Shepherd Center: Multiple Sclerosis Research

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Multiple Sclerosis Research

The Andrew C. Carlos MS Institute at Shepherd believes that an emphasis on clinical trials and new clinical treatment investigations means the latest treatments are often available to our clients before they are available elsewhere.

The following is a summary of current initiatives for Multiple Sclerosis research at Shepherd Center. Click on indivudual study to learn more.

Correlation of Cognitive Dysfunction and MRI T1 Hypointensities and Corpus Callosum Atrophy in MS Patients (Teva Neuroscience; Ben Thrower, MD, Shepherd Center) [270]

A randomized, rater-blinded, multicenter, parallel-group study comparing the efficacy and safety of Betaseron 250mcg SQ every other day with Avonex 30 mcg IM once per week in RRMS patients previously treated with Avonex (Berlex; Ben Thrower, MD, Shepherd Center) [275]

A Randomized, Controlled, Open-Label Parallel Group Study To Evaluate The Effect Of Regularly Scheduled Neutralizing Antibody Testing On Treatment Patterns Versus Usual Care In High-Dose Interferon Treated Subjects (Ben Thrower, MD, Director MS Institute, Shepherd Center; Fanny Jaquez, MD; Tracy Walker, NP; David Apple, MD; John Lin, MD; Darryl Kaelin, MD; Gerald Bilsky, MD; Laura Schmeier, NP) [392]

A Multi-National, Multi-Center, Randomized, Parallel-Group, Double-Blind Study To Compare The Efficacy, Tolerability, And Safety Of Glatiramer Acetate Injection 40 Mg/Ml And Glatiramer Acetate Injection 20 Mg/Ml Administered Once Daily By Subcutaneous Injection In Subjects With Relapsing Multiple Sclerosis (R-MS) (Ben Thrower, MD, Director MS Institute Shepherd Center; Fanny Jaquez, MD; Tracy Walker, NP; David Apple, MD; John Lin, MD; Darryl Kaelin, MD; Gerald Bilsky, MD; Laura Schmeier, NP) [391]

An open-label extension study of the double-blind, randomized, parallel group, multicenter phase 2 study 307000A to further evaluate the safety and tolerability of Betaseron 500 mcg SQ every other day and Betaseron 250 mcg SQ every other day in patient with RRMS (Berlex; Ben Thrower, MD, Shepherd Center) [276]

A Longitudinal, Case-Control Study To Collect Medical And Epidemiological Data And Blood Samples For Research Into The Causes Of Multiple Sclerosis And Selected Demyelinating Diseases Protocol ACP-001 (Ben Thrower, MD, Fanny M. Jaquez, MD) [378]

Two part study - Phase III patients comparing with relapsing-remitting MS over 104 weeks(Berlex/Division of Schering; Ben Thrower, MD, Shepherd Center) [304]

A Multi-Center, Randomized, Double-Blind, Placebo-Controlled Study Of Subcutaneous Tovaxin™ In Subjects With Clinically Isolated Syndrome Or Relapsing-Remitting Multiple Sclerosis (Ben Thrower, MD, Director of MS Institute, Shepherd Center; Fanny Jaquez, MD; Tracy Walker, NP; Laura Schmeier, NP; David Apple, MD; Gerald Bilsky, MD; John Lin, MD; Darryl Kaelin, MD) [390]

Phase IV, multicenter, open label, randomized study of Rebif44 mcg administered three times per week by subcutaneous injection compared with Copaxoneâ 20mg administered daily by subcutaneous injection in the treatment of relapsing remitting MS (Serono, Inc.; Ben Thrower, MD, Shepherd Center) [308]

A Phase II/III, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Multicenter Study to Evaluate the Safety and Efficacy of Rituximab (MabThera®/ RITUXAN®) in Adults with Primary Progressive Multiple Sclerosis (Genentech, Inc.; Ben Thrower, MD, Shepherd Center) [321]

A Multi-Center, Double-Blind, Randomized Study Comparing the Combines Use of Interferon Beta-1a and Glatiramer Acetate to Either Agent Alone in Patients with Relapsing Remitting Multiple Sclerosis (CombiRx-Phase III)(NIH & NINDS; Ben Thrower MD, Shepherd Center) [325]

A Multi-Centered, Randomized, Double-Blind, Placebo-Controlled Study Assessing the Add-On Effect of Oral Steroids in Relapsing Remitting Multiple Sclerosis subjects treated with Glatiramer Acetate (GA) (Ben Thrower, MD, Shepherd Center) [332]

