Follow up of MBP8298

A board to discuss future MS therapies in early stage (Phase I or II) trials.

Follow up of MBP8298

Postby scoobyjude » Sat Aug 12, 2006 6:47 pm

Intravenous synthetic peptide MBP8298 delayed disease progression in an HLA Class II-defined cohort of patients with progressive multiple sclerosis: results of a 24-month double-blind placebo-controlled clinical trial and 5 years of follow-up treatment.

Warren KG, Catz I, Ferenczi LZ, Krantz MJ.

Multiple Sclerosis Patient Care and Research Clinic, Division of Neurology, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.

MBP8298 is a synthetic peptide with a sequence corresponding to amino acid residues 82-98 of human myelin basic protein (DENPVVHFFKNIVTPRT). It represents the immunodominant target for both B cells and T cells in multiple sclerosis (MS) patients with HLA haplotype DR2. Its administration in accordance with the principle of high dose tolerance results in long-term suppression of anti-myelin basic protein (MBP) autoantibody levels in the cerebrospinal fluid (CSF) of a large fraction of progressive MS patients. MBP8298 was evaluated in a 24-month placebo-controlled double-blinded Phase II clinical trial in 32 patients with progressive MS. The objective was to assess the clinical efficacy of 500 mg of MBP8298 administered intravenously every 6 months, as measured by changes in Expanded Disability Status Scale (EDSS) scores. Contingency analysis for all patients at 24 months showed no significant difference between MBP8298 and placebo-treatments (n = 32, P = 0.29). Contingency analysis in an HLA Class II defined subgroup showed a statistically significant benefit of MBP8298 treatment compared with placebo in patients with HLA haplotypes DR2 and/or DR4 (n = 20, P = 0.01). Long-term follow-up treatment and assessment of patients in this responder group showed a median time to progression of 78 months for MBP8298 treated patients compared with 18 months for placebo-treatment (Kaplan-Meier analysis, P = 0.004; relative rate of progression = 0.23). Anti-MBP autoantibody levels in the CSF of most MBP8298 treated patients were suppressed, but antibody suppression was not predictive of clinical benefit. Anti-MBP autoantibodies that reappeared in the CSF of one patient at 36 months, whilst under treatment with MBP8298, were not reactive with the MBP8298 peptide in vitro. The identification of a responder subgroup (62.5% of the patients in this study) enables a more efficient design of a large confirmatory clinical trial of MBP8298. The probability that patients with other less common HLA-DR haplotypes will respond to this treatment should not be ignored.
User avatar
scoobyjude
Family Elder
 
Posts: 516
Joined: Sat Feb 18, 2006 4:00 pm
Location: suburb of Chicago, IL USA

Advertisement

Return to Drug Pipeline

 


  • Related topics
    Replies
    Views
    Last post
  • MBP8298
    by dignan » Wed May 03, 2006 7:52 am
    5 Replies
    2658 Views
    Last post by dignan View the latest post
    Thu Jun 22, 2006 8:24 am
  • MBP8298
    by bromley » Thu Sep 07, 2006 9:48 am
    1 Replies
    1208 Views
    Last post by gwa View the latest post
    Thu Sep 07, 2006 10:51 am
  • MBP8298
    by bromley » Thu Oct 12, 2006 11:39 am
    0 Replies
    1049 Views
    Last post by bromley View the latest post
    Thu Oct 12, 2006 11:39 am
  • MBP8298
    by dignan » Thu Apr 05, 2007 1:30 pm
    0 Replies
    1164 Views
    Last post by dignan View the latest post
    Thu Apr 05, 2007 1:30 pm
  • MBP8298
    by dignan » Tue Jun 05, 2007 2:20 pm
    0 Replies
    1348 Views
    Last post by dignan View the latest post
    Tue Jun 05, 2007 2:20 pm

Who is online

Users browsing this forum: No registered users


Contact us | Terms of Service