TABLE 2.
Global tests of fixed effects, means and contrasts for FVC, FEV1, ALSFRS‐R at different visit times in each treatment arm (ITT population)
| FVC | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Tests of fixed effects | |||||||||
| Effect | Week | Treatment | Week*treatment | ||||||
| p value | <0.0001 | 0.9928 | 0.0101 | ||||||
| Effect | Follow‐up | Follow‐up*treatment | |||||||
| p value | 0.1387 | 0.1734 | |||||||
| Estimated means and contrasts | |||||||||
| Visit time (week) | RNS60 | Placebo | Difference (RNS60 – placebo) | ||||||
| Mean | SE | p | Mean | SE | p | Mean | SE | p | |
| Treatment period | |||||||||
| 0 | 102.6 | 1.9 | <0.0001 | 102.6 | 2.0 | <0.0001 | ‐0.02 | 2.8 | 0.9928 |
| 4 | 100.7 | 2.1 | <0.0001 | 99.1 | 2.1 | <0.0001 | 1.6 | 2.9 | 0.5778 |
| 12 | 97.0 | 2.5 | <0.0001 | 92.1 | 2.5 | <0.0001 | 4.9 | 3.5 | 0.1647 |
| 24 | 91.4 | 3.5 | <0.0001 | 81.6 | 3.5 | <0.0001 | 9.8 | 4.9 | 0.0474 |
| Slope (treatment period) | −0.46 | 0.11 | <0.0001 | −0.87 | 0.1 | <0.0001 | 0.41 | 0.16 | 0.0101 |
| Follow‐up period (off‐treatment) | |||||||||
| 36 | 86.0 | 3.7 | <0.0001 | 75.1 | 3.8 | <0.0001 | 10.9 | 5.3 | 0.0394 |
| 48 | 80.6 | 4.4 | <0.0001 | 68.6 | 4.6 | <0.0001 | 12.0 | 6.3 | 0.0571 |
| Slope (follow‐up period) | −0.45 | 0.11 | <0.0001 | −0.54 | 0.13 | <0.0001 | 0.09 | 0.18 | 0.5924 |
| FEV1 | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Tests of fixed effects | |||||||||
| Effect | Week | Treatment | Week*treatment | ||||||
| p value | <0.0001 | 0.8723 | 0.0146 | ||||||
| Effect | Follow‐up | Follow‐up*treatment | |||||||
| p value | 0.4219 | 0.1148 | |||||||
| Estimated means and contrasts | |||||||||
| Visit time (week) | RNS60 | Placebo | Difference (RNS60 – placebo) | ||||||
| Mean | SE | p | Mean | SE | p | Mean | SE | p | |
| Treatment period | |||||||||
| 0 | 96.7 | 2.2 | <0.0001 | 97.2 | 2.2 | <0.0001 | −0.5 | 3.1 | 0.8723 |
| 4 | 95.2 | 2.2 | <0.0001 | 94.1 | 2.2 | <0.0001 | 1.1 | 3.1 | 0.7107 |
| 12 | 92.3 | 2.5 | <0.0001 | 87.9 | 2.5 | <0.0001 | 4.4 | 3.5 | 0.2128 |
| 24 | 87.9 | 3.4 | <0.0001 | 78.6 | 3.5 | <0.0001 | 9.3 | 4.9 | 0.0563 |
| Slope (treatment period) | −0.36 | 0.1 | 0.0022 | −0.77 | 0.1 | <0.0001 | 0.41 | 0.2 | 0.0146 |
| Follow‐up period (off‐treatment) | |||||||||
| 36 | 82.6 | 3.7 | <0.0001 | 72.3 | 3.8 | <0.0001 | 10.3 | 5.3 | 0.0522 |
| 48 | 77.2 | 4.3 | <0.0001 | 66.0 | 4.4 | <0.0001 | 11.2 | 6.1 | 0.0678 |
| Slope (follow‐up period) | −0.45 | 0.1 | <0.0001 | −0.52 | 0.1 | <0.0001 | 0.07 | 0.1 | 0.5758 |
| ALSFRS‐R | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Tests of fixed effects | |||||||||
| Effect | Week | Treatment | Week*treatment | ||||||
| p value | <0.0001 | 0.9076 | 0.5725 | ||||||
| Effect | Follow‐up | Treatment*follow‐up | |||||||
| p value | 0.3181 | 0.3363 | |||||||
| Estimated means and contrasts | |||||||||
| Week | RNS60 | Placebo | Difference (RNS60 – placebo) | ||||||
| Mean | SE | p | Mean | SE | p | Mean | SE | p | |
| Treatment period | |||||||||
| 0 | 41.4 | 0.4 | <0.0001 | 41.3 | 0.4 | <0.0001 | 0.1 | 0.6 | 0.9076 |
| 4 | 40.4 | 0.5 | <0.0001 | 40.2 | 0.5 | <0.0001 | 0.2 | 0.7 | 0.8010 |
| 12 | 38.3 | 0.6 | <0.0001 | 37.9 | 0.6 | <0.0001 | 0.4 | 0.9 | 0.6877 |
| 24 | 35.1 | 0.9 | <0.0001 | 34.5 | 1.0 | <0.0001 | 0.6 | 1.3 | 0.6280 |
| Slope (treatment period) | −0.26 | 0.03 | <0.0001 | –0.28 | 0.03 | <0.0001 | 0.02 | 0.04 | 0.5725 |
| Follow‐up period (off‐treatment) | |||||||||
| 36 | 32.0 | 1.1 | <0.0001 | 31.6 | 1.1 | <0.0001 | 0.4 | 0.6 | 0.8048 |
| 48 | 28.9 | 1.3 | <0.0001 | 28.8 | 1.3 | <0.0001 | 0.1 | 1.9 | 0.9493 |
| Slope (follow‐up period) | −0.26 | 0.03 | <0.0001 | –0.24 | 0.03 | <0.0001 | –0.02 | 0.04 | 0.5728 |
| ALSAQ‐40 (Eating and drinking) | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Tests of fixed effects | |||||||||
| Effect | Week | Treatment | Week*treatment | ||||||
| p value | <0.0001 | 0.5022 | 0.0319 | ||||||
| Estimated means and contrasts | |||||||||
| Week | RNS60 | Placebo | Difference (RNS60 – placebo) | ||||||
| Mean | SE | p | Mean | SE | p | Mean | SE | p | |
| 0 | 15.9 | 2.8 | <0.0001 | 13.3 | 2.8 | <0.0001 | 2.6 | 3.9 | 0.5022 |
| 24 (end of treatment) | 20.4 | 3.2 | <0.0001 | 22.4 | 3.2 | <0.0001 | −2.0 | 4.5 | 0.6524 |
| 48 (follow‐up) | 24.9 | 4.1 | <0.0001 | 31.6 | 4.2 | <0.0001 | −6.7 | 5.8 | 0.2521 |
| Slope | 0.19 | 0.1 | 0.0032 | 0.38 | 0.1 | <0.0001 | −0.19 | 0.1 | 0.0319 |
Abbreviations: ALSAQ‐40, Amyotrophic Lateral Sclerosis Assessment Questionnaire‐40; ALSFRS‐R, Amyotrophic Lateral Sclerosis Functional Rating Scale—Revised; BMI, body mass index; FEV, forced expiratory volume; FVC, forced vital capacity; ITT, intention to treat.