Atypical Hemolytic Uremic
Conditions
Keywords
atypical hemolytic uremic, aHUS
Brief summary
This is a Phase 3b, open-label, single-arm, multicenter study to evaluate the efficacy and safety of eculizumab in participants with atypical hemolytic uremic syndrome (aHUS) in China
Detailed description
This is a Phase 3b, open-label, single-arm, multicenter study to evaluate the efficacy and safety of eculizumab in participants with aHUS in China. The study will be conducted in participants of any age who weigh ≥ 5 kg and who previously have not been treated with complement inhibitors. The study consists of an up to 7-day Screening Period and a 26-week Treatment Period. An 8-week Safety Follow-up Phone Call will be required only for participants who discontinue eculizumab treatment during the study or for participants who will not receive continued access to eculizumab after completing study treatment. Approximately 25 eligible participants in China will be enrolled.
Interventions
DRUGEculizumab
Weight-based doses of Eculizumab will be administered intravenously as an induction dose followed by maintenance dose at Day 8, 15, or 29 depending on weight; then every 2 or 3 weeks, depending upon weight.
Sponsors
AstraZeneca
Alexion Pharmaceuticals, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
open-label study
Eligibility
Sex/Gender
ALL
Age
0 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
1. Any age weighing ≥ 5 kg 2. Complement treatment naïve with evidence of TMA. 3. History of aHUS prior to kidney transplant,or persistent evidence of TMA at least 4 days after modifying the immunosuppressive regimen. 4. Among participants with onset of TMA postpartum, persistent evidence of TMA for \> 3 days after the day of childbirth 5. All participants must be vaccinated against N meningitidis if not already vaccinated within the time period of active coverage specified by the vaccine manufacturer. 6. Participants \< 18 years of age must have been vaccinated against Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae according to local vaccination schedule guidelines. 7. In participants receiving treatment with medications known to cause TMA, persistent evidence of TMA at least 4 days after modifying the excluded medication
Exclusion criteria
1. Known familial or acquired ADAMTS13deficiency (activity \< 5%). 2. ST-HUS as demonstrated by local guidelines. 3. Positive direct Coombs test which is indicative of a clinically significant immune-mediated hemolysis not due to aHUS. 4. HIV infection, and /or unresolved meningococcal disease 5. Ongoing sepsis, and / or presence or suspicion of active and untreated systemic infection 6. Organ transplantation history, and/or Bone marrow transplant/hematopoietic stem cell transplant within 6 months prior to the start of Screening. 7. Among participants with a kidney transplant, acute kidney dysfunction within 4 weeks of transplant consistent with the diagnosis of acute antibody-mediated rejection. 8. Among participants without a kidney transplant, history of kidney disease other than aHUS 9. Identified drug exposure-related HUS, and / or HUS related to vitamin B12 deficiency and / or known genetic defects of cobalamin C metabolism. 10. History of malignancy within 5 years of Screening. 11. Known systemic sclerosis (scleroderma), systemic lupus erythematosus, or antiphospholipid antibody positivity or syndrome. 12. Chronic dialysis. 13. Prior use of complement inhibitors. 14. Use of tranexamic acid within 7 days prior to the start of Screening. 15. Other immunosuppressive therapies. 16. Receiving chronic intravenous immunoglobulin (IVIg) within 8 weeks prior to the start of Screening. 17. Received vasopressors or inotropes within 7 days prior to Screening. 18. Previously or currently treated with a complement inhibitor. 19. Has participated in another interventional treatment study or used any experimental therapy. 20. Hypersensitivity to any excipient in eculizumab. 21. Pregnant or breastfeeding.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With a Complete Thrombotic Microangiopathy (TMA) Response | Up to Week 26 | The criteria for complete TMA response were: 1. Normalization of platelet count (defined as platelet count ≥ 150000/microliter (ul). 2. Normalization of lactate dehydrogenase (LDH, defined as LDH ≤ upper limit of normal \[ULN\]). 3. ≥ 25% improvement in serum creatinine from baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Serum Concentration of Eculizumab | Pre-dose and post-dose at Days 1, 8, 29, 85, and 141; Pre-dose at Day 183 | — |
| Change From Baseline in Serum Free Complement 5 (C5) | Baseline (Day 1 pre-dose) to Days 1, 8, 29, 85 and 141 (pre-dose and post-dose) and pre-dose at Day 183 | — |
| Change From Baseline in Serum Total C5 | Baseline (Day 1 pre-dose) to Days 1, 8, 29, 85 and 141 (pre-dose and post-dose) and pre-dose at Day 183 | — |
| Number of Participants With an Anti-drug Antibody (ADA) Response | Up to Week 26 | An ADA response was defined as a positive ADA sample at any time during the study. |
| Time to Complete TMA Response | Up to Week 26 | Time to complete TMA response was defined as the time from first infusion to the first time point at which all criteria for complete TMA response was met. The criteria for complete TMA response were: 1. Normalization of platelet count (defined as platelet count ≥ 150000/ul. 2. Normalization of LDH, defined as LDH ≤ ULN). 3. ≥ 25% improvement in serum creatinine from baseline. Participants who did not have a response were censored at the date of last visit or study discontinuation at the time when the analysis was performed. |
| Number of Participants With an Adverse Event (AE) | Up to Week 34 | An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which did not necessarily have a causal relationship with this treatment. A serious AE (SAE) was defined as any untoward medical occurrence that, at any dose: * resulted in death, * was life-threatening, * required inpatient hospitalization or prolongation of existing hospitalization, * resulted in persistent disability/incapacity, * was a congenital anomaly/birth defect, or * was an important medical event. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Adverse Events' Section. |
| Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Each Scheduled Visit | Baseline, Days 22, 43, 71, 99, 113, 127, 155 and 183 | Expressed in milliliters per minute per 1.73 square meters of body surface area. |
| Proportion of Participants With a Chronic Kidney Disease (CKD) Stage Shift Categorized as Improved, Stable, or Worsened at Each Scheduled Visit Compared to Baseline | Baseline to Days 22, 43, 71, 99, 113, 127, 155 and 183 | CKD stage was classified based on the National Kidney Foundation Chronic Kidney Disease Stage where Stage 5 represents the most severe disease and Stage 1 represents the least severe disease. Improved excluded participants with Stage 1 at baseline as there was no room for improvement. Worsened excludes participants with Stage 5 at baseline as there was no room to worsen. |
| Change From Baseline in Platelets | Baseline, Days 22, 43, 71, 99, 113, 127, 155, and 183 | Platelet values obtained from the day of a blood transfusion of platelets through 3 days after the transfusion are excluded from all analysis. |
| Change From Baseline in LDH | Baseline, Days 22, 43, 71, 99, 113, 127, 155, and 183 | — |
| Change From Baseline in Hemoglobin | Baseline, Days 22, 43, 71, 99, 113, 127, 155, and 183 | Hemoglobin values obtained from the day of a blood transfusion of either whole blood or packed red blood cells through 7 days after the transfusion are excluded from all analysis. |
| Proportion of Participants On or Off Dialysis at Each Timepoint | Baseline and Days 22, 43, 71, 99, 113, 127, 155 and 183 | Participants were considered as 'off' dialysis at a specific time point if they were dialysis free for more than 5 days prior to that time point. Participants were considered as 'on' dialysis at a specific time point if they were dialysis free to 5 days or less up prior to that time point. |
Countries
China
Participant flow
Pre-assignment details
After providing informed consent/assent, participants were screened for eligibility for the study during the 7-day Screening Period.
Participants by arm
| Arm | Count |
|---|---|
| Eculizumab Participants received eculizumab as an IV infusion at a dose and schedule according to body weight for 26 weeks. | 25 |
| Total | 25 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Other than specified | 2 |
| Overall Study | Study specific discontinuation criteria | 1 |
Baseline characteristics
| Characteristic | Eculizumab |
|---|---|
| Age, Continuous | 23.40 years STANDARD_DEVIATION 15.95 |
| Age, Customized 85 years and over | 0 Participants |
| Age, Customized Adolescents (12-17 years) | 2 Participants |
| Age, Customized Adults (18-64 years) | 14 Participants |
| Age, Customized Children (2-11 years) | 7 Participants |
| Age, Customized From 65-84 years | 0 Participants |
| Age, Customized Infants and toddlers (28 days-23 months) | 2 Participants |
| Age, Customized In utero | 0 Participants |
| Age, Customized Newborns (0-27 days) | 0 Participants |
| Age, Customized Preterm newborn infants (gestational age < 37 wks) | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 24 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 25 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 25 |
| other Total, other adverse events | 24 / 25 |
| serious Total, serious adverse events | 8 / 25 |
Outcome results
Primary
Percentage of Participants With a Complete Thrombotic Microangiopathy (TMA) Response
The criteria for complete TMA response were: 1. Normalization of platelet count (defined as platelet count ≥ 150000/microliter (ul). 2. Normalization of lactate dehydrogenase (LDH, defined as LDH ≤ upper limit of normal \[ULN\]). 3. ≥ 25% improvement in serum creatinine from baseline.
