Trial Outcomes & Findings for Dosing Regimen of Eculizumab Added to Conventional Treatment in Positive Cross Match Living Donor Kidney Transplant (NCT NCT00670774)
NCT ID: NCT00670774
Last Updated: 2018-06-26
Results Overview
AMR can cause acute graft loss or shorten allograft survival. Renal allograft biopsies were obtained percutaneously using ultrasound guidance processed for light microscopy and immunofluorescence for peritubular capillary staining for C4d. All biopsies were reviewed by a pathologist in a blinded fashion. AMR was diagnosed using standard Banff criteria in combination with graft dysfunction (increase in serum creatinine \>/=0.3 mg/dL over nadir.)
COMPLETED
PHASE1/PHASE2
31 participants
up to 3 months
2018-06-26
Participant Flow
Consecutive kidney transplant patients recruited between 1/6/2008 and 1/8/2010 were recruited at Mayo Clinic in Rochester, Minnesota.
31 subjects signed informed consent, but 5 patients were screen failures and did not start the study.
Participant milestones
| Measure |
Eculizumab
Patients received eculizumab intravenously according to details provided in the intervention description.
|
|---|---|
|
Overall Study
STARTED
|
26
|
|
Overall Study
COMPLETED
|
26
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Dosing Regimen of Eculizumab Added to Conventional Treatment in Positive Cross Match Living Donor Kidney Transplant
Baseline characteristics by cohort
| Measure |
Eculizumab
n=26 Participants
Patients received eculizumab intravenously according to details provided in the intervention description.
|
|---|---|
|
Age, Continuous
|
48.6 years
STANDARD_DEVIATION 12.5 • n=99 Participants
|
|
Sex: Female, Male
Female
|
21 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=99 Participants
|
|
Race/Ethnicity, Customized
Caucasian white
|
24 Participants
n=99 Participants
|
|
Race/Ethnicity, Customized
Hispanic
|
2 Participants
n=99 Participants
|
|
Region of Enrollment
United States
|
26 Participants
n=99 Participants
|
|
Donor Specific Alloantibody
|
330 MCF shift from NC
STANDARD_DEVIATION 84 • n=99 Participants
|
PRIMARY outcome
Timeframe: up to 3 monthsAMR can cause acute graft loss or shorten allograft survival. Renal allograft biopsies were obtained percutaneously using ultrasound guidance processed for light microscopy and immunofluorescence for peritubular capillary staining for C4d. All biopsies were reviewed by a pathologist in a blinded fashion. AMR was diagnosed using standard Banff criteria in combination with graft dysfunction (increase in serum creatinine \>/=0.3 mg/dL over nadir.)
Outcome measures
| Measure |
Eculizumab
n=26 Participants
Patients received eculizumab intravenously according to details provided in the intervention description.
|
|---|---|
|
Number of Subjects With Antibody-Mediated Rejection (AMR) in the First 3 Months After Living Donor Kidney Transplantation
|
2 Participants
|
SECONDARY outcome
Timeframe: 3 monthsHigh DSA levels were defined as B flow cross match channel shift \>350 at any time point in the first 3 months.
Outcome measures
| Measure |
Eculizumab
n=26 Participants
Patients received eculizumab intravenously according to details provided in the intervention description.
|
|---|---|
|
Number of Patients Developing High DSA Levels at Less Than or Equal to 3 Months
|
13 Participants
|
SECONDARY outcome
Timeframe: 1 yearPopulation: 10 subjects discontinued early (\<1 year) according to protocol because they had a B flow cytometric crossmatch (BFMX) \<200.
A splenectomy is a surgical operation involving removal of the spleen. Splenectomy was performed for severe AMR in the setting of a rising serum creatinine (usually \>2.0) and a rising serum DSA level despite daily plasma exchange treatments.
Outcome measures
| Measure |
Eculizumab
n=16 Participants
Patients received eculizumab intravenously according to details provided in the intervention description.
|
|---|---|
|
Number of Patients Requiring Splenectomy
|
0 Participants
|
SECONDARY outcome
Timeframe: 1 month(Maximum serum creatinine-nadir serum creatinine)
Outcome measures
| Measure |
Eculizumab
n=26 Participants
Patients received eculizumab intravenously according to details provided in the intervention description.
|
|---|---|
|
Graft Dysfunction in First Month Post Transplant
|
0.45 mg/dL
Standard Deviation 0.37
|
SECONDARY outcome
Timeframe: up to 15 monthsFollowing the completion of dosing, subjects were to return for follow-up visits at 3 and 6 months post transplant to obtain biopsies and collect follow-up data. Subjects who continued the drug for 12 months were to receive their final assessment at 15 months.
Outcome measures
| Measure |
Eculizumab
n=26 Participants
Patients received eculizumab intravenously according to details provided in the intervention description.
|
|---|---|
|
Length of Follow-up
|
11.9 months
Standard Deviation 6.1
|
SECONDARY outcome
Timeframe: 1 yearPopulation: 10 subjects discontinued early (\<1 year) according to protocol because they had a B flow cytometric crossmatch (BFMX) \<200.
Graft survival means the kidney has not been rejected by the body.
