Study of Efficacy and Safety of Bimagrumab in Patients After Hip Fracture Surgery

Mixed Model for Repeated Measures (MMRM) of change from baseline in total LBM (kg) by treatment and visit To assess dose-response relationship of bimagrumab and facilitate an adequate dose selection for future phase III studies, without the need for supportive data from another dose-response finding study, at least three doses were required, ranging from a non-effective or minimally effective dose to a dose where maximal efficacy is expected. Original study was initiated with only two doses of bimagrumab, therefore, a lower dose arm of 70mg has been added to this study with Amendment 2, changing the randomization ratio from 1:1:1 to 2:1:2:2 to either placebo, bimagrumab 70mg, bimagrumab 210mg, or bimagrumab 700mg. Since the 70mg dose was expected to show suboptimal efficacy and fewer patients were randomized to this group, it was used only for dose response modelling and not for hypothesis testing. Consequently, no efficacy evaluations for the bimagrumab 70mg Arm were performed

Mixed Model for Repeated Measures (MMRM) of change from baseline in derived gait speed (m/sec) by treatment and visit

To assess dose-response relationship of bimagrumab and facilitate an adequate dose selection for future phase III studies, without the need for supportive data from another dose-response finding study, at least 3 doses were required, ranging from a non-effective or minimally effective dose to a dose where maximal efficacy is expected. Original study was initiated with only two doses of bimagrumab, therefore, a lower dose arm of 70mg was added to this study with Amendment 2, changing the randomization ratio from 1:1:1 to 2:1:2:2 to either placebo, bimagrumab 70mg, bimagrumab 210mg, or bimagrumab 700mg. Since the 70mg dose was expected to show suboptimal efficacy and fewer patients were randomized to this group, it was used only for dose response modelling and not for hypothesis testing. Consequently, no efficacy evaluations for the bimagrumab 70mg Arm were performed

MMRM change from baseline in total score by treatment & visit to Week 24 in physical performance measured by Short Physical Performance Battery (SPPB) that evaluates lower extremity function. Score range is 0 (worst performance) to 12 (best) to assess dose-response relationship of bimagrumab & facilitate adequate dose selection for future phase III studies, without need for supportive data from another dose-response finding study, at least 3 doses were required, ranging from non- or minimally effective dose to a dose where maximal efficacy was expected. Original study was initiated with only 2 doses, therefore, lower 70mg arm was added to this study, changing randomization ratio from 1:1:1 to 2:1:2:2 to either placebo, bimagrumab 70mg, 210mg, or 700mg. Since 70mg dose was expected to show suboptimal efficacy, fewer patients were randomized to this group & it was used only for dose response modelling & not hypothesis testing. Consequently, no efficacy evaluation for 70mg were performed

Group falls rate

The frequency of having at least one fall up to Week 48 was summarized by treatment groups

Incidence of falls was calculated for each arm up to Week 48. The ratio of these fall rates versus Placebo were calculated and presented as the Falls Rate Ratio. As mentioned in comment 5.1 above, the Falls Rate Ratio for Placebo does not apply because it would entail comparing the group to itself