Time frame: Up to Week 26
Population: Full Analysis Set: Included all participants who received at least 1 dose of study intervention and had at least 1 efficacy assessment post first dose.
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| Eculizumab | Percentage of Participants With a Complete Thrombotic Microangiopathy (TMA) Response | 64.0 percentage of participants | 95% Confidence Interval 42.5 |
Secondary
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Each Scheduled Visit
Expressed in milliliters per minute per 1.73 square meters of body surface area.
Time frame: Baseline, Days 22, 43, 71, 99, 113, 127, 155 and 183
Population: Full Analysis Set: Included all participants who received at least 1 dose of study intervention and had at least 1 efficacy assessment post first dose. 'Number Analyzed' = number of participants evaluable at the specific timepoint. 'Overall number of participants analyzed' = participants evaluable for this outcome measure. 'Number Analyzed' = number of participants evaluable at the specific timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eculizumab | Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Each Scheduled Visit | Day 183 | 36.29 mL/min/1.73^2 | Standard Deviation 44.21 |
| Eculizumab | Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Each Scheduled Visit | Day 22 | 39.82 mL/min/1.73^2 | Standard Deviation 50.83 |
| Eculizumab | Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Each Scheduled Visit | Day 43 | 32.72 mL/min/1.73^2 | Standard Deviation 44.75 |
| Eculizumab | Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Each Scheduled Visit | Day 71 | 40.33 mL/min/1.73^2 | Standard Deviation 47.38 |
| Eculizumab | Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Each Scheduled Visit | Day 99 | 37.53 mL/min/1.73^2 | Standard Deviation 47.17 |
| Eculizumab | Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Each Scheduled Visit | Day 113 | 35.88 mL/min/1.73^2 | Standard Deviation 45.38 |
| Eculizumab | Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Each Scheduled Visit | Day 127 | 35.85 mL/min/1.73^2 | Standard Deviation 48.01 |
| Eculizumab | Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Each Scheduled Visit | Day 155 | 43.33 mL/min/1.73^2 | Standard Deviation 49.32 |
Secondary
Change From Baseline in Hemoglobin
Hemoglobin values obtained from the day of a blood transfusion of either whole blood or packed red blood cells through 7 days after the transfusion are excluded from all analysis.
Time frame: Baseline, Days 22, 43, 71, 99, 113, 127, 155, and 183
Population: Full Analysis Set: Included all participants who received at least 1 dose of study intervention and had at least 1 efficacy assessment post first dose. 'Overall number of participants analyzed' = participants evaluable for this outcome measure. 'Number Analyzed' = number of participants evaluable at the specific timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eculizumab | Change From Baseline in Hemoglobin | Day 22 | 17.0 grams per liter (g/L) | Standard Deviation 18.3 |
| Eculizumab | Change From Baseline in Hemoglobin | Day 43 | 25.7 grams per liter (g/L) | Standard Deviation 20.1 |
| Eculizumab | Change From Baseline in Hemoglobin | Day 71 | 30.5 grams per liter (g/L) | Standard Deviation 22.6 |
| Eculizumab | Change From Baseline in Hemoglobin | Day 99 | 30.3 grams per liter (g/L) | Standard Deviation 19.3 |
| Eculizumab | Change From Baseline in Hemoglobin | Day 113 | 29.8 grams per liter (g/L) | Standard Deviation 17.8 |
| Eculizumab | Change From Baseline in Hemoglobin | Day 127 | 25.2 grams per liter (g/L) | Standard Deviation 16.4 |
| Eculizumab | Change From Baseline in Hemoglobin | Day 155 | 30.5 grams per liter (g/L) | Standard Deviation 14.9 |
| Eculizumab | Change From Baseline in Hemoglobin | Day 183 | 36.2 grams per liter (g/L) | Standard Deviation 15.8 |
Secondary
Change From Baseline in LDH
Time frame: Baseline, Days 22, 43, 71, 99, 113, 127, 155, and 183