Outcome measures
| Measure |
Eculizumab
n=16 Participants
Patients received eculizumab intravenously according to details provided in the intervention description.
|
|---|---|
|
Number of Subjects With Graft Survival at One Year
|
16 Participants
|
SECONDARY outcome
Timeframe: up to one yearPlasma exchange is needed when there is poor kidney functioning, and donor specific alloantibody (DSA) is high
Outcome measures
| Measure |
Eculizumab
n=26 Participants
Patients received eculizumab intravenously according to details provided in the intervention description.
|
|---|---|
|
Number of Subjects Receiving Posttransplant Plasma Exchange (PE)
|
3 Participants
|
SECONDARY outcome
Timeframe: 1 yearPopulation: 10 subjects discontinued early (\<1 year) according to protocol because they had a B flow cytometric crossmatch (BFMX) \<200. An additional subject did not have a biopsy done at one year.
Transplant glomerulopathy is a morphologic lesion of renal allografts that is characterized histologically by duplication and/or multilayering of the glomerular basement membrane. It is widely accepted as a manifestation of chronic antibody-mediated rejection (AMR). This is determined by histology.
Outcome measures
| Measure |
Eculizumab
n=15 Participants
Patients received eculizumab intravenously according to details provided in the intervention description.
|
|---|---|
|
Transplant Glomerulopathy Incidence at One Year
|
1 Participants
|
Adverse Events
Eculizumab
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Eculizumab
n=26 participants at risk
Patients received eculizumab intravenously according to details provided in the intervention description.
|
|---|---|
|
Renal and urinary disorders
Elevated Creatinine
|
3.8%
1/26 • Number of events 1 • 1 year
|
|
Renal and urinary disorders
Cross-connection end-to-end of the segments of the same ureter
|
3.8%
1/26 • Number of events 1 • 1 year
|
|
Skin and subcutaneous tissue disorders
Swelling and erythema of left hand
|
3.8%
1/26 • Number of events 1 • 1 year
|
|
Cardiac disorders
Atrial Fibrillation
|
15.4%
4/26 • Number of events 4 • 1 year
|
|
Gastrointestinal disorders
Diarrhea and vomiting
|
11.5%
3/26 • Number of events 3 • 1 year
|
|
Cardiac disorders
Rapid pulse
|
3.8%
1/26 • Number of events 1 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Acute dyspnea
|
3.8%
1/26 • Number of events 1 • 1 year
|
|
Blood and lymphatic system disorders
Dissection of the iliac
|
3.8%
1/26 • Number of events 1 • 1 year
|
|
Gastrointestinal disorders
Nausea
|
7.7%
2/26 • 1 year
|
|
General disorders
Headache
|
3.8%
1/26 • Number of events 1 • 1 year
|
|
General disorders
Hypercalcemia
|
3.8%
1/26 • Number of events 1 • 1 year
|
|
General disorders
Tonic-colonic seizure
|
3.8%
1/26 • Number of events 1 • 1 year
|
|
Cardiac disorders
Hypotension
|
3.8%
1/26 • Number of events 1 • 1 year
|
|
Cardiac disorders
Bradycardia
|
3.8%
1/26 • Number of events 1 • 1 year
|
|
General disorders
Tertiary Hyperparathyroidism
|
3.8%
1/26 • Number of events 1 • 1 year
|
|
Injury, poisoning and procedural complications
Wound
|
3.8%
1/26 • Number of events 1 • 1 year
|
|
Injury, poisoning and procedural complications
Small bowel perforation
|
3.8%
1/26 • Number of events 1 • 1 year
|
|
Renal and urinary disorders
Hyperkalemia
|
7.7%
2/26 • Number of events 2 • 1 year
|
|
General disorders
Wound dehiscence
|
7.7%
2/26 • Number of events 2 • 1 year
|
|
General disorders
Fever
|
7.7%
2/26 • Number of events 2 • 1 year
|
|
Cardiac disorders
Hypertension
|
3.8%
1/26 • Number of events 1 • 1 year
|
|
Renal and urinary disorders
Pain following kidney biopsy
|
3.8%
1/26 • Number of events 1 • 1 year
|
|
Infections and infestations
Wound infection
|
3.8%
1/26 • Number of events 1 • 1 year
|
|
Renal and urinary disorders
Acute humoral rejection
|
3.8%
1/26 • Number of events 1 • 1 year
|
|
Injury, poisoning and procedural complications
Ulnar fracture secondary to a dog bite
|
3.8%
1/26 • Number of events 1 • 1 year
|
|
Blood and lymphatic system disorders
Lymphocele
|
3.8%
1/26 • Number of events 1 • 1 year
|
|
Cardiac disorders
Atrial flutter
|
3.8%
1/26 • Number of events 1 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary blastomycosis
|
3.8%
1/26 • Number of events 1 • 1 year
|
|
Renal and urinary disorders
Hematuria
|
3.8%
1/26 • Number of events 1 • 1 year
|
|
Gastrointestinal disorders
Abdominal pain secondary to constipation
|
3.8%
1/26 • Number of events 1 • 1 year
|
|
Renal and urinary disorders
Bleeding following kidney biopsy
|
3.8%
1/26 • Number of events 1 • 1 year
|
|
Infections and infestations
Pneumonia
|
3.8%
1/26 • Number of events 1 • 1 year
|
|
General disorders
Light headed
|
3.8%
1/26 • Number of events 1 • 1 year
|
|
General disorders
Diaphoresis
|
3.8%
1/26 • Number of events 1 • 1 year
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place