Characterization of hemolysis in patients on pegcetacoplan
| Patient . | Study group . | Baseline Hb, g/dL . | Baseline LDH, U/L . | Baseline CH50, U/mL . | ECU starting dose, mg . | Transfusions ≤12 mo before screening . | History of thrombosis . | Study days of hemolysis event/study period . | Hb before hemolysis event∗, g/dL . | Hb during hemolysis event, g/dL . | LDH before hemolysis event∗, U/L . | LDH during hemolysis event, U/L . | Severity/relationship to PEG . | Potential CAC . | Discontinuation . |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | ECU-to-PEG | 8.1 | 279 | 22 | 900 | 0 | No | D315-318/OLP | 12.4 | 10.6 | 214 | 650 | Moderate/not related | Febrile infection | No |
| D318-NR/OLP | 10.6 | 8.8 | 650 | 517 | Severe/not related | Febrile infection | |||||||||
| 2 | PEG-to-PEG | 8.6 | 158 | 0 | 1200 | 0 | No | D49-56/RCP | 10.6 | 8.5†-7.2 | 121 | 1100†-813 | Moderate/related | No | Yes, due to hemolysis |
| 3 | ECU-to-PEG | 8.6 | 228 | 0 | 1200 | 0 | No | D281-309/OLP | 13.3 | 10.4-12.4 | 220 | 658-189 | Moderate/not related | Infection | No |
| 4 | PEG-to-PEG | 9.7 | 197 | 16 | 1200 | 0 | Yes | D242-316/OLP | 14.2 | 6.6-11.3 | 162 | 815-225 | Severe/not related | URT infection | No |
| 5 | PEG-to-PEG | 10.6 | 202 | 20 | 1200 | 2 | No | D140-155/OLP | 15.1 | 13.9-14.5 | 190 | 1050-184 | Severe/not related | Infection | No |
| 6 | PEG-to-PEG | 7.4 | 250 | 3 | 1500 | 2 | Yes | D42-47/RCP | 12.2 | 10.9-6.4 | 149 | 1539-2481† | Moderate/not related | No | Yes, due to hemolysis |
| D47-53/RCP | 12.2 | NR | 1539 | NR | Severe/not related | No | |||||||||
| 7 | ECU-to-PEG | 8.2 | 192 | 33 | 900 | 4 | Yes | D194-NR/FU | 11.1 | NR | 119 | NR | Moderate/not related | No | Yes, due to pneumonitis 20 d before hemolysis |
| 8 | PEG-to-PEG | 6.0 | 317 | 1 | 900 | 5 | No | D36-39/RCP | 10.9 | 7.2†-4.8 | 183 | 4147† | Moderate/related | No | Yes, due to hemolysis |
| 9 | PEG-to-PEG | 7.3 | 301 | 19 | 900 | 5 | Yes | D296-305/OLP | 11.6 | 5.9 | 191 | NR | Severe/not related | COVID infection | Yes, due to COVID-19 infection (fatal) |
| 10 | PEG-to-PEG | 9.0 | 285 | 0 | 1200 | 5 | Yes | D56-224/RCP&OLP | 11.5 | 11.8-9.4 | 373 | 754-883 | Moderate/not related | No | No |
| 11 | PEG-to-PEG | 8.4 | 227 | 0 | 1200 | 5 | No | D225-253/OLP | 11.0 | 10.4-9.7 | 150 | 363-205 | Moderate/not related | URT infection | Yes, due to sepsis |
| D268-289/OLP | 9.7 | NR | 205 | 1133 | Moderate/not related | Sepsis | |||||||||
| 12 | ECU-to-PEG | 8.4 | 236 | 1 | 900 | 6 | No | D149-156/OLP | 13.9 | 6.6 | 113 | NR | Severe/not related | Surgery, sepsis | No |
| D185-245/OLP | 6.0 | 6.4 | 438 | 1184 | Severe/not related | Pneumonia | |||||||||
| 13 | ECU-to-PEG | 10.2 | 1383 | 90 | 900 | 6 | Yes | D191-218/OLP | 13.1 | 6.4 | 173 | 1166 | Moderate/not related | Pancreatitis | No |
| D310-NR/OLP | 11.0 | 9.5‡ | 891 | 2197‡ | Moderate/not related | No | |||||||||
| 14 | ECU-to-PEG | 9.1 | 175 | 4 | 900 | 7 | No | D197-322/OLP | 11.3 | 8.6–11.6 | 207 | 790-222 | Severe/possibly related | No | Yes, due to hemolysis |