Double-Blind, Placebo-Controlled, 21-Week, Parallel Group Study to Evaluate Safety and Efficacy of Oral Fampridine-SR (10 mg B.I.D.) in Subjects with Multiple Sclerosis -Protocol No: MS-F203, Version Phase: II (Acorda; Ben Thrower, MD, Shepherd Center) [334]

MS-F203 ECT Open Label Extension Study to Evaluate the Safety, Tolerability and Activity of Oral Fampridine-SR in Subjects with Multiple Sclerosis who Participated in the MS-F203 Trial (Acorda; Ben W. Thrower, MD, David Apple, MD) [334E]

A multicentre, single arm, open-label, phase IIIb study to evaluate the safety and antigenicity of Rebif (IFN-beta-1a) in subjects with relapsing form of multiple sclerosis (Ben Thrower, MD, Shepherd Center) [340]

Implantable Systems Performance Registry (ISPR)(Donald Leslie, MD, Shepherd Center) [346]

A Phase III, Randomized, Double-Blind, Three-Arm, Placebo-Controlled, Multi-Center Study To Evaluate The Safety And Efficacy Of Oral Cladribine In Subjects With Relapsing Remitting Multiple Sclerosis (RRMS)(Eudract No. 2004-005148-28) Protocol #25643 (Ben Thrower, MD, Fanny M. Jaquez, MD) [372]

Correlation of Cognitive Dysfunction and MRI T1 Hypointensities and Corpus Callosum Atrophy in MS Patients (Teva Neuroscience; Ben Thrower, MD, Shepherd Center) [270]

This is a pilot study. Previously published work by the Cleveland Clinic has correlated cognitive dysfunction with MRI lesion load. This same group also demonstrated that brain atrophy and axonal transection occurs in early MS. Filippi, et al demonstrated the treatment affect of Copazone on black holes. The goals of this study are to 1) confirm the correlation of cognitive dysfunction and chronic T1 hypointensity (black hole) volume; 2) confirm the correlation of cognitive dysfunction and corpus callosum area; and 3) confirm a slowing of accumulation of chronic T1 lesion volume and cognitive dysfunction when subjects are evaluated prior to beginning Copaxone and after receiving one year of Copaxone therapy. We propose to show a correlation between cognitive impairment and T1 hypointensity volume and compare the effects of subjects prior to and 1 year after beginning immune-modulating therapy with Copaxone. Copaxoneâ has been used to treat MS patients worldwide since 1997 when it was first made commercially available and the side effects of Copaxone treatment in MS patients are well known.

Multiple Sclerosis (MS) is a chronic, debilitating disease of the central nervous system with either relapsing remitting (RR) or progressive course leading to neurologic deterioration and disability. RR-MS is the most common form of the disease and is characterized by unpredictable acute episodes of neurological dysfunction (relapses), followed by variable recovery and periods of clinical stability. Evidence form a variety of clinical sources indicates that the nerve damage that occurs in MS may happen early in the disease course and that inflammation is associated with this nerve damage. The current therapeutic approaches to MS include symptomatic treatment, acute relapse treatment, and disease modification treatment. The current therapies available target the inflammatory processes of the disease and most are considered to be immunomodulators. Glatiramer Acetate (GA) is the active substance in Copaxone®, a marketed product indicated for the reduction of the frequency of relapses in patients with RR-MS. Previous studies with GA have shown that it significantly effects MRI lesions and relapse rate. Copaxone® contains 20 mg of GA and 40 mg mannitol in water for daily subcutaneous injection. A Phase II study has been conducted with GA 40 mg versus GA 20 mg to determine safety and efficacy of the increased dosage. This was a multi-center, randomized, double-blind parallel group study. The results of this study indicated that there was greater efficacy with the GA 40 mg in comparison to the GA 20 mg to include less enhancing lesions in the MRI, and less relapses. Regarding safety, both dosage levels seemed to be comparable. Tolerability was also similar with the GA 40 mg having a slightly higher incidence of injection site reactions. Overall, there was no clinically significant difference in laboratory tests, ECG recording or vital signs that could be attributed to GA 40 mg. Since the results obtained from this completed Phase II study demonstrated a dose effect favoring the 40 mg dose with an apparently comparable safety profile, the sponsor has decided to proceed with the clinical development program of GA 40 mg. This will be a Phase III study conducted in compliance with the protocol, GCP, and applicable regulatory requirements. The main objective of this study is to compare the efficacy of daily subcutaneous injections of GA 40 mg to that of GA 20 mg (Copaxone®) in RR-MS patients determined by confirmed relapse rates. The primary outcome measure will be the total number of confirmed relapses. Safety and tolerability will also be measured and assessed.