Population: Full Analysis Set: Included all participants who received at least 1 dose of study intervention and had at least 1 efficacy assessment post first dose. 'Overall number of participants analyzed' = participants evaluable for this outcome measure. 'Number Analyzed' = number of participants evaluable at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eculizumab | Change From Baseline in LDH | Day 155 | -5.848 microkatal per liter (ukat/L) | Standard Deviation 8.478 |
| Eculizumab | Change From Baseline in LDH | Day 127 | -5.444 microkatal per liter (ukat/L) | Standard Deviation 8.314 |
| Eculizumab | Change From Baseline in LDH | Day 183 | -5.680 microkatal per liter (ukat/L) | Standard Deviation 8.172 |
| Eculizumab | Change From Baseline in LDH | Day 22 | -9.445 microkatal per liter (ukat/L) | Standard Deviation 12.459 |
| Eculizumab | Change From Baseline in LDH | Day 43 | -6.147 microkatal per liter (ukat/L) | Standard Deviation 10.175 |
| Eculizumab | Change From Baseline in LDH | Day 71 | -7.083 microkatal per liter (ukat/L) | Standard Deviation 10.099 |
| Eculizumab | Change From Baseline in LDH | Day 99 | -5.861 microkatal per liter (ukat/L) | Standard Deviation 8.356 |
| Eculizumab | Change From Baseline in LDH | Day 113 | -5.769 microkatal per liter (ukat/L) | Standard Deviation 8.041 |
Secondary
Change From Baseline in Platelets
Platelet values obtained from the day of a blood transfusion of platelets through 3 days after the transfusion are excluded from all analysis.
Time frame: Baseline, Days 22, 43, 71, 99, 113, 127, 155, and 183
Population: Full Analysis Set: Included all participants who received at least 1 dose of study intervention and had at least 1 efficacy assessment post first dose. 'Overall number of participants analyzed' = participants evaluable for this outcome measure. 'Number Analyzed' = number of participants evaluable at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eculizumab | Change From Baseline in Platelets | Day 22 | 76.5 10^9 platelets/liter (L) | Standard Deviation 117.7 |
| Eculizumab | Change From Baseline in Platelets | Day 43 | 65.5 10^9 platelets/liter (L) | Standard Deviation 90.1 |
| Eculizumab | Change From Baseline in Platelets | Day 71 | 71.3 10^9 platelets/liter (L) | Standard Deviation 97.9 |
| Eculizumab | Change From Baseline in Platelets | Day 99 | 79.4 10^9 platelets/liter (L) | Standard Deviation 68.1 |
| Eculizumab | Change From Baseline in Platelets | Day 113 | 60.1 10^9 platelets/liter (L) | Standard Deviation 82.7 |
| Eculizumab | Change From Baseline in Platelets | Day 127 | 61.8 10^9 platelets/liter (L) | Standard Deviation 86.1 |
| Eculizumab | Change From Baseline in Platelets | Day 155 | 76.8 10^9 platelets/liter (L) | Standard Deviation 98.2 |
| Eculizumab | Change From Baseline in Platelets | Day 183 | 80.3 10^9 platelets/liter (L) | Standard Deviation 98 |
Secondary
Change From Baseline in Serum Free Complement 5 (C5)
Time frame: Baseline (Day 1 pre-dose) to Days 1, 8, 29, 85 and 141 (pre-dose and post-dose) and pre-dose at Day 183
Population: Pharmacodynamic (PD) Analysis Set: Included all participants who received at least 1 dose of study intervention and had evaluable PD data. 'Number Analyzed' = number of participants evaluable at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eculizumab | Change From Baseline in Serum Free Complement 5 (C5) | Day 1: Post-dose | -79.8842 ug/mL | Standard Deviation 17.5197 |
| Eculizumab | Change From Baseline in Serum Free Complement 5 (C5) | Day 8: Pre-dose | -79.6539 ug/mL | Standard Deviation 17.8589 |
| Eculizumab | Change From Baseline in Serum Free Complement 5 (C5) | Day 8: Post-dose | -79.6636 ug/mL | Standard Deviation 17.861 |
| Eculizumab | Change From Baseline in Serum Free Complement 5 (C5) | Day 29: Pre-dose | -80.4277 ug/mL | Standard Deviation 17.1241 |
| Eculizumab | Change From Baseline in Serum Free Complement 5 (C5) | Day 29: Post-dose | -80.4284 ug/mL | Standard Deviation 17.1241 |
| Eculizumab | Change From Baseline in Serum Free Complement 5 (C5) | Day 85: Pre-dose | -80.0632 ug/mL | Standard Deviation 17.3489 |
