RE DIRUCOTIDE CLINICAL TRIAL FOR SPMS PATINTS

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RE DIRUCOTIDE CLINICAL TRIAL FOR SPMS PATINTS

Postby seeva » Sat Jan 25, 2014 4:12 am

DEAR Friends please read the following about the new drug to be trial specifically designed for spms patients
http://myjourneywithms-kimberly.blogspo ... ntial.html
regards
seeva
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Re: RE DIRUCOTIDE CLINICAL TRIAL FOR SPMS PATINTS

Postby NHE » Sat Jan 25, 2014 8:50 am

seeva wrote:DEAR Friends please read the following about the new drug to be trial specifically designed for spms patients
http://myjourneywithms-kimberly.blogspo ... ntial.html
regards
seeva


That looks like old information. It's from 2009. Both the MAESTRO-02 and MAESTRO-03 trials were terminated due to negative results in the MAESTRO-01 trial.

http://www.clinicaltrials.gov/ct2/resul ... rch=Search

Also see...

Dirucotide Does Not Meet Primary Endpoint in Phase III MAESTRO-01 Trial in Secondary Progressive Multiple Sclerosis
http://news.bio-medicine.org/?q=medicin ... rosis-4785
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Re: RE DIRUCOTIDE CLINICAL TRIAL FOR SPMS PATINTS

Postby NHE » Sat Jan 25, 2014 9:24 am

The results of MAESTRO-01 were published in 2011.

A phase III study evaluating the efficacy and safety of MBP8298 in secondary progressive MS.
Neurology. 2011 Oct 18;77(16):1551-60

    OBJECTIVE:
    To evaluate the efficacy and safety of MBP8298 in subjects with secondary progressive multiple sclerosis (SPMS) who express human leukocyte antigen (HLA) haplotype DR2 or DR4 (DR2(+) or DR4(+)).

    METHODS:
    This multicenter randomized 2-year, double-blind, placebo-controlled study included 612 subjects with a diagnosis of SPMS and an Expanded Disability Status Scale (EDSS) score of 3.5-6.5, stratified according to baseline EDSS score (3.5-5.0, or 5.5-6.5) and HLA haplotype (DR2(+) or DR4(+), or DR2(-)/DR4(-)). Upon entry of 100 DR2(-)/DR4(-) subjects, further study enrollment was limited to DR2(+) or DR4(+) subjects. Subjects were randomly assigned to either 500 mg MBP8298 or placebo, given by IV injection once every 6 months for 2 years. The primary outcome measure was time to progression by ≥1.0 EDSS point (or 0.5 point if baseline EDSS was 5.5 or higher), confirmed 6 months later. Secondary outcomes included mean change in EDSS, mean change in Multiple Sclerosis Functional Composite, MRI changes, annualized relapse rate, and quality of life.

    RESULTS:
    There were no significant differences between treatment groups in either the primary or secondary endpoints. MBP8298 was well tolerated in all treated subjects with no safety issues identified.

    CONCLUSION:
    In the population studied, treatment with MBP8298 did not provide a clinical benefit compared to placebo. Classification of evidence: This study provides Class 1 evidence that MBP8298 is not effective in patients with SPMS who are HLA DR2(+) or DR4(+).


However... a study published in 2012 (see below) showed that it had positive effects in PwSPMS' immune function, e.g., increased CD4(+)CD25(+hi)FoxP3(+) T-cells regulatory T-cells. Thus, the lack of efficacy on EDSS suggests that SPMS may be primarily a neurodegenerative disease rather than an inflammatory disease.


High dose antigen treatment with a peptide epitope of myelin basic protein modulates T cells in multiple sclerosis patients.
Cell Immunol. 2012 Nov;280(1):10-5.

    One of the auto-antigens aberrantly targeted in Multiple sclerosis is myelin basic protein (MBP). In this study, chronic progressive multiple sclerosis (CPMS) patients receiving the experimental drug MBP8298, on a compassionate care trial, were examined before and after high dose peptide treatment for their circulating regulatory T-cell numbers and their responses to the common mitogens, phytohemagglutinin and poke-weed mitogen. Peripheral blood mononuclear cells (PBMCs) isolated from these patients before treatment displayed anergy upon stimulation with phytohemagglutinin; measured through reduced proliferation, IFN-γ and IL-17A secretion in an in vitro cell culture system. 6 Weeks and 6months after treatment their PBMCs displayed a reversal of anergy with phytohemagglutinin stimulation. There was also a marked increase in their CD4(+)CD25(+hi)FoxP3(+) T-cells regulatory T-cells. These results suggest that high dose MBP8298 treatment has a profound effect on the circulating T-cells of CPMS patients, capable of reversing peripheral anergy and establishing T regulation.
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Re: RE DIRUCOTIDE CLINICAL TRIAL FOR SPMS PATINTS

Postby 1eye » Sat Jan 25, 2014 10:05 am

Not only did I experience significant progression but I had a heart attack while on this drug trial.

However, I was on placebo. Just the normal course of the disease when on placebo for two years. Saline cannot cause a heart attack. I was not the only subject very unhappy about the experienced progression, but unblinding would have been unthinkable, so we suffered.

I did not see any very happy campers among my fellow subjects on this trial. If they are still pushing it on people, I am horrified. It was a very large multi-centre trial.

If you have spms, you may be interested in:

Abstract
BACKGROUND:

Human endogenous retrovirus (HERV) genes represent about 8% of the human genome. A member of the HERV family W, the Multiple Sclerosis-Associated Retrovirus (MSRV) gene, encodes an envelope protein (Env), which can activate a proinflammatory and autoimmune cascade through its interaction with Toll-like receptor 4. Due to its proinflammatory property and an inhibitory effect on oligodendrocyte precursor cell differentiation, the MSRV-Env protein could play a crucial role in the pathogeny of multiple sclerosis. GNbAC1 is a humanized monoclonal antibody of the immunoglobulin G4 type, which is directed against MSRV-Env. After validation of the MSRV-Env as a therapeutic target in preclinical experimental models, a clinical development program was initiated.
OBJECTIVE:

This study evaluated the safety profile, pharmacokinetic parameters, and immunogenicity of GNbAC1 in healthy male volunteers.
METHODS:

In this first-in-humans, Phase I, randomized, double-blind, placebo-controlled, dose-escalation study, each subject received a single dose of IV GNbAC1 0.0025, 0.025, 0.15, 0.6, 2, or 6 mg/kg or inactive vehicle (placebo), infused over 1 hour. Tolerability and other laboratory parameters were observed, and regular blood sampling was performed, to study the pharmacokinetic properties and immunogenicity of this monoclonal antibody.
RESULTS:

A total of 33 male subjects (mean age, 44 years) completed the study. GNbAC1 was well tolerated after dosing in all subjects and in each dose cohort. Only minor and nonspecific adverse events (AEs) were recorded; no serious AEs were reported. Pharmacokinetic data show a dose-linear pharmacokinetic profile. The mean elimination half-life ranged between 19 and 26 days, with therapeutically efficient concentrations maintained over a 4-week periods at doses of 2 and 6 mg/kg. No emergence of anti-GNbAC1 antibodies were detected after dosing in any subject over the entire observation period of 64 days.
CONCLUSIONS:

In these healthy male subjects, the safety and pharmacokinetic profiles of GNbAC1 appeared favorable. These findings are expected to allow for the launch of a Phase II development program for this innovative therapeutic approach in patients with multiple sclerosis. ClinicalTrials.gov identifier: NCT01699555.
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