| 15 | ECU-to-PEG | 7.9 | 204 | 0 | 1200 | 8 | Yes | D192-199/OLP | 11.9 | 7.3–10 | 98 | 460-505 | Severe/not related | Infection | Yes, due to hemolysis |
| D275-283/OLP | 8.3 | 8.9 | 451 | 840 | Severe/not related | UT infection | |||||||||
| 16 | PEG-to-PEG | 8.9 | 484 | 90 | 1200 | 11 | No | D168-NR/OLP | 8.4 | 8.5 | 524 | 848 | Moderate/not related | Diarrhea | No |
| 17 | ECU-to-PEG | 10.4 | 392 | 12 | 900 | 19 | No | D254-NR/OLP | 7.9 | 9.1 | 323 | 397 | Moderate/not related | No | No |
| 18 | PEG-to-PEG | 8.7 | 426 | 37 | 900 | 21 | Yes | D182-219/OLP | 11.5 | 9.2 | 180 | 246 | Severe/not related | Sepsis | No |
| 19 | PEG-to-PEG | 11.1 | 281 | 27 | 1200 | 30 | No | D106-140/RCP | 12.9 | 7.0-12.1 | 180 | 652-352 | Severe/not related | Vaccination | No |
| D236-NR/OLP | 11.7 | 10.4 | 376 | 2203 | Moderate/not related | No |
| Patient . | Study group . | Baseline Hb, g/dL . | Baseline LDH, U/L . | Baseline CH50, U/mL . | ECU starting dose, mg . | Transfusions ≤12 mo before screening . | History of thrombosis . | Study days of hemolysis event/study period . | Hb before hemolysis event∗, g/dL . | Hb during hemolysis event, g/dL . | LDH before hemolysis event∗, U/L . | LDH during hemolysis event, U/L . | Severity/relationship to PEG . | Potential CAC . | Discontinuation . |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | ECU-to-PEG | 8.1 | 279 | 22 | 900 | 0 | No | D315-318/OLP | 12.4 | 10.6 | 214 | 650 | Moderate/not related | Febrile infection | No |
| D318-NR/OLP | 10.6 | 8.8 | 650 | 517 | Severe/not related | Febrile infection | |||||||||
| 2 | PEG-to-PEG | 8.6 | 158 | 0 | 1200 | 0 | No | D49-56/RCP | 10.6 | 8.5†-7.2 | 121 | 1100†-813 | Moderate/related | No | Yes, due to hemolysis |
| 3 | ECU-to-PEG | 8.6 | 228 | 0 | 1200 | 0 | No | D281-309/OLP | 13.3 | 10.4-12.4 | 220 | 658-189 | Moderate/not related | Infection | No |
| 4 | PEG-to-PEG | 9.7 | 197 | 16 | 1200 | 0 | Yes | D242-316/OLP | 14.2 | 6.6-11.3 | 162 | 815-225 | Severe/not related | URT infection | No |
| 5 | PEG-to-PEG | 10.6 | 202 | 20 | 1200 | 2 | No | D140-155/OLP | 15.1 | 13.9-14.5 | 190 | 1050-184 | Severe/not related | Infection | No |
| 6 | PEG-to-PEG | 7.4 | 250 | 3 | 1500 | 2 | Yes | D42-47/RCP | 12.2 | 10.9-6.4 | 149 | 1539-2481† | Moderate/not related | No | Yes, due to hemolysis |
| D47-53/RCP | 12.2 | NR | 1539 | NR | Severe/not related | No | |||||||||
| 7 | ECU-to-PEG | 8.2 | 192 | 33 | 900 | 4 | Yes | D194-NR/FU | 11.1 | NR | 119 | NR | Moderate/not related | No | Yes, due to pneumonitis 20 d before hemolysis |
| 8 | PEG-to-PEG | 6.0 | 317 | 1 | 900 | 5 | No | D36-39/RCP | 10.9 | 7.2†-4.8 | 183 | 4147† | Moderate/related | No | Yes, due to hemolysis |
| 9 | PEG-to-PEG | 7.3 | 301 | 19 | 900 | 5 | Yes | D296-305/OLP | 11.6 | 5.9 | 191 | NR | Severe/not related | COVID infection | Yes, due to COVID-19 infection (fatal) |
| 10 | PEG-to-PEG | 9.0 | 285 | 0 | 1200 | 5 | Yes | D56-224/RCP&OLP | 11.5 | 11.8-9.4 | 373 | 754-883 | Moderate/not related | No | No |
