Trial Outcomes & Findings for Safety & Tolerability of Berinert® (C1 Inhibitor) Therapy to Prevent Rejection (NCT NCT01134510)
NCT ID: NCT01134510
Last Updated: 2017-03-21
Results Overview
Subjects will have a routine kidney biopsy 6 month after transplant to screen for episodes of acute rejection. For purposes of this investigation, antibody-mediated rejection (AMR) is defined as follows: * Deterioration of allograft function in a high-risk transplant recipient (i.e. sensitized patient with history of Donor Specific Antibodies) measured by serum Creatinine and estimated Glomerular Filtration Rate * Association with the presence of Donor Specific Antibody (usually increasing in strength) measured by luminex techniques. * Biopsy evidence of capillaritis, inflammation and C4d deposition.
COMPLETED
PHASE1/PHASE2
20 participants
6 month
2017-03-21
Participant Flow
Participant milestones
| Measure |
C1 Esterase Inhibitor
Patients receiving transplants will have pre-transplant labs for C1 INH levels, Complement 3 and Complement 4 obtained. In addition to the standard post-transplant immunosuppressive protocol, participating patients will receive 20 Units/kg C1 INH vs placebo (0.9% Normal Saline) on day 0 and day 2, then twice weekly X 3 weeks. A protocol biopsy will be performed at 6 month to assess the allograft for evidence of Antibody Mediated Rejection, including C4d staining using Banff 2009 criteria. After completion of the C1 INH therapy, patients will be followed up to 6M to assess allograft function and Anibody Mediated Rejection episodes as well as Donor Specific Antibody. A protocol biopsy will be performed at 6 month.
|
Placebo
Patients will receive placebo (0.9% Normal Saline) on days 0 and day 2, then twice weekly for 3 weeks.
|
|---|---|---|
|
Overall Study
STARTED
|
10
|
10
|
|
Overall Study
Day 2
|
10
|
10
|
|
Overall Study
Week 2
|
10
|
10
|
|
Overall Study
Week 3
|
10
|
10
|
|
Overall Study
Week 4
|
10
|
10
|
|
Overall Study
Month 1
|
10
|
10
|
|
Overall Study
Month 3
|
10
|
9
|
|
Overall Study
COMPLETED
|
10
|
9
|
|
Overall Study
NOT COMPLETED
|
0
|
1
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Safety & Tolerability of Berinert® (C1 Inhibitor) Therapy to Prevent Rejection
Baseline characteristics by cohort
| Measure |
C1 Esterase Inhibitor
n=10 Participants
Potential subjects will be identified after a review of medical records of patients under the care of one or more of the study investigators. Potential subjects will be identified and approached during an inpatient or outpatient clinical visit by a member of the research team. The Principal investigator (PI) I will explain what it means to be highly-sensitized and the risks associated with it. The PI will describe the study and explain the risks and benefits of participation. After the discussion, a copy of the consent form will be emailed or faxed to the patient for review \& consideration of study participation. The patient can contact the study team to ask questions and sign the Informed Consent Form (ICF), if interested.
C1 INH is dosed at 20 units per kg body weight and is administered by slow IV injection at a rate of approximately 4 mL per minute. Study patients will receive 20U/kg C1 INH vs placebo (0.9% NS) on days 0 and day 2, then twice weekly X 3 weeks.
|
Placebo
n=10 Participants
Potential subjects will be identified after a review of medical records of patients under the care of one or more of the study investigators. Potential subjects will be identified and approached during an inpatient or outpatient clinical visit by a member of the research team. The Principal investigator (PI) I will explain what it means to be highly-sensitized and the risks associated with it. Then PI will describe the standard of care of Transplant Immunology Program (TIP) patients. After that PI will describe the study and explain the risks and benefits of participation. After the discussion, a copy of the consent form will be either emailed or faxed to the patient for review and consideration of study participation. The patient can contact the study team where they will have the opportunity to ask questions and then sign the Informed Consent Form (ICF), if interested.
