A Phase II Study Comparing Low- and High-Dose Alemtuzumab and High-Dose Rebif® in Patients With Early, Active Relapsing-Remitting Multiple Sclerosis
|Multiple Sclerosis, Relapsing-Remitting||Biological: Interferon beta-1a Biological: Alemtuzumab 12 mg Biological: Alemtuzumab 24 mg||Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||A Phase II, Randomized, Open-Label, Three-Arm Study Comparing Low- and High-Dose Alemtuzumab and High-Dose Subcutaneous Interferon Beta-1a (Rebif®) in Patients With Early, Active Relapsing-Remitting Multiple Sclerosis|
- Probability of Participants With Sustained Accumulation of Disability (SAD) [ Time Frame: Up to 3 years ]EDSS is an ordinal scale in half-point increments that quantifies disability in participants with MS. It assesses 7 functional systems (visual, brainstem, pyramidal, cerebellar, sensory, bowel/bladder and cerebral) as well as ambulation. EDSS total score: 0 (normal neurological examination) to 10 (death due to MS). As measured by EDSS score, SAD was defined as increase of at least 1.5 points for participants with Baseline score of 0 and increase of at least 1.0 point for participants with Baseline score of 1.0 or more; and the increase persisted for at least next the 2 scheduled assessments, that is, 6 consecutive months. The onset date of SAD was date of first EDSS assessment that began 6 month consecutive period of SAD. Participants who did not reach SAD endpoint were censored at their last visit. Probability of participants with SAD, estimated by Kaplan-Meier (KM) method, was reported.
- Annualized Relapse Rate [ Time Frame: Up to 3 years ]Relapse was defined as new neurological symptoms or worsening of previous neurological symptoms with an objective change on neurological examination, attributable to multiple sclerosis that lasted for at least 48 hours, that were present at normal body temperature, and that were preceded by at least 30 days of clinical stability. Annualized relapse rate was estimated using a Poisson regression model with observed number of relapses as a dependent variable, the log total amount of follow-up from date of randomization for each participant as an offset variable and treatment group indicator as a covariate.
- Probability of Participants Who Were Relapse Free at 3 Years After Initial Treatment [ Time Frame: Year 3 ]Participants were considered relapse free at Year 3 if they did not experience a relapse between randomization and study completion at 36 months. Participants who discontinued early were considered relapse free if they did not experience a relapse prior to discontinuation. Probability of participants who were relapse free at Year 3, estimated using the KM method, was reported.
- Percent Change From Baseline in T1 Cerebral Volume at Year 3 [ Time Frame: Baseline, Year 3 ]Magnetic resonance imaging (MRI) T1 was used to determine rate of cerebral atrophy (decrease in cerebral/brain volume). Partial brain volumes were measured using the technique of Losseff et al. (1996). Percent change in cerebral volume at Year 3 was calculated from MRI-T1-weighted scans as: 100*([brain volume at Year 3] minus [brain volume at Baseline]) divided by [brain volume at Baseline]).
- Percent Change From Baseline in MRI T2 Lesion Volume at Year 3 [ Time Frame: Baseline, Year 3 ]Percent change in lesion volume at Year 3 was calculated from MRI-T2-weighted scans as: 100*([lesion volume at Year 3] minus [lesion volume at Baseline]) divided by [lesion volume at Baseline]).
|Study Start Date:||December 2002|
|Study Completion Date:||January 2010|
|Primary Completion Date:||September 2007 (Final data collection date for primary outcome measure)|
|Active Comparator: Interferon Beta-1a||
Biological: Interferon beta-1a
Interferon beta-1a 44 microgram (mcg) subcutaneously 3-times weekly for 36 months.
Other Name: Rebif®
|Experimental: Alemtuzumab 12 mg||
Biological: Alemtuzumab 12 mg
Alemtuzumab 12 milligram per day (mg/day) was given by intravenous infusion on 5 consecutive days during the first month and on 3 consecutive days at months 12 and 24 (the latter at the treating physicians' discretion if the cluster of differentiation 4+ [CD4+] T-cell count was >=100*10^6 cells per liter).
Other Name: Lemtrada
|Experimental: Alemtuzumab 24 mg||
Biological: Alemtuzumab 24 mg
Alemtuzumab 24 mg/day was given by intravenous infusion on 5 consecutive days during the first month and on 3 consecutive days at months 12 and 24 (the latter at the treating physicians' discretion if the CD4+ T-cell count was >=100*10^6 cells per liter).
Other Name: Lemtrada
The aims of MS therapy are to prevent the progression of disease and accumulation of long-term disability. The hypothesis underlying this study was that aggressive treatment of inflammation in the brain early in the course of MS would protect the participant from disease progression and accumulating disability.
This protocol compared two different doses of alemtuzumab and high-dose, high frequency of SC interferon beta-1a to evaluate the safety profiles of the respective treatments and to evaluate efficacy in terms of:
- Slowing the sustained accumulation of disability in participant with MS;
- Reducing the frequency of relapses experienced by participant with MS; and
- Reducing the harmful effects of MS on the brain, as assessed by magnetic resonance imaging (MRI)
Participants who received alemtuzumab during the initial 36-month treatment period may have been eligible for re-treatment with alemtuzumab in the extension study CAMMS03409 (NCT00930553) to evaluate:
- How long the effects of prior alemtuzumab treatment lasted;
- If additional treatments with alemtuzumab continued to reduce the effects of MS; and
- What kind of side effects participants experienced upon retreatment with alemtuzumab
Please refer to this study by its ClinicalTrials.gov identifier: NCT00050778
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|Study Director:||Medical Monitor||Genzyme, a Sanofi Company|