Stage V Chronic Kidney Disease
Conditions
Brief summary
Primary Objective: To evaluate the safety and potential efficacy of eculizumab to prevent AMR in sensitized recipients of deceased donor kidney transplants.
Interventions
DRUGEculizumab
Sponsors
Alexion Pharmaceuticals, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female participants ≥18 years old. 2. Participants with Stage V chronic kidney disease who received a kidney transplant from a deceased donor to whom they were sensitized. 3. History of prior exposure to HLA (human leukocyte antigen): * Prior solid organ or tissue allograft * Pregnancy * Blood transfusion * Prior exposure to specific donor's HLA
Exclusion criteria
1. Has received treatment with eculizumab at any time prior to enrolling in this study. 2. Blood type (A, B, and O blood glycoproteins-blood type) incompatible with deceased donor. 3. History of severe cardiac disease. 4. Prior splenectomy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Post-transplantation Treatment Failure In The First 9 Weeks Post Transplantation | Baseline, Week 9 | Results are reported for post-transplantation treatment failure and composite endpoints, defined as the occurrence of biopsy-proven acute antibody-mediated rejection (AMR), graft loss, death, or loss to follow-up (including discontinuation) in the first 9 weeks post transplantation. The diagnosis of acute AMR (occurring within the first 9 weeks post transplantation) was based on kidney allograft dysfunction and a biopsy performed due to suspected rejection, proteinuria, increased serum creatinine, or acute tubular necrosis. Treatment failure was the occurrence of at least 1 of the composite endpoint components by Week 9 post transplantation. A participant experiencing multiple events was only counted once for the composite endpoint. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Cumulative Incidence Function (CIF) Of Other Adverse Events (AEs) Of Interest At Month 12 | Baseline, Month 12 | Specific analyses of other AEs of interest that occurred at Month 12 included cumulative incidence of clinically significant infection (CSI); post-transplant lymphoproliferative disease (PTLD); malignancies; biopsy-proven acute cellular rejection (ACR) of any grade meeting Banff 2007 criteria; allograft loss for reasons other than AMR. CSIs were defined as infections (confirmed by culture, biopsy, genomic, or serologic findings) that required hospitalization or anti-infective treatment, or otherwise deemed significant by the Investigator. CSI subcategories of interest included cytomegalovirus (CMV) disease; BK virus disease; encapsulated bacterial infection; fungal infections; aspergillus infections. Results are reported as CIF, where a larger CIF indicates a higher incidence of an AE, and were calculated using Statistical Analysis System software and macro CIF. A summary of serious and all other non-serious AEs regardless of causality is located in the Reported Adverse Events module. |
| Participants That Developed Severe ACR (Other AE Of Interest) At Month 12 | Baseline, Month 12 | This outcome measure focuses on the other AE of interest, severe ACR, which occurred at Month 12. It pertains specifically to the number of participants who developed severe ACR that did not respond to thymoglobulin or other lymphocyte-depleting agents. A summary of serious and all other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module. |
Countries
Australia, France, Italy, Spain, Sweden, United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Eculizumab All eculizumab was administered IV over 25 to 45 minutes. Eculizumab 1200 mg was administered approximately 1 hour prior to kidney allograft reperfusion.
Eculizumab 900 mg was administered IV over 25 to 45 minutes on post-transplantation Days 1 and 7, and on post-transplantation Days 14, 21, and 28, plus or minus 2 days.
Eculizumab 1200 mg was administered IV over 25 to 45 minutes on post-transplantation Days 35, 49, and 63, plus or minus 2 days. | 80 |
| Total | 80 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 6 |
| Overall Study | Death | 6 |
| Overall Study | Graft loss | 2 |
| Overall Study | Lost to Follow-up | 3 |
| Overall Study | Renal transplantectomy | 1 |
| Overall Study | Returned to chronic dialysis | 1 |
| Overall Study | Terminal chronic kidney dysfunction | 1 |
Baseline characteristics
| Characteristic | Eculizumab |
|---|---|
| Age, Continuous | 50.7 years STANDARD_DEVIATION 11.26 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants |
| Race/Ethnicity, Customized Asian | 5 Participants |
| Race/Ethnicity, Customized Black or African American | 7 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race/Ethnicity, Customized Unknown or Not Reported | 9 Participants |
| Race/Ethnicity, Customized White | 59 Participants |
| Sex: Female, Male Female | 48 Participants |
| Sex: Female, Male Male | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 6 / 80 |
| other Total, other adverse events | 80 / 80 |
| serious Total, serious adverse events | 70 / 80 |
Outcome results
Primary
Post-transplantation Treatment Failure In The First 9 Weeks Post Transplantation
Results are reported for post-transplantation treatment failure and composite endpoints, defined as the occurrence of biopsy-proven acute antibody-mediated rejection (AMR), graft loss, death, or loss to follow-up (including discontinuation) in the first 9 weeks post transplantation. The diagnosis of acute AMR (occurring within the first 9 weeks post transplantation) was based on kidney allograft dysfunction and a biopsy performed due to suspected rejection, proteinuria, increased serum creatinine, or acute tubular necrosis. Treatment failure was the occurrence of at least 1 of the composite endpoint components by Week 9 post transplantation. A participant experiencing multiple events was only counted once for the composite endpoint.