|
Total
n=20 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
10 Participants
n=93 Participants
|
10 Participants
n=4 Participants
|
20 Participants
n=27 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Age, Continuous
|
46 years
STANDARD_DEVIATION 14 • n=93 Participants
|
47 years
STANDARD_DEVIATION 16 • n=4 Participants
|
47 years
STANDARD_DEVIATION 15.5 • n=27 Participants
|
|
Sex: Female, Male
Female
|
8 Participants
n=93 Participants
|
3 Participants
n=4 Participants
|
11 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=93 Participants
|
7 Participants
n=4 Participants
|
9 Participants
n=27 Participants
|
|
Region of Enrollment
United States
|
10 participants
n=93 Participants
|
10 participants
n=4 Participants
|
20 participants
n=27 Participants
|
PRIMARY outcome
Timeframe: 6 monthPopulation: 9 patients in each arm completed 6 month protocol biopsy. 1 patient in the placebo arm was withdrawn before 6M biopsy. 1 patient in treatment arm refused protocol biopsy.
Subjects will have a routine kidney biopsy 6 month after transplant to screen for episodes of acute rejection. For purposes of this investigation, antibody-mediated rejection (AMR) is defined as follows: * Deterioration of allograft function in a high-risk transplant recipient (i.e. sensitized patient with history of Donor Specific Antibodies) measured by serum Creatinine and estimated Glomerular Filtration Rate * Association with the presence of Donor Specific Antibody (usually increasing in strength) measured by luminex techniques. * Biopsy evidence of capillaritis, inflammation and C4d deposition.
Outcome measures
| Measure |
C1 Esterase Inhibitor
n=9 Participants
10 subjects will receive C1 esterase inhibitor in addition to standard of care immunosuppressive therapy.
C1 Esterase Inhibitor: C1 Esterase Inhibitor 20 units/kg vs Placebo twice weekly x 4 weeks
|
Normal Saline
n=9 Participants
10 subjects placebo in addition to standard of care immunosuppressive therapy.
C1 Esterase Inhibitor: C1 Esterase Inhibitor 20 units/kg vs Placebo twice weekly x 4 weeks
|
|---|---|---|
|
Post-transplant Biopsy to Identify Rejection Episodes
|
2 Episode of rejection
|
3 Episode of rejection
|
SECONDARY outcome
Timeframe: 6 monthsPopulation: Mean serum creatinine levels at 6 month post-transplant from 10 patients in the C1 Esterase Inhibitor group and 10 patients in the placebo group were calculated.
Serum creatinine will be checked 6 months post transplant to monitor allograft function.
Outcome measures
| Measure |
C1 Esterase Inhibitor
n=10 Participants
10 subjects will receive C1 esterase inhibitor in addition to standard of care immunosuppressive therapy.
C1 Esterase Inhibitor: C1 Esterase Inhibitor 20 units/kg vs Placebo twice weekly x 4 weeks
|
Normal Saline
n=10 Participants
10 subjects placebo in addition to standard of care immunosuppressive therapy.
C1 Esterase Inhibitor: C1 Esterase Inhibitor 20 units/kg vs Placebo twice weekly x 4 weeks
|
|---|---|---|
|
Serum Creatinine
|
1.07 mg/dl (serum cr at 6m post transplant)
Standard Deviation 0.39
|
1.08 mg/dl (serum cr at 6m post transplant)
Standard Deviation 0.28
|
SECONDARY outcome
Timeframe: 6 monthsPopulation: Mean Donor Specific Antibody Class I levels at 1, 3, and 6 month post-transplant from 10 patients in the C1 Esterase Inhibitor group and 10 patients in the placebo group were calculated.