| Eculizumab | Change From Baseline in Serum Free Complement 5 (C5) | Day 85: Post-dose | -80.0632 ug/mL | Standard Deviation 17.3489 |
| Eculizumab | Change From Baseline in Serum Free Complement 5 (C5) | Day 141: Pre-dose | -80.0625 ug/mL | Standard Deviation 17.3485 |
| Eculizumab | Change From Baseline in Serum Free Complement 5 (C5) | Day 141: Post-dose | -80.0632 ug/mL | Standard Deviation 17.3489 |
| Eculizumab | Change From Baseline in Serum Free Complement 5 (C5) | Day 183: Pre-dose | -80.0632 ug/mL | Standard Deviation 17.3489 |
Secondary
Change From Baseline in Serum Total C5
Time frame: Baseline (Day 1 pre-dose) to Days 1, 8, 29, 85 and 141 (pre-dose and post-dose) and pre-dose at Day 183
Population: PD Analysis Set: Included all participants who received at least 1 dose of study intervention and had evaluable PD data. 'Number Analyzed' = number of participants evaluable at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eculizumab | Change From Baseline in Serum Total C5 | Day 1: Post-dose | -12.0267 ug/mL | Standard Deviation 6.1396 |
| Eculizumab | Change From Baseline in Serum Total C5 | Day 8: Pre-dose | 37.9293 ug/mL | Standard Deviation 21.3162 |
| Eculizumab | Change From Baseline in Serum Total C5 | Day 8: Post-dose | 40.2831 ug/mL | Standard Deviation 23.0175 |
| Eculizumab | Change From Baseline in Serum Total C5 | Day 29: Pre-dose | 65.9100 ug/mL | Standard Deviation 25.0734 |
| Eculizumab | Change From Baseline in Serum Total C5 | Day 29: Post-dose | 64.4783 ug/mL | Standard Deviation 22.7695 |
| Eculizumab | Change From Baseline in Serum Total C5 | Day 85: Pre-dose | 71.2418 ug/mL | Standard Deviation 25.735 |
| Eculizumab | Change From Baseline in Serum Total C5 | Day 85: Post-dose | 66.5267 ug/mL | Standard Deviation 26.7232 |
| Eculizumab | Change From Baseline in Serum Total C5 | Day 141: Pre-dose | 71.8284 ug/mL | Standard Deviation 25.3689 |
| Eculizumab | Change From Baseline in Serum Total C5 | Day 141: Post-dose | 67.0693 ug/mL | Standard Deviation 23.1231 |
| Eculizumab | Change From Baseline in Serum Total C5 | Day 183: Pre-dose | 78.5497 ug/mL | Standard Deviation 27.1158 |
Secondary
Mean Serum Concentration of Eculizumab
Time frame: Pre-dose and post-dose at Days 1, 8, 29, 85, and 141; Pre-dose at Day 183
Population: Pharmacokinetic (PK) Analysis Set: Included all participants who received at least 1 dose of study intervention and had evaluable pharmacokinetic data. 'Number Analyzed' = number of participants evaluable at specified timepoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Eculizumab | Mean Serum Concentration of Eculizumab | Day 1: Pre-dose | 4.690 micrograms per milliliter (ug/mL) | Geometric Coefficient of Variation 0 |
| Eculizumab | Mean Serum Concentration of Eculizumab | Day 1: Post-dose | 373.423 micrograms per milliliter (ug/mL) | Geometric Coefficient of Variation 47.59 |
| Eculizumab | Mean Serum Concentration of Eculizumab | Day 8: Pre-dose | 153.190 micrograms per milliliter (ug/mL) | Geometric Coefficient of Variation 69.69 |
| Eculizumab | Mean Serum Concentration of Eculizumab | Day 8: Post-dose | 498.262 micrograms per milliliter (ug/mL) | Geometric Coefficient of Variation 41.18 |
| Eculizumab | Mean Serum Concentration of Eculizumab | Day 29: Pre-dose | 353.726 micrograms per milliliter (ug/mL) | Geometric Coefficient of Variation 36.96 |
| Eculizumab | Mean Serum Concentration of Eculizumab | Day 29: Post-dose | 727.862 micrograms per milliliter (ug/mL) | Geometric Coefficient of Variation 32.22 |
| Eculizumab | Mean Serum Concentration of Eculizumab | Day 85: Pre-dose | 360.070 micrograms per milliliter (ug/mL) | Geometric Coefficient of Variation 43.89 |
| Eculizumab | Mean Serum Concentration of Eculizumab | Day 85: Post-dose | 728.624 micrograms per milliliter (ug/mL) | Geometric Coefficient of Variation 42.04 |
| Eculizumab | Mean Serum Concentration of Eculizumab | Day 141: Pre-dose | 433.737 micrograms per milliliter (ug/mL) | Geometric Coefficient of Variation 41.32 |
| Eculizumab | Mean Serum Concentration of Eculizumab | Day 141: Post-dose | 883.675 micrograms per milliliter (ug/mL) | Geometric Coefficient of Variation 38.74 |
