CHERISH
(2018)Objective
To evaluate the efficacy and safety of intrathecal nusinersen versus a sham procedure in children with later-onset spinal muscular atrophy (SMA).
Study Summary
• Multicenter, double-blind, sham-controlled phase 3 trial (N=126; 2:1 nusinersen vs sham) in children (2–12 yr) with later-onset SMA (symptom onset after 6 mo). • Primary endpoint (least-squares mean change in HFMSE at month 15): interim analysis showed +4.0 vs −1.9 (difference 5.9 points, 95% CI 3.7–8.1; P<0.001), prompting early trial termination. • Final analysis: +3.9 vs −1.0 (difference 4.9 points, 95% CI 3.1–6.7). • 57% of nusinersen vs 26% of sham had ≥3-point HFMSE increase (P<0.001). • Adverse-event incidence similar between groups (93% vs 100%).
Intervention
Intrathecal nusinersen 12 mg on days 1, 29, 85, and 274 vs. sham procedure (needle prick to lower back covered with bandage)
Inclusion Criteria
Genetically confirmed 5q SMA with symptom onset after 6 months of age (likely SMA type 2 or 3); age 2–12 years; able to sit independently but never able to walk independently (defined as walking ≥15 ft unaided); HFMSE score 10–54; no severe contractures, severe scoliosis (Cobb >40°), respiratory insufficiency, or gastric tube.
Study Design
Arms: Nusinersen (n=84), Sham control (n=42)
Outcome
Significant improvement in motor function with nusinersen: LS mean HFMSE change +3.9 vs −1.0 (difference 4.9 points, 95% CI 3.1–6.7) at month 15; 57% vs 26% achieved ≥3-point HFMSE improvement (P<0.001). Trial halted early after prespecified interim analysis (difference 5.9 points, 95% CI 3.7–8.1; P<0.001).