Table 1 Parts B and C: baseline demographics and disease characteristics

From: High-dose nusinersen for spinal muscular atrophy: a phase 3 randomized trial

Part B: cohort with infantile-onset SMA

50/28 mg (n = 50)

12/12 mg (n = 25)

Matched sham (ENDEAR)a (n = 20)

Age at first dose, weeks

Mean (s.d.) (range)

Median (Q1, Q3)

18.4 (9.15) (2 to 33)

18.4 (10.9 to 26.0)

16.5 (8.03) (3 to 31)

15.9 (11.9 to 21.0)

22.0 (7.96) (4 to 34)

22.2 (16.6 to 29.2)

Age at symptom onset, weeks

Mean (s.d.) (range)

Median (Q1, Q3)

7.5 (5.26) (1 to 21)

6.0 (3.0 to 12.0)

5.8 (4.44) (2 to 20)

4.0 (3.0 to 8.0)

8.8 (5.11) (1 to 19)

8.0 (5.5 to 13.0)

Disease duration at informed consent, weeks, mean (s.d.) (range)

9.6 (5.29) (0 to 20)

9.1 (6.11) (0 to 25)

11.1 (4.92) (0 to 21)

CHOP-INTEND total score, mean (s.d.) (range)

20.9 (10.23) (5 to 56)

19.9 (9.63) (0 to 39)

23.6 (5.84) (11 to 33)

HINE-2 score, mean (s.d.) (range)

1.4 (1.36) (0 to 5)

1.4 (1.29) (0 to 4)

1.3 (1.02) (0 to 4)

Plasma NfL, pg ml−1

n

Mean (s.d.) (range), pg ml−1

Geometric mean (95% CI)

40

304.7 (283.9) (78.6 to 1,480.0)

253.3 (190.2 to 291.0)

22

329.4 (175.9) (83.9 to 678.0)

287.6 (225.9 to 366.2)

20

287.3 (140.4) (119.0 to 691.0)

260.3 (211.2 to 320.9)

Geography, n (%)

Asia-Pacific

Europe

North America

South/Central America

20 (40)

12 (24)

1 (2)

17 (34)

8 (32)

7 (28)

0

10 (40)

2 (10)

5 (25)

13 (65)

0

Part B: cohort with later-onset SMA

50/28 mg (n = 16)

12/12 mg (n = 8)

Matched sham (CHERISH)b (n = 16)

Matched 12/12 mg (CHERISH)b (n = 32)

Age at first dose, years

Mean (s.d.) (range)

Median (Q1, Q3)

6.1 (2.59) (2.1 to 9.8)

6.1 (4.2 to 8.2)

5.7 (3.00) (2.0 to 9.3)

5.7 (2.8 to 8.5)

5.1 (1.82) (2.1 to 7.5)

5.1 (3.9 to 6.8)

5.5 (1.83) (2.1 to 9.2)

5.4 (4.5 to 6.7)

Age at symptom onset, months

Mean (s.d.) (range)

Median (Q1, Q3)

11.1 (4.11) (6.0 to 22.0)

11.5 (8.5 to 12.0)

9.9 (2.36) (7.0 to 15.0)

9.0 (9.0 to 10.5)

11.9 (3.85) (7.0 to 20.0)

10.5 (9.0 to 15.0)

10.7 (3.49) (6.0 to 18.0)

10.0 (7.5 to 13.0)

SMN2 copy number, n (%)

2

3

≥4

0

15 (94)

1 (6)

1 (13)

7 (88)

0

3 (18.8)

12 (75.0)

1 (6.3)

3 (9.4)

28 (87.5)

1 (3.1)

HFMSE score

Mean (s.d.) (range)

20.3 (10.05) (10.0 to 42.0)

13.8 (4.59) (10.0 to 22.0)

21.4 (7.49) (13.0 to 34.0)

21.8 (8.60) (10.0 to 43.0)