The purpose of this study is to evaluate the effect of regularly scheduled neutralizing antibody testing (NAb) on treatment patterns in physicians treating MS patients with high dose interferons, compared to the usual care of MS subjects receiving high-dose interferon therapy (Betaseron® or Rebif®).

Patients treated with interferons are at risk of developing binding antibodies (BAbs) and neutralizing antibodies (NAbs). Binding antibodies develop in a majority of patients receiving interferons though they do not always disrupt the clinical effect of the interferon treatment. A certain percentage of binding antibodies may be neutralizing antibodies. It has been demonstrated that 40-50% of patients positive for binding antibodies at some point will test positive for neutralizing antibodies. Early detection of binding antibodies may be a useful and cost effective screening method prior to NAbs testing. Neutralizing antibodies have been shown to alter the therapeutic effectiveness of drugs by binding to the receptor and preventing activation, essentially blocking the biological effects of the drug. Development of neutralizing antibodies is more common with high dose interferons. It has been demonstrated that the majority of patients that will become NAb positive do so within 12-18 months of initializing treatment. It is unknown if the benefits of interferons disappear completely in all neutralizing antibody positive patients (regardless of titer) or if the diminished effect is linked to higher titers of neutralizing antibodies.

There is evidence to suggest that interferon treated patients that are NAb positive are clinically compromised demonstrated by MRI outcomes, relapse rates and accumulation of disability. Currently, there are barriers to performing routine NAb testing including cost, accessibility, reimbursement, and lack of guidance on what to do if the test is positive. This study looks to explore the question if removal of these barriers (cost, accessibility, and reimbursement) will change treatment patterns for those taking high dose interferons. If the hypothesis of this study is found to be true, it will support the conclusions of recent guideline publications. These guidelines support the use of NAb testing in the routine management of patients receiving high dose interferons and thus, enhancing the care of MS patients receiving these drugs.

This is a randomized, controlled, open-label, parallel group study. All high dose interferon subjects willing to consent will have blood draws for a Binding Antibody (BAb) and Neutralizing Antibody (NAb) test. Subjects will be randomized to either the Regularly Scheduled NAb Testing Group or the Usual Care Testing Group. Patients randomized to the Regularly Scheduled NAb Testing Group will be scheduled for multiple NAb testing (up to 3 BAb and NAb tests over a 9 month period) with a follow up visit at 12 months. Those randomized to the Usual Care Group will be followed for 12 months under usual care conditions. After the 12 month follow up visit, subjects in the Usual Care Group will be offered access to the BAb +/- NAb test. There will be approximately 2440 subjects randomized over approximately on a 1:1 assignment ratio (1220 subjects per group). Approximately 130 sites will participate in this study.

This study will compare the efficacy, safety and tolerability of RRMS patients converting from treatment with Avonexâ (Interferon b-1a) 30mg intramuscularly once weekly to Interferon b-1b (Betaseronâ) administered subcutaneously every other day with those of patients continuing Avonexâ therapy over a 104-week treatment period. This is a randomized, rater-blinded, multi-center, parallel-group study. The planned sample size is approximately 2000 patients evenly distributed in a randomized fashion between the 2 treatment arms. Approximately 75 centers in the United States will participate.

The main objective of this 24-month open label Phase II study is to further assess the safety and tolerability of Betaseron 500 mcg compared to the standard dose of 250 mcg every other day in patients with RRMS. Patients who complete the initial 12-week double dose trial will be given the option to continue on the study drug for a period of at least 2 years. This multi-center study will include zero to 60 patients in 16 centers throughout the US. There is increasing evidence that the effects of interferon beta 1b on the pathology of MS is closely related, therefore the ongoing safety and efficacy of the 500 mg dose of Betaseron in MS will be studied, and aims to investigate the safety and tolerability of the double dose in preparation for the Phase III (Beyond) study.

A Longitudinal, Case-Control Study To Collect Medical And Epidemiological Data And Blood Samples For Research Into The Causes Of Multiple Sclerosis And Selected Demyelinating Diseases Protocol ACP-001 (Ben Thrower, MD, Fanny M. Jaquez, MD) [378]

The purpose of this study is to establish a collection of blood samples and associated data from approximately 10,000 people, some of whom have experienced at least one CNS demyelinating event characteristic of Multiple Sclerosis (MS), Transverse Myelitis (TM), Acute Disseminated Encephalomyelitis (ADEM), Neuromyelitis Optica (NMO) or Optic Neuritis (ON), their blood relatives (those who have and have not experienced at least one CNS demyelinating event), and unrelated subjects who have not been experienced at least one CNS demyelinating event and who are suitable controls. The samples and data will be made available to scientists who are involved in the study of MS, TM, ADEM, NMO, and/or ON, and in particular, studies involved in determining the causes of these diseases. What is the Accelerated Cure Project for MS? It is a national nonprofit organization dedicated to curing MS by determining its causes. The Accelerated Cure Project believes this effort can be accelerated by organizing the research process and encouraging collaboration between research organizations and clinicians. They are developing a "Cure Map" to establish and document what is known and what is not known about the causes of MS. From the Cure Map, Accelerated Cure Project will facilitate research most likely to reveal the causes of MS in the shortest time through a large-scale, multidisciplinary, blood, tissue, and data bank.

A Multi-Center, Randomized, Double-Blind, Placebo-Controlled Study Of Subcutaneous Tovaxin™ In Subjects With Clinically Isolated Syndrome Or Relapsing-Remitting Multiple Sclerosis (Ben Thrower, MD, Director of MS Institute, Shepherd Center; Fanny Jaquez, MD; Tracy Walker, NP; Laura Schmeier, NP; David Apple, MD; Gerald Bilsky, MD; John Lin, MD; Darryl Kaelin, MD [390]

This is a 52 week study to evaluate the efficacy, safety, and tolerability of autologous Tovaxin™ T Cell Vaccine (TCV) in subject with Clinically Isolated Syndrome (CIS) or Relapsing Remitting Multiple Sclerosis (RRMS). The primary outcome measure for Tovaxin™ treatment of subjects with CIS and RRMS will be the reduction in the number of T1-gadolinium enhancing lesions. Previous studies using TCV (T Cell Vaccine) have proven to be safe and given preliminary evidence of effectiveness. Tovaxin™ has shown to be well tolerated with no reported serious adverse effects to date. Preliminary data from Phase 1 and Phase 2 Studies suggest that the depletion of MRTC (Myelin Reactive T Cells) has the potential to stop progression and perhaps allow the reversal of the disease. The hypothesis is that the elimination of the pathogenic T cells early in the disease will lead to the reversal of disease by allowing remyelination by oligodendroglial cells remaining in MS lesions and restoration of conduction velocity and prevention of an irreversible axonal damage.

Two part study - Phase III patients comparing with relapsing-remitting MS over 104 weeks (Berlex/Division of Schering; Ben Thrower, MD, Shepherd Center) [304]

A two-year study which will compare two different medications for the treatment of MS: Interferon 1b and Copaxone. Both of them have been shown to be safe and effective in treating MS, and both of them are to be given subcutaneously (injected under the skin). The interferon 1b treatment will be administered in two different dosages, the approved standard dose (250 micrograms every other day) and a higher dose (500 micrograms every other day). Copaxone will be administered in its approved dose of 20 mg every day. Interferon 1b 250 micrograms and Copaxone are approved therapies in MS treatment whereas interferon 1b 500 micrograms is experimental and will be tested in this study. If all the results of the screening are satisfactory, volunteers will be randomly assigned to one treatment group. Volunteers will be asked to fill in three questionnaires concerning the impact of MS on their daily life followed by a general physical examination and the evaluating physician will perform a standardized neurological examination.

The primary objective of the study is to compare the time to first relapse in subjects treated with Rebif 44mcg three times per week with that of subjects treated with Copaxone 20mg daily during 96 weeks of treatment. The main secondary objective of the study is to compare the mean number of T2 active lesions, defined as new or enlarging T2 lesions, per subject per scan during 96 weeks of treatment with Rebif 44 mcg three times per week with Copaxone 20mg daily. Safety and efficacy data will be obtained through repeated neurological examinations, MRI scans, routine clinical follow-up, routine hematology, clinical chemistry, urinalysis, determination of titre of antibodies to study drug, and monitoring of adverse events. The primary outcome measure will be the time to first relapse during 96 weeks of therapy with either agent. The main secondary outcome measure will be the mean number of T2 active lesions per subject per scan during 96 weeks of treatment. The other secondary outcome measure is the time to confirmed disability progression. Other outcome measures will be relapse rate, proportion of subjects who are relapse-free, proportion of subjects with confirmed disability progression, change in brain volume and number of new T1-hypointense lesions. This will be an open-label, randomized, multicenter, comparative, parallel-group study with a neurologist blinded to treatment for assessing neurologic exams and a neuro-radiologist blinded to treatment for assessing central MRI evaluations. Subjects will be treated for 96 weeks. This study will compare the therapeutic effect of high dose, high frequency IFN beta-1a therapy to glatiramer acetate for relapsing-remitting MS. Six hundred and sixteen interferon and glatiramer acetate-naïve subjects will be enrolled who have definite relapsing-remitting multiple sclerosis (RRMS) with Expanded Disability Status Score (EDSS) of 0 to 5.5 and who have clinically active disease, defined as having one or more relapses in the prior two years.

The purpose of this research is to investigate the effectiveness and safety of rituximab in the treatment of primary progressive MS as compared to a placebo in adults as measured by confirmed disease progression over a 96-week treatment period. Follow-up will continue for 120 weeks. This study consists of four periods: screening, pretreatment, treatment, and follow-up. Participants can be part of an additional research that uses blood, cerebrospinal fluid, and urine samples to determine information about the development and progression of MS. These samples may be helpful in learning about the use of rituximab in treating MS and may help develop new theories or diagnostic tests. Participants who enter this portion of the study will undergo additional lab assessments throughout the course of the study. Other labs to be done at various times through this study include: complete blood count (CBC); serum chemistries; urine pregnancy test; serum pregnancy test; urinalysis for blood, protein, and glucose; thyroid test; serum pharmacokinetic samples; Human Anti-Chimeric Antibody (HACA); immune panel; whole blood samples for FACS-B analysis. During follow-up assessments, subjects will have their B cells measured. If their B-cells do not return to normal by week 122, these participants will have their B-cells monitored every 6-8 weeks.

A Multi-Center, Double-Blind, Randomized Study Comparing the Combines Use of Interferon Beta-1a and Glatiramer Acetate to Either Agent Alone in Patients with Relapsing Remitting Multiple Sclerosis (CombiRx-Phase III) (NIH & NINDS; Ben Thrower MD, Shepherd Center) [325]

The purpose of this study is to determine whether the combination of interferon beta-1a (Avonex) and glatiramer acetate (Copaxone) is an effective therapy for Relapsing-Remitting Multiple Sclerosis. One thousand participants will be placed in one of three groups. Group A (250 participants) will be given interferon beta-1a and placebo glatiramer acetate. Group B (250 participants) will be given placebo interferon beta-1a and glatiramer acetate. Group C (500 participants) will be given interferon beta-1-a and glatiramer acetate. Participants will be asked to come for approximately 14 scheduled study visits. As no large scale, pivotal trials for new agents is underway at present for this disease, it would be efficacious to improve the current state of MS therapy by combining current therapies. This is the basic foundation for the study. There are also other objectives of this study: confirmed progression on the Expanded Disability Status Scale (EDSS), change in the Multiple Sclerosis Functional Composite, and a change in the Z4 composite on the MRI. Tertiary endpoints include quality of life measures and cost effectiveness measures (including steroid use and hospitalizations).

The primary objective of the study is to evaluate the add-on treatment effect of oral steroids on brain volume changes as measured by the 3-year change from baseline in brain volume, in relapsing remitting multiple sclerosis subjects treated with GA. Secondary Objectives: secondary efficacy endpoints will evaluate the add-on treatment effect of oral steroid over the GA on additional MRI metrics and clinical endpoints. This research study is to determine whether glatiramer acetate (Copaxone) and the add-on treatment of prednisone is safe and more effective than the treatment with glatiramer acetate and placebo (an inactive substance) in subjects diagnosed with the relapsing form of multiple sclerosis.

