Trial Outcomes & Findings for Eculizumab Therapy for Chronic Complement-Mediated Injury in Kidney Transplantation (NCT NCT01327573)

NCT ID: NCT01327573

Last Updated: 2019-08-12

Results Overview

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 16 participants
• Primary outcome timeframe: Baseline
• Results posted on: 2019-08-12

Participant Flow

Participant milestones

Measure	Eculizumab eculizumab will be given in addition to standard immunosuppression regimen (oral tacrolimus or equivalent, MMF \[mycophenolate mofetil \], prednisone) eculizumab: • 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	no Additional Therapy patients in this arm will receive standard immunosuppression regimen (oral tacrolimus or equivalent, MMF, prednisone only, no additional therapy
Overall Study STARTED	11	5
Overall Study Received Treatment/Control as Allocated	10	5
Overall Study COMPLETED	8	4
Overall Study NOT COMPLETED	3	1

Reasons for withdrawal

Measure	Eculizumab eculizumab will be given in addition to standard immunosuppression regimen (oral tacrolimus or equivalent, MMF \[mycophenolate mofetil \], prednisone) eculizumab: • 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	no Additional Therapy patients in this arm will receive standard immunosuppression regimen (oral tacrolimus or equivalent, MMF, prednisone only, no additional therapy
Overall Study Physician Decision	3	1

Baseline Characteristics

Eculizumab Therapy for Chronic Complement-Mediated Injury in Kidney Transplantation

Baseline characteristics by cohort

Measure	Eculizumab n=10 Participants eculizumab will be given in addition to standard immunosuppression regimen (oral tacrolimus or equivalent, MMF \[mycophenolate mofetil \], prednisone) eculizumab: • 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	no Additional Therapy n=5 Participants patients in this arm will receive standard immunosuppression regimen (oral tacrolimus or equivalent, MMF, prednisone only, no additional therapy	Total n=15 Participants Total of all reporting groups
Age, Continuous	38 years n=5 Participants	44 years n=7 Participants	43 years n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Sex: Female, Male Male	7 Participants n=5 Participants	2 Participants n=7 Participants	9 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) White	6 Participants n=5 Participants	2 Participants n=7 Participants	8 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Region of Enrollment United States	10 participants n=5 Participants	5 participants n=7 Participants	15 participants n=5 Participants
C4d Status at Randomization Positive	5 participants n=5 Participants	1 participants n=7 Participants	6 participants n=5 Participants
C4d Status at Randomization Negative	5 participants n=5 Participants	4 participants n=7 Participants	9 participants n=5 Participants
Baseline DSA (Donor Specific Antibody) MFI (mean fluorescent intensity)	5,000 MFI n=5 Participants	3,100 MFI n=7 Participants	4,600 MFI n=5 Participants

PRIMARY outcome

Timeframe: Baseline

Outcome measures

Measure	Eculizumab n=10 Participants eculizumab will be given in addition to standard immunosuppression regimen (oral tacrolimus or equivalent, MMF \[mycophenolate mofetil \], prednisone) eculizumab: • 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	no Additional Therapy n=5 Participants patients in this arm will receive standard immunosuppression regimen (oral tacrolimus or equivalent, MMF, prednisone only, no additional therapy
Baseline eGFR (Estimated Glomerular Filtration Rate)	30.04 mL/min/1.73 m2 Interval 23.77 to 36.31	30.04 mL/min/1.73 m2 Interval 23.77 to 36.31

PRIMARY outcome

Timeframe: Months 2,3,4,5,6

Primary statistical analysis of change from baseline was conducted with mixed effects modeling providing calculated estimates.