Time frame: Baseline, Week 9
Population: Full Analysis Population: participants who were enrolled, received a deceased donor kidney transplant, and received at least 1 dose of eculizumab.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Eculizumab | Post-transplantation Treatment Failure In The First 9 Weeks Post Transplantation | Treatment Failure - Yes | 7 Participants |
| Eculizumab | Post-transplantation Treatment Failure In The First 9 Weeks Post Transplantation | Treatment Failure - No | 73 Participants |
| Eculizumab | Post-transplantation Treatment Failure In The First 9 Weeks Post Transplantation | Biopsy-proven Acute AMR | 3 Participants |
| Eculizumab | Post-transplantation Treatment Failure In The First 9 Weeks Post Transplantation | Graft Loss | 4 Participants |
| Eculizumab | Post-transplantation Treatment Failure In The First 9 Weeks Post Transplantation | Death | 1 Participants |
| Eculizumab | Post-transplantation Treatment Failure In The First 9 Weeks Post Transplantation | Lost to Follow-up (Including Discontinuation) | 1 Participants |
Comparison: Analysis of post-transplantation treatment failure ratep-value: <0.001Exact binomial test
Other Pre-specified
Cumulative Incidence Function (CIF) Of Other Adverse Events (AEs) Of Interest At Month 12
Specific analyses of other AEs of interest that occurred at Month 12 included cumulative incidence of clinically significant infection (CSI); post-transplant lymphoproliferative disease (PTLD); malignancies; biopsy-proven acute cellular rejection (ACR) of any grade meeting Banff 2007 criteria; allograft loss for reasons other than AMR. CSIs were defined as infections (confirmed by culture, biopsy, genomic, or serologic findings) that required hospitalization or anti-infective treatment, or otherwise deemed significant by the Investigator. CSI subcategories of interest included cytomegalovirus (CMV) disease; BK virus disease; encapsulated bacterial infection; fungal infections; aspergillus infections. Results are reported as CIF, where a larger CIF indicates a higher incidence of an AE, and were calculated using Statistical Analysis System software and macro CIF. A summary of serious and all other non-serious AEs regardless of causality is located in the Reported Adverse Events module.
Time frame: Baseline, Month 12
Population: Safety Population: enrolled participants who received at least 1 dose of eculizumab.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Eculizumab | Cumulative Incidence Function (CIF) Of Other Adverse Events (AEs) Of Interest At Month 12 | Confirmed CSI | 0.7989 Proportion of Adverse Events |
| Eculizumab | Cumulative Incidence Function (CIF) Of Other Adverse Events (AEs) Of Interest At Month 12 | CMV Infection | 0.2994 Proportion of Adverse Events |
| Eculizumab | Cumulative Incidence Function (CIF) Of Other Adverse Events (AEs) Of Interest At Month 12 | BK Virus Infection | 0.1536 Proportion of Adverse Events |
| Eculizumab | Cumulative Incidence Function (CIF) Of Other Adverse Events (AEs) Of Interest At Month 12 | Encapsulated Bacterial Infection | 0.1642 Proportion of Adverse Events |
| Eculizumab | Cumulative Incidence Function (CIF) Of Other Adverse Events (AEs) Of Interest At Month 12 | Fungal Infection | 0.1287 Proportion of Adverse Events |
| Eculizumab | Cumulative Incidence Function (CIF) Of Other Adverse Events (AEs) Of Interest At Month 12 | Aspergillus Infection | 0 Proportion of Adverse Events |
| Eculizumab | Cumulative Incidence Function (CIF) Of Other Adverse Events (AEs) Of Interest At Month 12 | PTLD | 0.0264 Proportion of Adverse Events |
| Eculizumab | Cumulative Incidence Function (CIF) Of Other Adverse Events (AEs) Of Interest At Month 12 | Malignancies | 0.0264 Proportion of Adverse Events |
| Eculizumab | Cumulative Incidence Function (CIF) Of Other Adverse Events (AEs) Of Interest At Month 12 | Biopsy-proven ACR | 0.0375 Proportion of Adverse Events |
| Eculizumab | Cumulative Incidence Function (CIF) Of Other Adverse Events (AEs) Of Interest At Month 12 | Allograft Loss For Reasons Other Than AMR | 0.1132 Proportion of Adverse Events |
Other Pre-specified
Participants That Developed Severe ACR (Other AE Of Interest) At Month 12
This outcome measure focuses on the other AE of interest, severe ACR, which occurred at Month 12. It pertains specifically to the number of participants who developed severe ACR that did not respond to thymoglobulin or other lymphocyte-depleting agents. A summary of serious and all other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.
Time frame: Baseline, Month 12
Population: Safety Population: participants who received at least 1 dose of eculizumab.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Eculizumab | Participants That Developed Severe ACR (Other AE Of Interest) At Month 12 | 3 Participants |