ssessed with magnetic resonance imaging (MRI) at baseline, Month 12, and Month 24. Neurologic assessments and MRI reviews were performed by eva luators blinded to study 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.
Table 1 Efficacy Results at Month 24 Study 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
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 second randomized, controlled study (Study 2) eva luated