Outcome measures

Measure	Eculizumab n=10 Participants eculizumab will be given in addition to standard immunosuppression regimen (oral tacrolimus or equivalent, MMF \[mycophenolate mofetil \], prednisone) eculizumab: • 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	no Additional Therapy n=5 Participants patients in this arm will receive standard immunosuppression regimen (oral tacrolimus or equivalent, MMF, prednisone only, no additional therapy
Estimated Glomerular Filtration Rate (eGFR) at Months 2,3,4,5,6 Month 6	30.21 mL/min/1.73 m2 Interval 25.98 to 34.44	28.69 mL/min/1.73 m2 Interval 22.77 to 34.61
Estimated Glomerular Filtration Rate (eGFR) at Months 2,3,4,5,6 Month 2	29.34 mL/min/1.73 m2 Interval 26.61 to 32.07	31.34 mL/min/1.73 m2 Interval 27.45 to 35.24
Estimated Glomerular Filtration Rate (eGFR) at Months 2,3,4,5,6 Month 3	29.56 mL/min/1.73 m2 Interval 26.56 to 32.55	30.68 mL/min/1.73 m2 Interval 26.43 to 34.93
Estimated Glomerular Filtration Rate (eGFR) at Months 2,3,4,5,6 Month 4	29.78 mL/min/1.73 m2 Interval 26.43 to 33.13	30.02 mL/min/1.73 m2 Interval 25.29 to 34.75
Estimated Glomerular Filtration Rate (eGFR) at Months 2,3,4,5,6 Month 5	29.99 mL/min/1.73 m2 Interval 26.23 to 33.76	29.35 mL/min/1.73 m2 Interval 24.06 to 34.65

PRIMARY outcome

Timeframe: 6 months

Population: These are the between groups percent change that represents the difference between groups when controlling for baseline. Outcome measure #2 provides the data by treatment arm where these data are derived.

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".

Outcome measures

Measure	Eculizumab n=16 Participants eculizumab will be given in addition to standard immunosuppression regimen (oral tacrolimus or equivalent, MMF \[mycophenolate mofetil \], prednisone) eculizumab: • 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	no Additional Therapy patients in this arm will receive standard immunosuppression regimen (oral tacrolimus or equivalent, MMF, prednisone only, no additional therapy
Group Difference Percentage Change in 6-month Estimated Glomerular Filtration Rate (eGFR) Month 2	6.66 percentage change Interval -9.21 to 22.53	—
Group Difference Percentage Change in 6-month Estimated Glomerular Filtration Rate (eGFR) Month 3	3.73 percentage change Interval -13.62 to 21.08	—
Group Difference Percentage Change in 6-month Estimated Glomerular Filtration Rate (eGFR) Month 4	0.80 percentage change Interval -18.52 to 20.12	—
Group Difference Percentage Change in 6-month Estimated Glomerular Filtration Rate (eGFR) Month 5	-2.13 percentage change Interval -23.77 to 19.51	—
Group Difference Percentage Change in 6-month Estimated Glomerular Filtration Rate (eGFR) Month 6	-5.06 percentage change Interval -29.28 to 19.16	—

Adverse Events

Eculizumab

Serious events: 4 serious events

Other events: 2 other events

Deaths: 0 deaths

no Additional Therapy

Serious events: 3 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure	Eculizumab n=10 participants at risk eculizumab will be given in addition to standard immunosuppression regimen (oral tacrolimus or equivalent, MMF \[mycophenolate mofetil \], prednisone) eculizumab: • 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	no Additional Therapy n=5 participants at risk patients in this arm will receive standard immunosuppression regimen (oral tacrolimus or equivalent, MMF, prednisone only, no additional therapy
Renal and urinary disorders Graft Failure	20.0% 2/10 • Number of events 2	20.0% 1/5 • Number of events 1
Infections and infestations Bacterial Infection	10.0% 1/10 • Number of events 1	20.0% 1/5 • Number of events 1
Infections and infestations Viral Infection	10.0% 1/10 • Number of events 1	20.0% 1/5 • Number of events 1

Other adverse events

Measure	Eculizumab n=10 participants at risk eculizumab will be given in addition to standard immunosuppression regimen (oral tacrolimus or equivalent, MMF \[mycophenolate mofetil \], prednisone) eculizumab: • 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	no Additional Therapy n=5 participants at risk patients in this arm will receive standard immunosuppression regimen (oral tacrolimus or equivalent, MMF, prednisone only, no additional therapy
Blood and lymphatic system disorders Anemia	10.0% 1/10 • Number of events 1	0.00% 0/5
Infections and infestations Viral Infection	10.0% 1/10 • Number of events 1	0.00% 0/5

Additional Information

Dr. Sanjay Kulkarni

Yale University

Phone: 203-785-6501

Email: sanjay.kulkarni@yale.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: LTE60