drug and clinical outcome, although the diagnosis of relapse and the decision to treat relapses with steroids were made by unblinded treating physicians. A multivariate analysis of five clinical variables (EDSS, Ambulation Index [AI], number of relapses requiring treatment with steroids, months to first relapse needing treatment with steroids, and Standard Neurological Status [SNS]) was used to determine primary efficacy. The AI is an ordinal scale ranging from 0 to 9 in one point increments to define progressive ambulatory impairment. The SNS provides an overall measure of neurologic impairment and disability, with scores ranging from 0 (normal neurologic examination) to 99 (worst possible score).
Results of Study 1 are summarized in Table 1.
|
Treatment Groups |
p-value |
|
|
|
NOVANTRONE |
Placebo vs
12 mg/m2
NOVANTRONE |
|
Primary Endpoints |
Placebo
(N = 64) |
5 mg/m2
(N = 64) |
12 mg/m2
(N = 60) |
|
NR = not reached within 24 months; MRI = magnetic resonance imaging. |
|
* Wei-Lachin test. |
|
** Month 24 value minus baseline. |
|
‡ A subset of 110 patients was selected for MRI analysis. MRI results were not available for all patients at all time points. |
|
Primary efficacy multivariate analysis* |
- |
- |
- |
< 0.0001 |
|
Primary clinical variables analyzed: |
|
|
|
|
|
EDSS change** (mean) |
0.23 |
– 0.23 |
– 0.13 |
0.0194 |
|
Ambulation Index change** (mean) |
0.77 |
0.41 |
0.30 |
0.0306 |
Mean number of relapses per patient requiring
corticosteroid treatment (adjusted for discontinuation) |
1.20 |
0.73 |
0.40 |
0.0002 |
Months to first relapse requiring corticosteroid treatment
(median [1st quartile]) |
14.2 [6.7] |
NR [6.9] |
NR [20.4] |
0.0004 |
|
Standard Neurological Status change** (mean) |
0.77 |
– 0.38 |
– 1.07 |
0.0269 |
|
MRI‡ |
|
|
|
|
|
No. of patients with new Gd-enhancing lesions |
5/32 (16%) |
4/37 (11%) |
0/31 |
0.022 |
|
Change in number of T2-weighted lesions, mean (n)** |
1.94 (32) |
0.68 (34) |
0.29 (28) |
0.027 |
A subset of 110 patients was selected for MRI analysis. MRI results were not available for all patients at all time points.
A second randomized, controlled study (Study 2) eva luated NOVANTRONE in combination with methylprednisolone (MP) and was conducted in patients with secondary progressive or worsening relapsing-remitting multiple sclerosis who had residual neurological deficit between relapses. All p
|