| Eculizumab | Mean Serum Concentration of Eculizumab | Day 183: Pre-dose | 434.739 micrograms per milliliter (ug/mL) | Geometric Coefficient of Variation 38.66 |
Secondary
Number of Participants With an Adverse Event (AE)
An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which did not necessarily have a causal relationship with this treatment. A serious AE (SAE) was defined as any untoward medical occurrence that, at any dose: * resulted in death, * was life-threatening, * required inpatient hospitalization or prolongation of existing hospitalization, * resulted in persistent disability/incapacity, * was a congenital anomaly/birth defect, or * was an important medical event. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Adverse Events' Section.
Time frame: Up to Week 34
Population: Safety Set: Included all participants who received at least 1 dose of study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Eculizumab | Number of Participants With an Adverse Event (AE) | Any AE | 24 Participants |
| Eculizumab | Number of Participants With an Adverse Event (AE) | Any SAE | 8 Participants |
Secondary
Number of Participants With an Anti-drug Antibody (ADA) Response
An ADA response was defined as a positive ADA sample at any time during the study.
Time frame: Up to Week 26
Population: Safety Set: Included all participants who received at least 1 dose of study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Eculizumab | Number of Participants With an Anti-drug Antibody (ADA) Response | 0 Participants |
Secondary
Proportion of Participants On or Off Dialysis at Each Timepoint
Participants were considered as 'off' dialysis at a specific time point if they were dialysis free for more than 5 days prior to that time point. Participants were considered as 'on' dialysis at a specific time point if they were dialysis free to 5 days or less up prior to that time point.
Time frame: Baseline and Days 22, 43, 71, 99, 113, 127, 155 and 183
Population: Full Analysis Set: Included all participants who received at least 1 dose of study intervention and had at least 1 efficacy assessment post first dose. 'Number Analyzed' = number of participants evaluable at specified timepoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Eculizumab | Proportion of Participants On or Off Dialysis at Each Timepoint | Baseline: On Dialysis | 0.440 proportion of participants |
| Eculizumab | Proportion of Participants On or Off Dialysis at Each Timepoint | Day 113: On Dialysis | 0.167 proportion of participants |
| Eculizumab | Proportion of Participants On or Off Dialysis at Each Timepoint | Day 113: Off Dialysis | 0.833 proportion of participants |
| Eculizumab | Proportion of Participants On or Off Dialysis at Each Timepoint | Baseline: Off Dialysis | 0.560 proportion of participants |
| Eculizumab | Proportion of Participants On or Off Dialysis at Each Timepoint | Day 22: On Dialysis | 0.261 proportion of participants |
| Eculizumab | Proportion of Participants On or Off Dialysis at Each Timepoint | Day 22: Off Dialysis | 0.739 proportion of participants |
| Eculizumab | Proportion of Participants On or Off Dialysis at Each Timepoint | Day 43: On Dialysis | 0.235 proportion of participants |
| Eculizumab | Proportion of Participants On or Off Dialysis at Each Timepoint | Day 43: Off Dialysis | 0.765 proportion of participants |
| Eculizumab | Proportion of Participants On or Off Dialysis at Each Timepoint | Day 71: On Dialysis | 0.211 proportion of participants |
| Eculizumab | Proportion of Participants On or Off Dialysis at Each Timepoint | Day 71: Off Dialysis | 0.789 proportion of participants |
| Eculizumab | Proportion of Participants On or Off Dialysis at Each Timepoint | Day 99: On Dialysis | 0.176 proportion of participants |
| Eculizumab | Proportion of Participants On or Off Dialysis at Each Timepoint | Day 99: Off Dialysis | 0.824 proportion of participants |
| Eculizumab | Proportion of Participants On or Off Dialysis at Each Timepoint | Day 127: On Dialysis | 0.111 proportion of participants |
