A Phase 2 Study to Evaluate the Efficacy and Safety of AMG531 in Aplastic Anemia

The proportion of subjects achieving a platelet response at Week 9, and two-sided 95% confidence interval will be calculated. Platelet response is defined as 1) achieving absolute platelet increase of ≥ 20x10\^9/L above baseline or 2) increase to ≥ 10x10\^9/L and by at least 100% from baseline.

Time frame: At week 9

Population: All efficacy analyses were carried out using the Per Protocol Set, which was defined as all enrolled subjects who received ≥6 times of the specified dose, with no major violation in the initial dose evaluation period. The Overall Number of Participants Analyzed is not consistent with numbers provided in the Participant Flow module because the Participant Flow module has been recorded based on the Full Analysis Set.

For subjects with a platelet response in any time, time to the initial platelet response and duration of platelet response will be summarized Time to the initial platelet response will be calculated as sampling date (response achieved) minus first dose date of study drug plus 1. Duration of platelet response will be calculated as the maximum of the duration of platelet response for each subject, each duration of response calculated as the date when response is disappeared minus the date when response is achieved. The censoring date is defined as the date of the last Platelet examination or EOS whichever archives first.

Time frame: Initial dose evaluation period (Week 9), Week 12, Week 16, Week 24, Week 52, Week 104, and Week 156

Population: A total of 29 subjects achieved a platelet response and the median duration of the platelet response was 77.0 days (range: 5 to 959 days). For the 29 subjects who achieved a platelet response, the median time to the initial platelet response was 43 days (range: 8 to 219 days).

The longest duration of study drug discontinuation in subjects while maintaining a stable response is summarized

Time frame: Initial dose evaluation period (Week 9), Week 12, Week 16, Week 24, Week 52, Week 104, and Week 156

Population: 3/33 (9.1%) subjects (who maintained blood cell response) discontinued the study drug during Week 1 to Week 156.

The proportion of subjects with a platelet response in any time during the initial dose evaluation period, Week 1 through Week 12, Week 1 through Week 16, Week 1 through Week 24, Week 1 through Week 52, Week 1 through Week 104 and Week 1 through Week 156.

Time frame: Initial dose evaluation period (Week 9), Week 12, Week 16, Week 24, Week 52, Week 104, and Week 156

Population: All efficacy analyses were carried out using the Per Protocol Set, which was defined as all enrolled subjects who received ≥6 times of the specified dose, with no major violation in the initial dose evaluation period. The Overall Number of Participants Analyzed is not consistent with numbers provided in the Participant Flow module because the Participant Flow module has been recorded based on the Full Analysis Set.

The proportion of subjects with erythroid response, neutrophil response and erythroid and/or neutrophil response in any time during the initial dose evaluation period, Week 1 through Week 12, Week 1 through Week 16, Week 1 through Week 24, Week 1 through Week 52, Week 1 through Week 104, and Week1 through Week 156 will be calculated in the same manner as the primary variables (The number of subjects discontinued or subjects who have missing data will not be calculated).

Time frame: Initial dose evaluation period (Week 9), Week 12, Week 16, Week 24, Week 52, Week 104, and Week 156

Population: All efficacy analyses were carried out using the Per Protocol Set, which was defined as all enrolled subjects who received ≥6 times of the specified dose, with no major violation in the initial dose evaluation period. The Overall Number of Participants Analyzed is not consistent with numbers provided in the Participant Flow module because the Participant Flow module has been recorded based on the Full Analysis Set.

The proportion of subjects achieving platelet transfusion independency in any time during the initial dose evaluation period , Week 1 through Week 12, Week 1 through Week 16, Week 1 through Week 24, Week 1 through Week 52, Week 1 through Week 104, and Week1 through Week 156 will be calculated in the same manner as the primary variables (The number of subjects discontinued or subjects who have missing data will not be calculated). Platelet transfusion independence is defined as achieving transfusion free period of at least 8 consecutive weeks (56 days).

Time frame: Initial dose evaluation period (Week 9), Week 12, Week 16, Week 24, Week 52, Week 104, and Week 156

Population: With respcet to platelet transfusion indendpendence, the proportion will be calculated based on all subjcets in each analysis set and all subjects receving platelet transfusion as a pretreatment 8 weeks prior to the first AMG531 administration respectively.

Tri-lineage response is defined in those achieving platelet response, erythroid response, and neutrophil response all together. The proportion of subjects with tri-lineage response will be calculated in the same manner as the primary variables. Time to tri-lineage response will be summarized in the same manner as time to platelet response. Time to tri-lineage response is defined as duration of the time from Day 1 to the date of platelet response, erythroid response or neutrophil response whichever achieves last in Visit.

Time frame: Initial dose evaluation period (Week 9), Week 12, Week 16, Week 24, Week 52, Week 104, and Week 157

Population: All efficacy analyses were carried out using the Per Protocol Set, which was defined as all enrolled subjects who received ≥6 times of the specified dose, with no major violation in the initial dose evaluation period. The Overall Number of Participants Analyzed is not consistent with numbers provided in the Participant Flow module because the Participant Flow module has been recorded based on the Full Analysis Set.