RULM score

Mean (s.d.) (range)

20.2 (5.31) (12.0 to 30.0)

14.9 (5.96) (4.0 to 25.0)

20.9 (4.99) (12.0 to 28.0)

20.6 (6.04) (11.0 to 33.0)

WHO motor milestone

Mean (s.d.) (range)

1.6 (1.09) (1.0 to 5.0)

1.0 (0) (1.0 to 1.0)

1.4 (0.62) (1.0 to 3.0)

1.4 (1.01) (1.0 to 5.0)

Plasma NfL, pg ml−1

Mean (s.d.) (range)

Geometric mean (95% CI)

15.0 (14.45) (3.1 to 58.6)

10.9 (7.12 to 16.59)

9.7 (3.32) (6.1 to 16.9)

9.3 (7.14 to 11.98)

14.0 (10.1) (5.3 to 46.4)

11.8 (8.62 to 16.22)

13.2 (9.6) (3.5 to 47.4)

10.6 (8.16 to 13.79)

Part C

Infantile-onset SMA

Later-onset SMA

Total

(n = 2)

Aged <18 years (n = 14)

Aged ≥18 years

(n = 24)

n = 40

Age at first study dose, years, median (range)

4.8 (4 to 6)

10.3 (5 to 17)

32.5 (19 to 65)

23.0 (4 to 65)

Time on 12/12 mg nusinersen, years, median (range)

3.2 (3 to 4)

3.9 (2 to 4)

3.9 (1 to 5)

3.9 (1 to 5)

Sex, female, n (%)

 

1 (50)

6 (42.9)

8 (33.3)

15 (37.5)

Age at symptom onset, months, median (range)

5 (4 to 6)

11.5 (6 to 72)

36.0 (12 to 192)

24.0 (4 to 192)

SMN2 copy number, n (%)

1

2

3

4

Other: 2–3 or 3–4

0

0

2 (100)

0

0

0

1 (7)

12 (86)

1 (7)

0

1 (4)

2 (8)

6 (25)

13 (54)

2 (8)

1 (3)

3 (8)

20 (50)

14 (35)

2 (5)

Achieved and maintained milestone, n (%)

Sat without support

Stood without support

Walked with support

Walked (at least 4.6 meters) independently

1 (50)

0

0

0

12 (86)

3 (21)

5 (36)

3 (21)

24 (100)

19 (79)

18 (75)

18 (75)

37 (93)

22 (55)

23 (58)

21 (53)

HFMSE score

n

Mean (s.d.) (range)

2

17.5 (17.7) (5 to 30)

13

28.2 (16.7) (0 to 49)

23

40.6 (16.35) (7 to 64)

38

35.1 (17.61) (0 to 64)

RULM score

n

Mean (s.d.) (range)

2

15 (0) (15)

12

23.2 (9.67) (0 to 34)

24

32.2 (6.63) (17 to 37)

38

28.4 (9.12) (0 to 37)

Plasma NfL, pg ml−1

Mean (s.d.) (range)

Geometric mean (95% CI)

6.8 (1.6) (5.7 to 8.0)

6.7 (0.76 to 59.55)

5.0 (2.4) (0.7 to 9.5)

4.2 (2.75 to 6.46)

6.5 (3.3) (1.9 to 14.4)

5.8 (4.67 to 7.12)

6.0 (3.0) (0.7 to 14.4)

5.2 (4.34 to 6.32)

  1. aPrespecified matched sham group from ENDEAR based on disease duration and baseline CHOP-INTEND score.
  2. bPrespecified propensity-score matching was used to select sham control and 12/12 mg (three loading doses over 85 days with maintenance doses every 6 months thereafter) participants from CHERISH who were comparable at baseline to the 50/28 mg group from DEVOTE on key prognostic factors: age, HFMSE and RULM at baseline. Despite matching, a residual imbalance in age remained between the matched sham group and the 50/28 mg group. Q, quarter.
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