Multiple sclerosis (MS) is a disease of the nervous system. The exact cause of MS is
unknown, but it is believed to be an autoimmune condition. Autoimmune conditions are
diseases that cause the body's immune system and natural defenses to attack healthy cells.
In the case of MS, the immune system begins attacking myelin, the cells that make up the
sheath covering nerves. Without myelin nerves are unable to transmit signals effectively
and symptoms occur.
Researchers are interested in testing the safety, tolerability, and effectiveness of a new
therapy (CGP77116) for Multiple Sclerosis (MS). CGP77116 is a small protein similar to the
protein in myelin. CGP77116 is designed to modify the immune reaction that destroys normal
myelin. CGP77116 is an experimental therapy meaning it has not been approved by the U.S.
Food and Drug Administration. However, in preliminary studies on animal it has been shown
to be effective at modifying the autoimmune reaction associated with the development of MS.
The purpose of this study is to assess the safety and effect of CGP77116 on disease activity
in patients with Multiple Sclerosis as measured by magnetic resonance imaging (MRI) and
The study is broken into three parts:
I) BASELINE: in the first part of the study patients will undergo 6 MRIs over a 5 month
period. During this time, patients will be evaluated based on the presence of MS lesions
seen on MRI. Patients whose MS lesions are highly active will be entered into the second
part of the study.
II) TREATMENT: in the second part of the study, patients with active MS lesions will begin
receiving CGP77116. The drug will be given by injection once a week for one month and then
once a month for 8 additional months.
III) FOLLOW-UP: in the third and final part of the study, patients will undergo an MRI
every 2 months for 6 months and then every 3 months for 6 additional months. The results of
the MRIs will be used to measure the effectiveness of CGP77116.
This trial will evaluate safety, tolerability and effect on cranial magnetic resonance
imaging (MRI) and immune response of CGP 77116 in patients with the demyelinating autoimmune
disease, multiple sclerosis (MS). The purpose of the trial is to assess whether CGP 77116
modifies inflammatory disease activity as measured by MRI and immunological techniques, and
to facilitate dose selection for future pivotal trials in progressive and
CGP 77116 is an altered peptide ligand (APL) designed around an immunodominant epitope of
human myelin basic protein (MBP) corresponding to amino acids 83-99, for the treatment of
multiple sclerosis (MS). Substitution of a key T cell receptor contact residue with alanine
results in a non-stimulatory peptide analogue. Recent evidence suggests that a T
cell-mediated immune response against immunodominant myelin protein peptides such as MBP
(83-99) is involved in MS pathogenesis (1). MS results when the immune system is unable to
keep autoreactive T cells from entering the central nervous system where they initiate
demyelination of myelin sheaths. By targeting MBP autoreactive T cells, CGP 77116 may
downregulate the MBP-specific immune response and lead to amelioration of MS.
Patients with clinically definite and/or laboratory-supported definite diagnosis of MS.
Patients must have had a minimum of 6 monthly MRI scans prior to randomization according
to a standardized MRI protocol and fulfill the pre-defined MRI criteria of disease
activity: mean of at least 0.5 total gadolinium-enhancing lesion in the 6 monthly scans
immediately preceding randomization.
No evidence of relapse for at least 30 days prior to entry.
One or more relapses in the 2 years preceding randomization.
Expanded Disability Status Scale (EDSS) score less than or equal to 7.0.
Male or female aged 18 to 55 years.
Females must be either post-menopausal, surgically incapable of bearing children, or
practicing a medically accepted method of birth control.
Patients willing and able to give informed consent according to national legal