sodium 360mg twice daily, and prednisone.
|
|---|---|
|
Tolerability as Defined by the Number of Subjects Discontinuing the Study Medication
|
3 Participants
|
Adverse Events
Tacrolimus Extended-Release Arm
Serious adverse events
| Measure |
Tacrolimus Extended-Release Arm
n=20 participants at risk
All patients will receive tacrolimus extended-release adjusted to target trough levels, mycophenolate mofetil or mycophenolate sodium, and prednisone per CSMC practice.
Tacrolimus Extended-Release Oral Capsule: Maintenance immunosuppression will consist of tacrolimus extended-release, mycophenolate mofetil 500mg twice daily or mycophenolate sodium 360mg twice daily, and prednisone.
|
|---|---|
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Blood and lymphatic system disorders
Bacteremia
|
5.0%
1/20 • 12 months
Adverse events and severe adverse events were collected and reported in all enrolled participants who received study drug.
|
|
General disorders
Diabetic ketoacidosis (DKA)
|
5.0%
1/20 • 12 months
Adverse events and severe adverse events were collected and reported in all enrolled participants who received study drug.
|
|
Renal and urinary disorders
Incisional abscess and acute kidney injury
|
5.0%
1/20 • 12 months
Adverse events and severe adverse events were collected and reported in all enrolled participants who received study drug.
|
Other adverse events
| Measure |
Tacrolimus Extended-Release Arm
n=20 participants at risk
All patients will receive tacrolimus extended-release adjusted to target trough levels, mycophenolate mofetil or mycophenolate sodium, and prednisone per CSMC practice.
Tacrolimus Extended-Release Oral Capsule: Maintenance immunosuppression will consist of tacrolimus extended-release, mycophenolate mofetil 500mg twice daily or mycophenolate sodium 360mg twice daily, and prednisone.
|
|---|---|
|
Immune system disorders
Mouth ulcer
|
5.0%
1/20 • 12 months
Adverse events and severe adverse events were collected and reported in all enrolled participants who received study drug.
|
|
Renal and urinary disorders
Perinephric fluid collection
|
5.0%
1/20 • 12 months
Adverse events and severe adverse events were collected and reported in all enrolled participants who received study drug.
|
|
Renal and urinary disorders
BKAN Grade 2 with stable Serum Creatinine
|
5.0%
1/20 • 12 months
Adverse events and severe adverse events were collected and reported in all enrolled participants who received study drug.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place