A Phase 1 interventional study of eculizumab in Kidney; Complications, Allograft, sponsored by Sanjay Kulkarni. Completed at 1 site in United States. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2019-08-12.
Sponsored by Sanjay Kulkarni · Phase 1, Interventional, and Treatment
This study is designed to assess the effectiveness of eculizumab in recipients of kidney transplantation with donor-specific antibodies (DSA) and worsening kidney function and to assess if eculizumab improves endothelial cell injury in the kidney.
The investigators hypothesize that complement inhibition with eculizumab will reduce allograft injury, resulting from less complement-mediated injury of endothelial cells and less endothelial cell activation.
This study will address the clinical challenge that currently exists in the management of kidney transplant recipients who have developed de novo DSA, have deteriorating graft function, yet have no established treatment alternative.
This is a randomized, open-label, pilot intervention trial. Post transplant patients with deteriorating renal function (defined as 20% reduction in GFR) will be screened for the development of DSA and biopsied for the presence of C4d deposition. All patients with DSA and those meeting inclusion/exclusion criteria will undergo protocol renal biopsy and will be assessed for C4d deposition. Participants will be randomized to treatment with eculizumab plus standard of care (SOC) or SOC only. Randomization will be stratified by C4d status (C4d+/C4d-) with 10 subjects (7 eculizumab, 3 SOC only) in each stratum.
Eculizumab is an antibody that has been developed to inhibit the complement protein C5. Eculizumab will be delivered via IV according to the following schedule:
This is the only study on the registry with Sanjay Kulkarni as lead sponsor.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
eculizumab will be given in addition to standard immunosuppression regimen (oral tacrolimus or equivalent, MMF \[mycophenolate mofetil \], prednisone)
Drug: eculizumab
patients in this arm will receive standard immunosuppression regimen (oral tacrolimus or equivalent, MMF, prednisone only, no additional therapy
* Eculizumab Induction 600mg IV every 7 days for 4 doses * Eculizumab 900mg IV 7 days later * Eculizumab Maintenance 900mg IV every 14 days for total of 26 weeks
Also known as: h5G1.1-mAb, Soliris
Baseline eGFR (Estimated Glomerular Filtration Rate)
Time frame: Baseline
Estimated Glomerular Filtration Rate (eGFR) at Months 2,3,4,5,6
Primary statistical analysis of change from baseline was conducted with mixed effects modeling providing calculated estimates.
Time frame: Months 2,3,4,5,6
Group Difference Percentage Change in 6-month Estimated Glomerular Filtration Rate (eGFR)
These data were calculated by mean 6-month eGFR minus baseline mean eGFR divided by baseline eGFR. Presented below are the between groups results. These results were derived from the results in the outcome "Estimated Glomerular Filtration Rate (eGFR) at Months 2,3,4,5,6".
Time frame: 6 months
| Milestone | Eculizumab | no Additional Therapy |
|---|---|---|
| Started | 11 | 5 |
| Received treatment/control as allocated | 10 | 5 |
| Completed | 8 | 4 |
| Not completed | 3 | 1 |
| Withdrew: Physician decision | 3 | 1 |
| mL/min/1.73 m2 | Eculizumab | no Additional Therapy |
|---|---|---|
| Baseline eGFR (Estimated Glomerular Filtration Rate) | 30.04 (23.77 to 36.31) | 30.04 (23.77 to 36.31) |
Primary statistical analysis of change from baseline was conducted with mixed effects modeling providing calculated estimates.
| mL/min/1.73 m2 | Eculizumab | no Additional Therapy |
|---|---|---|
| Month 2 | 29.34 (26.61 to 32.07) | 31.34 (27.45 to 35.24) |
| Month 3 | 29.56 (26.56 to 32.55) | 30.68 (26.43 to 34.93) |
| Month 4 | 29.78 (26.43 to 33.13) | 30.02 (25.29 to 34.75) |
| Month 5 | 29.99 (26.23 to 33.76) | 29.35 (24.06 to 34.65) |
| Month 6 | 30.21 (25.98 to 34.44) | 28.69 (22.77 to 34.61) |
These data were calculated by mean 6-month eGFR minus baseline mean eGFR divided by baseline eGFR. Presented below are the between groups results. These results were derived from the results in the outcome "Estimated Glomerular Filtration Rate (eGFR) at Months 2,3,4,5,6".
| percentage change | Between Groups Difference |
|---|---|
| Month 2 | 6.66 (-9.21 to 22.53) |
| Month 3 | 3.73 (-13.62 to 21.08) |
| Month 4 | 0.80 (-18.52 to 20.12) |
| Month 5 | -2.13 (-23.77 to 19.51) |
| Month 6 | -5.06 (-29.28 to 19.16) |
Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Eculizumab | — | 4/10 (40%) | 2/10 (20%) |
| no Additional Therapy | — | 3/5 (60%) | 0/5 (0%) |
| Event | Eculizumab | no Additional Therapy |
|---|---|---|
| Graft FailureRenal and urinary disorders | 2/10 | 1/5 |
| Bacterial InfectionInfections and infestations | 1/10 | 1/5 |
| Viral InfectionInfections and infestations | 1/10 | 1/5 |
| Event | Eculizumab | no Additional Therapy |
|---|---|---|
| AnemiaBlood and lymphatic system disorders | 1/10 | 0/5 |
| Viral InfectionInfections and infestations | 1/10 | 0/5 |
| Age, Continuous(years) | Eculizumab | no Additional Therapy | Total |
|---|---|---|---|
| Median | 38 (20 to 57) | 44 (33 to 65) | 43 (20 to 65) |
| Sex: Female, Male(Participants) | Eculizumab | no Additional Therapy | Total |
|---|---|---|---|
| Female | 3 | 3 | 6 |
| Male | 7 | 2 | 9 |
| Race (NIH/OMB)(Participants) | Eculizumab | no Additional Therapy | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 1 | 2 | 3 |
| White | 6 | 2 | 8 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 3 | 1 | 4 |
| Region of Enrollment(participants) | Eculizumab | no Additional Therapy | Total |
|---|---|---|---|
| United States | 10 | 5 | 15 |
| C4d Status at Randomization(participants) | Eculizumab | no Additional Therapy | Total |
|---|---|---|---|
| Positive | 5 | 1 | 6 |
| Negative | 5 | 4 | 9 |
| Baseline DSA (Donor Specific Antibody) MFI (mean fluorescent intensity)(MFI) | Eculizumab | no Additional Therapy | Total |
|---|---|---|---|
| Median | 5,000 (2,900 to 13,400) | 3,100 (1,100 to 6,000) | 4,600 (1,100 to 13,400) |
This study is completed, as verified in Jul 2019. You cannot join it, but the record below documents what was studied.
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