Safety, Tolerability, and Effectiveness of CGP77116 in Patients With Multiple Sclerosis (MS)
Safety, Tolerability, and Effectiveness of CGP77116 in Patients With Multiple Sclerosis (MS)
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
 immunological studies.

 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 relapsing-remitting
 MS.

 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
 requirements.