Table 3.
Secondary endpoints (according to the protocol pre-defined rank).
| Endpoint | Double-blind, placebo-controlled phase | Extension phase | ||||
|---|---|---|---|---|---|---|
| MD1003 (n = 103) | Placebo (n = 51) | p value | MD1003 > MD1003 (n = 91) | Placebo > MD1003 (n = 42) | p value | |
| Change in EDSS,a mean (SD) | −0.03 (0.50) | 0.13 (0.33) | 0.01 | 0.04 (0.62) | 0.15 (0.37) | 0.13 |
| Change in MSWS,a mean (SD) (seconds) | 0.79 (17.12) | 5.26 (22.51) | 0.81 | 2.06 (17.22) | 5.05 (27.07) | 0.64 |
| CGI,b mean (SD) | 4.05 (0.81) | 4.62 (0.75) | <0.001 | 4.17 (0.97) | 4.21 (0.75) | 0.93 |
| SGI,b mean (SD) | 4.27 (1.05) | 4.76 (0.89) | 0.009 | 4.47 (1.07) | 4.41 (0.87) | 0.72 |
| Change in TW25,a mean (SD) (%) | 67.71 (203.27) | 98.18 (253.73) | 0.64 | 95.77 (221.66) | 121.51 (256.29) | 0.82 |
| Patients with improvement of EDSS and TW25,c,d n (%) | 2 (1.9) | 0 (0.0) | 0.99 | 2 (2.2) | 0 (0.0) | 0.99 |
| Patients with improvement of EDSS,c,e n (%) | 10 (9.7) | 0 (0.0) | 0.03 | 10 (11.0) | 2 (4.8) | 0.34 |
| Patients with EDSS progression,c,f n (%) | 4 (4.2) | 6 (13.6) | 0.07 | 8 (9.9) | 13 (31.7) | 0.005 |
| Patients with stable EDSS score,c n (%) | 81 (78.6) | 38 (74.5) | 0.68 | 63 (69.2) | 26 (61.9) | 0.43 |
| Change in SF-36 score,a mean (SD) | ||||||
| General health | −4.43 (16.75) | 2.25 (16.23) | 0.03 | −3.95 (15.68) | 1.37 (19.26) | 0.17 |
| Health change | 3.54 (24.49) | 3.65 (29.17) | 0.90 | 1.44 (24.81) | 14.10 (24.19) | 0.01 |
| Physical functioning | −1.72 (26.70) | 0.50 (22.14) | 0.73 | −3.53 (26.45) | −1.36 (23.58) | 0.92 |
| Social functioning | −0.24 (28.38) | −0.25 (26.52) | 0.97 | 0.82 (25.60) | 2.08 (28.55) | 0.99 |
| Role limitations due to physical health | 8.58 (46.29) | 1.17 (33.71) | 0.26 | 2.01 (44.35) | 6.35 (33.43) | 0.36 |
| Role limitations due to emotional problems | 2.43 (43.00) | −0.67 (45.42) | 0.88 | 0.18 (46.11) | 7.14 (45.70) | 0.48 |
| Pain | 0.12 (18.93) | −2.55 (19.79) | 0.46 | −1.89 (20.73) | −1.61 (16.81) | 0.86 |
| Energy or fatigue | −2.85 (19.01) | 0.82 (14.87) | 0.25 | 1.35 (16.91) | 6.71 (17.21) | 0.07 |
| Emotional well-being | −4.41 (17.15) | 1.33 (13.78) | 0.05 | −1.31 (17.70) | −0.38 (13.88) | 0.83 |
| Change in MFIS,a mean (SD) | 1.38 (16.04) | 1.30 (15.69) | 0.85 | −0.40 (13.49) | 0.79 (13.88) | 0.97 |
| Change in 9-HPT,a mean (SD) (seconds) | ||||||
| Best hand | 2.06 (5.21) | 1.40 (7.06) | 0.98 | 3.43 (8.44) | 2.76 (9.20) | 0.77 |
| Worst hand | 3.14 (25.03) | 1.49 (14.98) | 0.67 | 8.87 (33.86) | 7.70 (32.17) | 0.77 |
| Change in EDSS subscores,a mean (SD) | ||||||
| Visual | 0.05 (0.81) | −0.10 (0.50) | 0.18 | 0.04 (1.00) | 0.17 (1.19) | 0.73 |
| Brain stem | 0.10 (0.69) | −0.08 (0.82) | 0.19 | 0.09 (0.89) | 0.14 (0.84) | 0.58 |
| Pyramidal | −0.03 (0.55) | 0.04 (0.53) | 0.54 | 0.12 (0.61) | 0.12 (0.59) | 0.88 |
| Cerebellar | 0.19 (0.86) | 0.14 (1.12) | 0.54 | 0.09 (0.91) | 0.05 (1.53) | 0.82 |
| Sensory | −0.25 (0.93) | 0.06 (0.88) | 0.09 | −0.08 (0.96) | −0.17 (0.99) | 0.64 |
| Bowel and bladder | 0.14 (0.83) | 0.20 (0.98) | 0.68 | 0.12 (0.89) | 0.02 (0.92) | 0.81 |
| Cerebral | −0.08 (0.76) | 0.08 (0.91) | 0.26 | −0.01 (0.89) | 0.00 (0.96) | 0.75 |
9-HPT: nine-hole peg test; CGI: clinician-assessed Clinical Global Impression Scale; EDSS: Expanded Disability Status Scale; MFIS: modified Fatigue Impact Scale; MSWS: Multiple Sclerosis Walking Scale; SD: standard deviation; SF-36: Short Form 36 Health Survey; SGI: subject-assessed Clinical Global Impression Scale; TW25: timed 25-foot walk.
Mean values and percentages are calculated for the number of patients evaluated at the specified treatment visit. p values indicate comparison between the MD1003 and placebo arms.
From month 0 to month 12 during the placebo-controlled phase and from month 0 to month 24 during the extension phase.
Assessed at month 12 during the placebo-controlled phase and month 24 during the extension phase.
At month 9, confirmed at month 12, during the placebo-controlled phase and at month 18, confirmed at month 24, during the extension phase.
Clinical improvement was defined as a decrease of ⩾0.5 point or ⩾1 point for EDSS (if baseline score was 6–7 or 4.5–5.5, respectively) or a decrease of ⩾20% for TW25 time.
Same criteria from improvement in EDSS as for the primary endpoint.
⩾0.5 point or ⩾1 point if value at randomisation was 4.5–5.5.