Donor Specific Antibodies \[DSAs\] Class I will be checked 1, 3, and 6 months post transplant to monitor allograft function. DSA will be measured using a relative intensity score (RIS) ranges from 0 points = No DSA; 2 points = \<5000MFI (weak intensity); 5 points = 5000-10,000 MFI (moderate intensty); 10 points = \>10,000MFI (strong intensity). Each DSA can have a score of 10 maximum. However, patients may have more than one DSA and points can add up to more than 10. this depends on how many DSAs \[Class I and/or Class II\] are present at the time of transplant and quarterly after transplant. Patients can have an infinite number of donor specific antibodies, this score can be higher than 10.
Outcome measures
| Measure |
C1 Esterase Inhibitor
n=10 Participants
10 subjects will receive C1 esterase inhibitor in addition to standard of care immunosuppressive therapy.
C1 Esterase Inhibitor: C1 Esterase Inhibitor 20 units/kg vs Placebo twice weekly x 4 weeks
|
Normal Saline
n=10 Participants
10 subjects placebo in addition to standard of care immunosuppressive therapy.
C1 Esterase Inhibitor: C1 Esterase Inhibitor 20 units/kg vs Placebo twice weekly x 4 weeks
|
|---|---|---|
|
Donor Specific Antibodies [DSA] Class I
|
10 DSA relative intensity score
Standard Deviation 9.3
|
7.1 DSA relative intensity score
Standard Deviation 4.8
|
SECONDARY outcome
Timeframe: 6 monthsPopulation: Mean Donor Specific Antibody (DSA) Class II levels at 1, 3, and 6 month post-transplant from 10 patients in the C1 Esterase Inhibitor group and 10 patients in the placebo group were calculated.
Donor Specific Antibodies \[DSAs\] Class I will be checked 1, 3, and 6 months post transplant to monitor allograft function. DSA will be measured using a relative intensity score (RIS) ranges from 0 points = No DSA; 2 points = \<5000MFI (weak intensity); 5 points = 5000-10,000 MFI (moderate intensty); 10 points = \>10,000MFI (strong intensity). Each DSA can have a score of 10 maximum. However, patients may have more than one DSA and points can add up to more than 10. this depends on how many DSAs \[Class I and/or Class II\] are present at the time of transplant and quarterly after transplant. However, patients may have more than one DSA and points can add up to more than 10 this depends on how many DSAs \[Class I and/or Class II\] are present at the time of transplant and quarterly after transplant. Patients can have an infinite number of donor specific antibodies, this score can be higher than 10.
Outcome measures
| Measure |
C1 Esterase Inhibitor
n=10 Participants
10 subjects will receive C1 esterase inhibitor in addition to standard of care immunosuppressive therapy.
C1 Esterase Inhibitor: C1 Esterase Inhibitor 20 units/kg vs Placebo twice weekly x 4 weeks
|
Normal Saline
n=10 Participants
10 subjects placebo in addition to standard of care immunosuppressive therapy.
C1 Esterase Inhibitor: C1 Esterase Inhibitor 20 units/kg vs Placebo twice weekly x 4 weeks
|
|---|---|---|
|
Donor Specific Antibodies [DSA] Class II
|
5.4 DSA relative intensity score
Standard Deviation 3.2
|
9.0 DSA relative intensity score
Standard Deviation 8.0
|
Adverse Events
Placebo
C1 Esterase Inhibitor
Serious adverse events
| Measure |
Placebo
n=10 participants at risk
Total of 2 Serious Adverse Events (2/10 patients = 20%)
|
C1 Esterase Inhibitor
n=10 participants at risk
Total of 1 Serious Adverse Event (1/10 = 10%)
|
|---|---|---|
|
Surgical and medical procedures
Post op Vascularization
|
50.0%
1/2 • Number of events 1 • 6 months
|
0.00%
0/10 • 6 months
|
|
Renal and urinary disorders
Hyperkalemia
|
10.0%
1/10 • Number of events 1 • 6 months
|
0.00%
0/10 • 6 months
|
|
Surgical and medical procedures
Perinephric Hematoma
|
0.00%
0/10 • 6 months
|
10.0%
1/10 • Number of events 1 • 6 months
|
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place