Study of Ravulizumab in Pediatric Participants With HSCT-TMA

The criteria for TMA response were: 1. Normalization of platelet count (defined as platelet count ≥ 50000 mm^3 or >=50% increase in platelet count) without transfusion support during the prior 7 days. 2. Normalization of lactate dehydrogenase (LDH, defined as LDH ≤ upper limit of normal [ULN]) and absence of schistocytes. 3. At least 50% reduction in protein/creatinine ratio from baseline. Participants must meet each TMA criterion at 2 separate assessments obtained at least 24 hours apart, with no criteria failures or more than 1 missed scheduled visit in between. Additionally, all intervals in which the criteria were met must overlap for at least 1 day.

Time to TMA response was defined as the time from first infusion to the first time point at which all criteria for TMA response was met. Participants were assigned as responders at the time of their TMA response and were censored at the earlier of last assessment with all 3 TMA response components available (including measurements collected after treatment discontinuation), or death if they did not respond by then. TMA response required the following: 1. Normalization of platelet count (defined as platelet count ≥ 50000 mm^3 or >=50% increase in platelet count) without transfusion support during the prior 7 days. 2. Normalization of LDH (defined as LDH ≤ULN) and absence of schistocytes. 3. At least 50% reduction in protein/creatinine ratio from baseline.

Hematologic response required the following: (1) Normalization of platelet count (defined as platelet count ≥ 50000 mm^3 or >=50% increase in platelet count) without transfusion support during the prior 7 days and (2) Normalization of LDH (defined as LDH ≤ULN) and absence of schistocytes.

Time to Hematologic response was defined as the time from first infusion to the first time point at which all criteria for hematologic response was met. Participants were assigned as responders at the time of their response and were censored at their discontinuation time or at the end of available follow-up if they did not respond by then. Hematologic response required the following: (1) Normalization of platelet count (defined as platelet count ≥ 50000 mm^3 or >=50% increase in platelet count) without transfusion support during the prior 7 days and (2) Normalization of LDH (defined as LDH ≤ULN) and absence of schistocytes.

Hemoglobin response was defined as the ability to maintain hemoglobin ≥ 10 g/dL without RBC transfusion support. The criterion must have been met at 2 separate assessments obtained at least 24 hours apart, and any measurement in between, and without RBC transfusion support during the prior 7 days.

Normalization of platelet count was defined as baseline platelet count ≤ 50000 mm^3 or > 50000 mm^3, absolute platelet count > 50000 mm^3 or >=50% increase in platelet count without transfusion support during the prior 7 days.

Partial response was defined as a participant meeting at least 1, but not all, criteria for TMA response. TMA response required the following: 1. Normalization of platelet count (defined as platelet count ≥ 50000 mm^3 or >=50% increase in platelet count) without transfusion support during the prior 7 days. 2. Normalization of LDH, (defined as LDH ≤ULN) and absence of schistocytes. 3. At least 50% reduction in protein/creatinine ratio from baseline.

Loss of response occurred when a participant who had previously achieved a TMA response failed to meet criteria for one or more components of TMA response at a subsequent visit in treatment period. At least one parameter must fail to meet response criteria at 2 separate assessments obtained at least 24 hours apart, and any measurement in between. TMA response required the following: 1. Normalization of platelet count (defined as platelet count ≥ 50000 mm^3 or >=50% increase in platelet count) without transfusion support during the prior 7 days. 2. Normalization of LDH (defined as LDH ≤ULN) and absence of schistocytes. 3. At least 50% reduction in protein/creatinine ratio from baseline.

This analysis includes data for each participant after TMA response through final follow-up. Participants with TMA response who do not experience these events are censored at their end of study date. TMA response required following: 1. Normalization of platelet count (defined as platelet count ≥ 50000 mm^3 or >=50% increase in platelet count) without transfusion support during the prior 7 days. 2. Normalization of LDH (defined as LDH ≤ULN) and absence of schistocytes. 3. At least 50% reduction in protein/creatinine ratio from baseline. The estimate is calculated based on Kaplan-Meier method.

For participants that meet criteria for TMA response during 26-week Treatment Period, TMA relapse is defined as evidence of worsening hematologic and renal dysfunction due to TMA during post-treatment Follow-up Period that requires treatment intervention, as determined by Investigator. TMA response required the following: 1. Normalization of platelet count (defined as platelet count ≥ 50000 mm^3 or >=50% increase in platelet count) without transfusion support during the prior 7 days. 2. Normalization of LDH (defined as LDH ≤ULN) and absence of schistocytes. 3. At least 50% reduction in protein/creatinine ratio from baseline.

The Kaplan-Meier method was used to measure overall survival estimate. Overall survival was calculated from date of treatment start to date of a documented death event (death due to any cause) or date of censoring. Participants who survived were censored at the earliest of an additional hematopoietic stem cell transplant (HSCT), Week 52, or their last known date alive.

Cumulative incidence was estimated using a competing risk model. Non-relapse mortality was defined as a participant's death due to any cause during the study, with the exception of death due to underlying disease progression or relapse.