3. Intrathecally‐injected nusinersen versus sham procedure (Finkel 2017 (ENDEAR)).
| Nusinersen | Sham procedure | Risk ratio (95% CI) | Hazard ratio (95% CI) | P value | |
| Number of participants randomised and included in time‐to‐event analysis | 80 (100%) | 41 (100%) | |||
| Number (%) of participants who died or had received permanent (> 16 hours per day) ventilation | 21 (39%) | 28 (68%) | ‐ | 0.53 (0.32 to 0.89) | 0.005 |
| Number (%) of participants evaluable for interim analysisa | 51 (63%) | 27 (66%) | |||
| Number (%) of participants achieving motor milestone response on HINE‐2 (interim analysis)bc | 21 (41%) | 0 (0%) | 23.15 (1.46 to 368.01) | ‐ | 0.03 |
| Number (%) of participants evaluable in final analysisb | 73 (91%) | 37 (90%) | |||
| Number (%) of participants who survived until the end of trialb | 67 (91%) | 25 (68%) | ‐ | 0.37 (0.18 to 0.77) | 0.004 |
| Number (%) of participants who did not use permanent (> 16 hours per day) assisted ventilation until the end of trialb | 62 (85%) | 28 (76%) | ‐ | 0.66 (0.3 to 1.37) | 0.13 |
| Number (%) of participants achieving motor milestone response on HINE‐2 (final analysis)bc | 37 (51%) | 0 (0%) | 38.51 (2.43 to 610.14) | ‐ | 0.010 |
| Number (%) of participants achieving head controlb | 16 (22%) | 0 (0%) | 16.95 (1.04 to 274.84) | ‐ | 0.05 |
| Number (%) of participants able to roll overb | 7 (10%) | 0 (0%) | 7.7 (0.45 to 131.29) | ‐ | 0.16 |
| Number (%) of participants able to sit independentlyb | 6 (8%) | 0 (0%) | 6.68 (0.39 to 115.38) | ‐ | 0.19 |
| Number (%) of participants able to standb | 1 (1%) | 0 (0%) | 1.54 (0.06 to 36.92) | ‐ | 0.79 |
| Number (%) of participants with response on the CHOP INTENDbd | 52 (71%) | 1 (3%) | 26.36 (3.79 to 183.18) | ‐ | <0.001 |
| Nusinersen | Sham procedure | Risk ratio (95% CI) | P value | ||
| Number (%) of adverse eventse | 77 (96%) | 40 (98%) | 0.99 (0.92 to 1.05) | ‐ | 0.68 |
| Number (%) of participants with adverse events occurring < 72 hours of treatment or sham procedure | 51 (64%) | 24 (59%) | 1.08 (0.81 to 1.43) | ‐ | 0.58 |
| Number (%) of participants with severe adverse events | 45 (56%) | 33 (80%) | 0.70 (0.55 to 0.89) | ‐ | 0.004 |
aInterim analysis included all participants that had a day 183 visit at the time of cut‐off (15 June 2016). bFinal analysis was performed on data, including participants fulfilling at least six months of trial enrolment. cResponse was defined according to scores on the HINE‐2, which assesses the development of motor function through the achievement of motor milestones; in this trial, the scores accounted for seven of the eight motor milestone categories, excluding voluntary grasp. Infants were considered to have a motor milestone response if they met the following two criteria: improvement in at least one category (i.e. an increase in the score for head control, rolling, sitting, crawling, standing, or walking of ≥ 1 point, an increase in the score for kicking of ≥ 2 points, or achievement of the maximal score for kicking) and more categories with improvement than categories with worsening (i.e. a decrease was defined as ≥ 1 point decrease in the score for head control, rolling, sitting, crawling, standing, or walking and a decrease in the score for kicking was defined as a decrease of ≥ 2 points). d Response was defined as an increase of at least 4 points from baseline in the CHOP INTEND score at the end of trial visit (day 183, 302, or 394). e In case a participant had more than one event, only the event with the highest severity was counted.
HINE: Hammersmith Infant Neurological Examination; CHOP INTEND: Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders