Extended Data Fig. 6: Parts B and C – Study design.
From: High-dose nusinersen for spinal muscular atrophy: a phase 3 randomized trial
DEVOTE was powered to assess the efficacy of the 50/28 mg regimen in infantile-onset participants as compared to a prespecified matched sham group from ENDEAR. Inclusion of the 12/12 mg dosing regimen in Part B was intended to provide supportive evidence, but the study was not sufficiently powered to detect statistically significant differences between the 50/28 mg and 12/12 mg groups. aA prespecified hierarchical testing procedure was used for the primary and secondary endpoints for Part B infantile-onset (see Extended Data Table 2). bENDEAR matched sham, CHERISH matched sham and CHERISH matched 12/12 mg indicate prespecified subsets of participants matched to characteristics of the DEVOTE 50/28 mg group (see Extended Data Table 2). CHOP-INTEND, Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders; EFS, event-free survival; HFMSE, Hammersmith Functional Motor Scale Expanded; HINE-2, Hammersmith Infant Neurological Exam section 2; NfL, neurofilament light chain; OS, overall survival; RULM, Revised Upper Limb Module; SMA, spinal muscular atrophy; SMN2, survival motor neuron 2.
