Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Multinational, Multicenter, Randomized, Double-Blind, Placebo Controlled, Parallel Group Study to Evaluate the Effect of Early Glatiramer Acetate Treatment in Delaying the Conversion to Clinically Definite Multiple Sclerosis (CDMS) of Subjects Presenting With Clinically Isolated Syndrome (CIS)
Brief Summary: The primary objective is to assess the effect of treatment with glatiramer acetate (GA) compared to placebo on the time to conversion to CDMS, as determined by Poser criteria (the occurrence of the second clinical attack) during the double-blind period. The secondary objective is to assess, within the time frame of the up to 3-year double-blind, placebo-controlled study period, the effect of GA on clinical and Magnetic Resonance Imaging (MRI) parameters. The long-term objectives of the study (exploratory in nature) are to assess, within the time frame of 5 years, the neuroprotective effect of early versus delayed treatment with GA as reflected by clinical and MRI parameters measuring the accumulated irreversible brain tissue damage.

A pre-planned interim analysis was performed on all efficacy and safety data accumulated in the database up to October 14, 2007, i.e. when 81% of exposure to treatment in the double-blind, placebo-controlled period had been collected. Upon review of the interim analysis results, the Data Monitoring Committee (DMC) recommended that the double-blind portion of the study be stopped and that subjects be switched to the 2-year Open-label period, during which time they would have the option of receiving GA therapy. The sponsor (Teva) adopted the DMC recommendations and took the necessary action towards its implementation.


Options:
A: Inclusion Criteria:

* Be between 18 and 60 years of age
* Have definite relapsing multiple sclerosis
* Have had one or more relapses within the prior 12 months
* Must be in a clinically stable or improving neurological state during the four weeks prior to Study Day 1
* Expanded Disability Status Scale (EDSS) score from 0 to 5.5, inclusive
* If female, she must either be post-menopausal or surgically sterilized; or use a hormonal contraceptive, intra uterine device, diaphragm with spermicide, or condom with spermicide, for the duration of the study; and be neither pregnant nor breast-feeding
* Confirmation that the subject is not pregnant must be established by a negative serum human chorionic gonadotropin (hCG) pregnancy test within 7 days of Study Day 1 and a negative urine pregnancy test on Study Day 1. A pregnancy test is not required if the subject is post-menopausal or surgically sterilized
* Be willing and able to comply with the protocol for the duration of the study
* Voluntarily provide written informed consent and, for USA sites only, a subject authorization under Health Insurance Portability and Accountability Act (HIPAA), prior to any study-related procedure that is not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to their future medical care

Exclusion Criteria:

* Have secondary progressive multiple sclerosis (SPMS) or primary progressive MS (PPMS)
* Prior use of any interferon or glatiramer acetate
* Have had treatment with oral or systemic corticosteroids or adrenocorticotrophic hormone (ACTH) within 4 weeks of Study Day 1 and within 7 days prior to the Day 1 magnetic resonance imaging (MRI)
* Have a psychiatric disorder that is unstable or would preclude safe participation in the study.
* Have significant leukopenia (white blood cell count \< 0.5 times the lower limit of normal of the central laboratory) within 7 days of Study Day 1.
* Have elevated liver function tests (alanine aminotransferase \[AST\], aspartate aminotransferase \[ALT\], alkaline phosphatase \> 2.0 times the upper limit of normal \[ULN\] of the central laboratory, or total bilirubin \> 1.5 times the ULN of the central laboratory) within 7 days of Study Day 1 or a history of hepatitis (including infectious or drug-induced)
* Prior cytokine or anti-cytokine therapy within 3 months prior to Study Day 1
* Prior use of immunomodulatory or immunosuppressive therapy (including but not limited to cyclophosphamide, cyclosporin, methotrexate, azathioprine, linomide, mitoxantrone) within the 12 months prior to Study Day 1
* Prior use of cladribine or have received total lymphoid irradiation
* Have allergy or hypersensitivity to human serum albumin, mannitol, glatiramer acetate, natural or recombinant interferon-β, or any other components of the study drugs or gadolinium diethylenetriaminepentaacetic acid
* Have taken intravenous immunoglobulin or any other investigational drug or taken part in any experimental procedure in the 6 months prior to Study Day 1.
* Presence of systemic disease that might interfere with subject safety, compliance or evaluation of the condition under study (e.g. insulin-dependent diabetes, Lyme disease, clinically significant cardiac disease, human immunodeficiency virus \[HIV\], human T-cell lymphotrophic virus type I \[HTLV-1\])
* Have had plasma exchange in 3 months prior to Study Day 1.
B: Inclusion Criteria:

* Completion of the BEYOND study 306440 as scheduled
* Relapsing multiple sclerosis
* Medical assessment by the investigator that there is no objection to the patient's participation in this trial considering the medical experience from study 306440. Special attention should be given to laboratory abnormalities and clinically relevant liver, renal and bone-marrow dysfunction.
* Females of child-bearing potential:

  * Agreement to practice adequate contraception methods and
  * Negative pregnancy test and
  * No lactation
* Written informed consent

Exclusion Criteria:

* Serious or acute heart diseases
* History of severe depression or suicide attempt
* Epilepsy not adequately controlled by treatment
* Known allergy to IFNs, to human albumin or to mannitol
* Medical, psychiatric or other conditions that compromise the patient's ability to understand the patient information, to give informed consent, to comply with the trial protocol, or to complete the study
C: Inclusion Criteria

Patients may be eligible for this study if they:

* Have been diagnosed with RR-MS, within 2 years of diagnosis.
* Are 18-55 years old.
* Have RR-MS with evidence of demyelination on MRI scanning of the brain.
* Have extended disability status scale (EDSS) scores between 0 and 3.5.
* Have not taken Copaxone or oral myelin.
* Have not had immunomodulating therapy for the past 3 months.
* Have not taken immunosuppressants.
* Have not had steroid treatment 1 month before entry.
* Have no evidence of active infection or cancer.

Exclusion Criteria

Patients may not be eligible for this study if they:

* Have a normal brain MRI.
* Are not willing to practice contraception (applies to women who are able to have children).
* Are pregnant or breast-feeding.
* Are currently taking any of the following drugs: beta2-adrenergic agonist or antagonist, diuretics, tricyclic antidepressants, or monoamine oxidase inhibitors.
* Have heart, blood, liver, or kidney problems.
* Have a disease that affects blood clotting or lung function.
* Have abnormalities that relate to the endocrine system.
* Have a history of alcohol or drug abuse within 6 months of enrollment.
* Have been diagnosed with primary progressive MS, in which the disease slowly worsens without periods of recovery.
D: Inclusion Criteria:

1. The subject must have undergone a single clinical attack.
2. The subject must have a unifocal clinical presentation.
3. The subject should be enrolled within the period of 90 days after onset of a single unifocal clinical attack (index attack).
4. There must be 2 or more cerebral lesions highly suspicious of multiple sclerosis (MS) on the screening Magnetic Resonance Imaging (MRI), measuring 6mm or more in diameter.
5. Subjects must be between the ages of 18 and 45 years inclusive.
6. Subjects must not have taken corticosteroids within the 30 days prior to the MRI at the baseline visit.
7. Subjects may be male or female. Women of child-bearing potential must practice a medically acceptable method of birth control. Acceptable methods include oral contraceptive, contraceptive patch, long-acting injectable contraceptive, or double-barrier method (condom or intrauterine device with spermicide).
8. The subjects must be willing and able to give written informed consent, prior to entering the study.

Exclusion Criteria:

1. Multifocal clinical presentation.
2. Diseases other than MS responsible for the clinical/MRI presentation. The following laboratory tests must be part of the subject's medical history for differential diagnosis of clinically isolated syndrome (CIS): erythrocyte sedimentation rate (ESR), antinuclear antibody (ANA), complement (C3, C4) and anticardiolipin IgG - IgM. In the event that the results of these tests are inconclusive, the following additional tests may be requested by the Eligibility Evaluation Committee: syphilis screening, vitamin B12 and folic acid. In the case of spinal cord CIS presentation, a spinal cord MRI is required for confirmation of diagnosis in the medical history of the subject.
3. Use of experimental or investigational drugs, including IV immunoglobulin, and/or participation in an investigational drug study within 6 months prior to study entry.
4. Use of interferon agents within 6 months prior to the screening visit.
5. Chronic corticosteroid treatment (more than 30 consecutive days) in the 6 months prior to study entry.
6. Pregnancy or breast feeding.
7. Subjects who experience a relapse between the screening (month -1) and baseline (month 0) visits.
8. Life-threatening or other clinically significant disease.
9. A medical or psychiatric condition that affects the subject's ability to give informed consent, or to complete the study, or if the subject is considered by the treating neurologist/physician to be, for any other reason, an unsuitable candidate for this study.
10. A known history of sensitivity to mannitol.
11. A known history of sensitivity to gadolinium.
12. Inability to successfully undergo MRI scanning.

Answer: D