This study will evaluate the clinical efficacy and safety of oral Fampridine-SR 10mg b.i.d. versus placebo in the treatment of lower extremity motor dysfunction, as evidenced by walking speed and leg strength in subjects with clinically defined multiple sclerosis (MS). This is a multi-center, randomized, double blind, placebo-controlled, paralleled group study. The study involves a 2 week placebo run-in period, a 14 week randomization treatment period and a 4 week final follow up period. Subjects will have a 50% chance of receiving Fampridine or placebo, and neither the subject nor study personnel will know the group assignments. The tests that will be involved in this study are a muscle strength test, a Timed 25 Foot Walk, Ashworth evaluation, laboratory testing from blood and urine samples, EEG, ECG and questionnaires. Participants will be asked to come to the study for approximately 10 visits. Other MS drugs are permitted while on this study (i.e. Betaseron, Copaxone, Rebif, or Avonex). Exclusions for this study are prior exposure or treatment with Fampridine or any past history of seizures.

MS-F203 ECT Open Label Extension Study to Evaluate the Safety, Tolerability and Activity of Oral Fampridine-SR in Subjects with Multiple Sclerosis who Participated in the MS-F203 Trial (Acorda; Ben W. Thrower, MD, David Apple, MD) [334E]

The objective of this extension study is to evaluate the safety, tolerability and activity of Fampridine-SR when administered for up to 36 additional months in subjects who previously participated in Acorda Therapeutics Protocol MS-F203. Subjects are eligible regardless of whether they received active drug or placebo during their participation in MS-203, provided they completed participation in the study.

A multicentre, single arm, open-label, phase IIIb study to evaluate the safety and antigenicity of Rebif (IFN-beta-1a) in subjects with relapsing form of multiple sclerosis (Ben Thrower, MD, Shepherd Center) [340]

The purpose of this study is to evaluate the safety and compare the antigenicity of the new FBS-free/HSA-free Rebif formulation (RNF) to historical data. As has been seen with other recombinant protein molecules, the use of injectable recombinant proteins may result in the development of neutralizing antibodies (NAbs). Antibodies are considered neutralizing by their ability to inhibit the biological effect of interferon in the bioassay system. This study has worked to improve the formulation of IFN beta-1a to reduce aggregate levels and to develop a formulation that is HSA-free. Reducing aggregates should reduce antigenicity of the product while removal of HSA may have an unpredictable effect on antigenicity. This study will assess the immunogenicity and safety of the new HSA free formulation, manufactured using IFN-beta-1a drug substance produced by a new clone from the FBS-free process. The design of this study assumes that the Phase 1 tolerability and PK data of the selected formulation is similar to the currently approved HSA-containing formula. Subjects who complete the full 96 weeks of the study without any ongoing effects, will at week 96, not have to undergo the Week 100 visit.

Implantable Systems Performance Registry (ISPR) (Donald Leslie, MD, Shepherd Center) [346]

The purpose of this registry is to monitor the use and performance of Medtronic products and to better understand patient needs. Medtronic will use the information from this registry to improve its products or develop possible new products and therapies. Medtronic will also use the information to follow government regulations regarding product monitoring and safety. Information collected in the registry will be maintained indefinitely. The database is expected to collect information on devices implanted in over 500 new patients every year, and to continue collecting data as long as the patients receive therapy with the devices, or as long as the patient agrees to participate in the registry. This registry is ongoing with continuous enrollment and no pre-determined sample size goal. Patients who provide informed consent may be involved in this registry. The devices and therapy received will be exactly the same as if the patient did not participate. The research involved in this registry includes data collection only and this data should be available from the patient's medical record.

A Phase III, Randomized, Double-Blind, Three-Arm, Placebo-Controlled, Multi-Center Study To Evaluate The Safety And Efficacy Of Oral Cladribine In Subjects With Relapsing Remitting Multiple Sclerosis (RRMS) (Eudract No. 2004-005148-28) Protocol #25643 (Ben Thrower, MD, Fanny M. Jaquez, MD) [372]

The purpose of this study is to give oral cladribine at different doses (low or high dose), to two groups of study subjects, to see how safe and effective it is. Treatments will be compared to a third group of study subjects who will be given placebo. Oral cladribine works by decreasing the number of cells circulating in the blood that would otherwise attack the nervous system and create the symptoms typical of MS. Cladribine, in an intravenous form, has been approved and marketed by another company since 1993 for the treatment of two types of cancers. Serono International, together with IVAX, has developed an oral form of cladribine to be tested in RRMS. The oral form that will be tested in this clinical study.