| Eculizumab | Proportion of Participants On or Off Dialysis at Each Timepoint | Day 127: Off Dialysis | 0.889 proportion of participants |
| Eculizumab | Proportion of Participants On or Off Dialysis at Each Timepoint | Day 155: On Dialysis | 0.167 proportion of participants |
| Eculizumab | Proportion of Participants On or Off Dialysis at Each Timepoint | Day 155: Off Dialysis | 0.833 proportion of participants |
| Eculizumab | Proportion of Participants On or Off Dialysis at Each Timepoint | Day 183: On Dialysis | 0.167 proportion of participants |
| Eculizumab | Proportion of Participants On or Off Dialysis at Each Timepoint | Day 183: Off Dialysis | 0.833 proportion of participants |
Secondary
Proportion of Participants With a Chronic Kidney Disease (CKD) Stage Shift Categorized as Improved, Stable, or Worsened at Each Scheduled Visit Compared to Baseline
CKD stage was classified based on the National Kidney Foundation Chronic Kidney Disease Stage where Stage 5 represents the most severe disease and Stage 1 represents the least severe disease. Improved excluded participants with Stage 1 at baseline as there was no room for improvement. Worsened excludes participants with Stage 5 at baseline as there was no room to worsen.
Time frame: Baseline to Days 22, 43, 71, 99, 113, 127, 155 and 183
Population: Full Analysis Set: Included all participants who received at least 1 dose of study intervention and had at least 1 efficacy assessment post first dose. 'Overall number of participants analyzed' = participants evaluable for this outcome measure. 'Number Analyzed' = number of participants evaluable at specified timepoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Eculizumab | Proportion of Participants With a Chronic Kidney Disease (CKD) Stage Shift Categorized as Improved, Stable, or Worsened at Each Scheduled Visit Compared to Baseline | Day 155: Stable | 0.125 proportion of participants |
| Eculizumab | Proportion of Participants With a Chronic Kidney Disease (CKD) Stage Shift Categorized as Improved, Stable, or Worsened at Each Scheduled Visit Compared to Baseline | Day 155: Worsened | 0 proportion of participants |
| Eculizumab | Proportion of Participants With a Chronic Kidney Disease (CKD) Stage Shift Categorized as Improved, Stable, or Worsened at Each Scheduled Visit Compared to Baseline | Day 22: Improved | 0.545 proportion of participants |
| Eculizumab | Proportion of Participants With a Chronic Kidney Disease (CKD) Stage Shift Categorized as Improved, Stable, or Worsened at Each Scheduled Visit Compared to Baseline | Day 22: Stable | 0.455 proportion of participants |
| Eculizumab | Proportion of Participants With a Chronic Kidney Disease (CKD) Stage Shift Categorized as Improved, Stable, or Worsened at Each Scheduled Visit Compared to Baseline | Day 22: Worsened | 0 proportion of participants |
| Eculizumab | Proportion of Participants With a Chronic Kidney Disease (CKD) Stage Shift Categorized as Improved, Stable, or Worsened at Each Scheduled Visit Compared to Baseline | Day 43: Improved | 0.688 proportion of participants |
| Eculizumab | Proportion of Participants With a Chronic Kidney Disease (CKD) Stage Shift Categorized as Improved, Stable, or Worsened at Each Scheduled Visit Compared to Baseline | Day 43: Stable | 0.313 proportion of participants |
| Eculizumab | Proportion of Participants With a Chronic Kidney Disease (CKD) Stage Shift Categorized as Improved, Stable, or Worsened at Each Scheduled Visit Compared to Baseline | Day 43: Worsened | 0 proportion of participants |
| Eculizumab | Proportion of Participants With a Chronic Kidney Disease (CKD) Stage Shift Categorized as Improved, Stable, or Worsened at Each Scheduled Visit Compared to Baseline | Day 71: Improved | 0.722 proportion of participants |
| Eculizumab | Proportion of Participants With a Chronic Kidney Disease (CKD) Stage Shift Categorized as Improved, Stable, or Worsened at Each Scheduled Visit Compared to Baseline | Day 71: Stable | 0.278 proportion of participants |