| 11 | PEG-to-PEG | 8.4 | 227 | 0 | 1200 | 5 | No | D225-253/OLP | 11.0 | 10.4-9.7 | 150 | 363-205 | Moderate/not related | URT infection | Yes, due to sepsis |
| D268-289/OLP | 9.7 | NR | 205 | 1133 | Moderate/not related | Sepsis | |||||||||
| 12 | ECU-to-PEG | 8.4 | 236 | 1 | 900 | 6 | No | D149-156/OLP | 13.9 | 6.6 | 113 | NR | Severe/not related | Surgery, sepsis | No |
| D185-245/OLP | 6.0 | 6.4 | 438 | 1184 | Severe/not related | Pneumonia | |||||||||
| 13 | ECU-to-PEG | 10.2 | 1383 | 90 | 900 | 6 | Yes | D191-218/OLP | 13.1 | 6.4 | 173 | 1166 | Moderate/not related | Pancreatitis | No |
| D310-NR/OLP | 11.0 | 9.5‡ | 891 | 2197‡ | Moderate/not related | No | |||||||||
| 14 | ECU-to-PEG | 9.1 | 175 | 4 | 900 | 7 | No | D197-322/OLP | 11.3 | 8.6–11.6 | 207 | 790-222 | Severe/possibly related | No | Yes, due to hemolysis |
| 15 | ECU-to-PEG | 7.9 | 204 | 0 | 1200 | 8 | Yes | D192-199/OLP | 11.9 | 7.3–10 | 98 | 460-505 | Severe/not related | Infection | Yes, due to hemolysis |
| D275-283/OLP | 8.3 | 8.9 | 451 | 840 | Severe/not related | UT infection | |||||||||
| 16 | PEG-to-PEG | 8.9 | 484 | 90 | 1200 | 11 | No | D168-NR/OLP | 8.4 | 8.5 | 524 | 848 | Moderate/not related | Diarrhea | No |
| 17 | ECU-to-PEG | 10.4 | 392 | 12 | 900 | 19 | No | D254-NR/OLP | 7.9 | 9.1 | 323 | 397 | Moderate/not related | No | No |
| 18 | PEG-to-PEG | 8.7 | 426 | 37 | 900 | 21 | Yes | D182-219/OLP | 11.5 | 9.2 | 180 | 246 | Severe/not related | Sepsis | No |
| 19 | PEG-to-PEG | 11.1 | 281 | 27 | 1200 | 30 | No | D106-140/RCP | 12.9 | 7.0-12.1 | 180 | 652-352 | Severe/not related | Vaccination | No |
| D236-NR/OLP | 11.7 | 10.4 | 376 | 2203 | Moderate/not related | No |
Hemolysis events presented in this table were defined using MedDra preferred terms. Severity of events was defined as follows: mild-events resulted in mild or transient discomfort, not requiring intervention or treatment, and not limiting or interfering with daily activities; moderate-events are sufficiently discomforting to limit or interfere with daily activities and may require interventional treatment; severe-event results in significant symptoms that prevent normal daily activities and may require hospitalization or invasive intervention. Severity of hemolysis event and relationship to study drug are based on investigator report. Hemoglobin limit ranges are 12.0 to 16.0 g/dL for female participants and 13.6 to 18.0 g/dL for male participants; LDH limit range is 113 to 226 U/L.
CAC, complement-amplifying condition; CH50, total complement function; D, day; ECU, eculizumab; Hb, hemoglobin; LDH, lactate dehydrogenase; NR, not reported; OLP, open-label period; PEG, pegcetacoplan; RCP, randomized controlled period; URT, upper respiratory tract; UT, urinary tract.
Most recent available measurement before event.
Values recorded by a local laboratory.
In patient 13, these “during event” laboratory values were recorded 1 day before the reported start date of the AE of hemolysis, but were deemed the most appropriate measurements to use.