| Eculizumab | Proportion of Participants With a Chronic Kidney Disease (CKD) Stage Shift Categorized as Improved, Stable, or Worsened at Each Scheduled Visit Compared to Baseline | Day 71: Worsened | 0 proportion of participants |
| Eculizumab | Proportion of Participants With a Chronic Kidney Disease (CKD) Stage Shift Categorized as Improved, Stable, or Worsened at Each Scheduled Visit Compared to Baseline | Day 99: Improved | 0.750 proportion of participants |
| Eculizumab | Proportion of Participants With a Chronic Kidney Disease (CKD) Stage Shift Categorized as Improved, Stable, or Worsened at Each Scheduled Visit Compared to Baseline | Day 99: Stable | 0.250 proportion of participants |
| Eculizumab | Proportion of Participants With a Chronic Kidney Disease (CKD) Stage Shift Categorized as Improved, Stable, or Worsened at Each Scheduled Visit Compared to Baseline | Day 99: Worsened | 0 proportion of participants |
| Eculizumab | Proportion of Participants With a Chronic Kidney Disease (CKD) Stage Shift Categorized as Improved, Stable, or Worsened at Each Scheduled Visit Compared to Baseline | Day 113: Improved | 0.765 proportion of participants |
| Eculizumab | Proportion of Participants With a Chronic Kidney Disease (CKD) Stage Shift Categorized as Improved, Stable, or Worsened at Each Scheduled Visit Compared to Baseline | Day 113: Stable | 0.235 proportion of participants |
| Eculizumab | Proportion of Participants With a Chronic Kidney Disease (CKD) Stage Shift Categorized as Improved, Stable, or Worsened at Each Scheduled Visit Compared to Baseline | Day 113: Worsened | 0 proportion of participants |
| Eculizumab | Proportion of Participants With a Chronic Kidney Disease (CKD) Stage Shift Categorized as Improved, Stable, or Worsened at Each Scheduled Visit Compared to Baseline | Day 127: Improved | 0.765 proportion of participants |
| Eculizumab | Proportion of Participants With a Chronic Kidney Disease (CKD) Stage Shift Categorized as Improved, Stable, or Worsened at Each Scheduled Visit Compared to Baseline | Day 127: Stable | 0.235 proportion of participants |
| Eculizumab | Proportion of Participants With a Chronic Kidney Disease (CKD) Stage Shift Categorized as Improved, Stable, or Worsened at Each Scheduled Visit Compared to Baseline | Day 127: Worsened | 0 proportion of participants |
| Eculizumab | Proportion of Participants With a Chronic Kidney Disease (CKD) Stage Shift Categorized as Improved, Stable, or Worsened at Each Scheduled Visit Compared to Baseline | Day 155: Improved | 0.875 proportion of participants |
| Eculizumab | Proportion of Participants With a Chronic Kidney Disease (CKD) Stage Shift Categorized as Improved, Stable, or Worsened at Each Scheduled Visit Compared to Baseline | Day 183: Improved | 0.824 proportion of participants |
| Eculizumab | Proportion of Participants With a Chronic Kidney Disease (CKD) Stage Shift Categorized as Improved, Stable, or Worsened at Each Scheduled Visit Compared to Baseline | Day 183: Stable | 0.176 proportion of participants |
| Eculizumab | Proportion of Participants With a Chronic Kidney Disease (CKD) Stage Shift Categorized as Improved, Stable, or Worsened at Each Scheduled Visit Compared to Baseline | Day 183: Worsened | 0 proportion of participants |
Secondary
Time to Complete TMA Response
Time to complete TMA response was defined as the time from first infusion to the first time point at which all criteria for complete TMA response was met. The criteria for complete TMA response were: 1. Normalization of platelet count (defined as platelet count ≥ 150000/ul. 2. Normalization of LDH, defined as LDH ≤ ULN). 3. ≥ 25% improvement in serum creatinine from baseline. Participants who did not have a response were censored at the date of last visit or study discontinuation at the time when the analysis was performed.
Time frame: Up to Week 26
Population: Full Analysis Set: Included all participants who received at least 1 dose of study intervention and had at least 1 efficacy assessment post first dose.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Eculizumab | Time to Complete TMA Response | 75.0 days |