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: Key Inclusion Criteria:

* Capable of understanding and complying with the protocol
* Has a confirmed diagnosis of RRMS
* Neurologically stable with no evidence of relapse within 30 days prior to randomization
* Agrees to use an acceptable method of contraception for the duration of the study and for 30 days after any study drug administration, or is surgically sterile or post-menopausal

Key Exclusion Criteria:

* Have any finding(s) that would compromise the safety of the subject, affect the subject's ability to adhere to the protocol visit schedule or to fulfill visit requirements, or would make the subject unsuitable for participation in the study
* Diagnosis of primary progressive, secondary progressive, or progressive relapsing MS
* History of clinically significant cardiovascular, pulmonary, GI, dermatologic, psychiatric, neurologic (other than MS), endocrine, renal, and/or other major disease that would preclude participation in a clinical trial
* History of GI surgery (except appendectomy that occurred more than 6 months prior to screening
* History of clinically significant recurring or active gastrointestinal symptoms (eg, nausea, diarrhea, dyspepsia, constipation) within 3 months of screening
* Chronic use (7 days) of medical therapy to treat any GI symptoms within 1 month of screening Has a clinically significant medical condition or observed abnormality at screening
* History of a myocardial infarction, including a silent myocardial infarction or unstable angina
* History of clinically significant drug or alcohol abuse within the past year prior to screening
* Clinically significant history of suicidal ideation or suicidal behavior in the last 12 months
* Subject is pregnant or breastfeeding or plans to become pregnant or begin breastfeeding at any point during the study and for 30 days after any study drug administration
* Prior use of Dimethyl Fumarate (DMF)

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
B: 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.
C: Inclusion Criteria:

* Single, first clinical event suggestive of MS within 60 days prior to study Day 1, which is the day of randomization (clock starts 24 hours after onset). The event must be a new neurological abnormality present for at least 24 hours, either mono- or polysymptomatic, other than a paresthesia, vegetative or cerebral dysfunction
* At least two clinically silent lesions on the T2-weighted MRI scan, with a size of at least 3 millimeter (mm), at least one of which is ovoid or periventricular or infratentorial
* EDSS 0 - 5.0 at least one time point during the screening period before start of treatment
* 18 and 50 years old, inclusive
* Willing to follow study procedures
* Written informed consent
* If female, subject must:

  * be neither pregnant nor breast-feeding nor attempting to conceive
  * use a highly effective method of contraception. A highly effective method of contraception is defined as those which result in a low failure rate (that is \[i.e.\] less than 1 percent \[%\] per year) when used consistently and correctly such as implants, injectables, combined oral contraceptives, some intrauterine devices (IUDs), sexual abstinence or vasectomised partner

Exclusion Criteria:

* Diagnosis of MS (per McDonald criteria 2005)
* Any other disease that could better explain the subject's signs and symptoms
* Complete transverse myelitis or bilateral optic neuritis
* Subject uses or has used any other approved MS disease-modifying drug (DMD)
* Any investigational drug or undergone an experimental procedure within 12 weeks prior to study Day 1
* Oral or systemic corticosteroids or adrenocorticotropic hormone (ACTH) within 30 days prior to study Day 1
* Total bilirubin greater than 2.5 times upper limit of normal (ULN)
* Subject has total aspartate aminotransferase (AST) or alanine aminotransferase (ALT) or alkaline phosphatase (ALP) greater than 2.5 times the ULN
* Inadequate bone marrow reserve, defined as a total white blood cell count less than 3.0 x 109 per liter (/L), platelet count less than 75 x 109/L, hemoglobin less than 100 gram per liter (g/L)
* Current autoimmune disease
* Major medical or psychiatric illness (including history of or current severe depressive disorders and/or suicidal ideation) that in the opinion of the investigator creates undue risk to the subject or could affect compliance with the study protocol
* History of seizures not adequately controlled by treatment
* Cardiac disease, such as angina, congestive heart failure or arrhythmia
* Known allergy to IFN-beta or the excipient(s) of the study medication
* Any condition that could interfere with the MRI evaluation;
* Known allergy to gadolinium-diethylene triamine pentaacetic acid (DTPA)
* Previously participated in this study
* Participated in any clinical trial within the past 6 months
* Any immunomodulatory or immunosuppressive therapy at any time prior to enrollment, including, but not limited to, the following products: any IFN, glatiramer acetate (Copolymer I), cyclophosphamide, cyclosporine, methotrexate, linomide, azathioprine, mitoxantrone, teriflunomide, laquinimod, cladribine, total lymphoid irradiation, anti-lymphocyte monoclonal antibody treatment (e.g. natalizumab, alemtuzumab/Campath, anti-cluster of differentiation 4 \[CD4\]), intravenous, immunoglobulins (Igs), cytokines or anti-cytokine therapy
* Any experimental MS treatment prior to trial entry, including, but not limited to, any statins (if given to prevent MS) and pentoxyfylline
* History of alcohol or drug abuse
* Intolerance or any contraindication to both paracetamol (acetaminophen) and ibuprofen
* Inability to administer subcutaneous injections either by self or by caregiver
* Moderate to severe renal impairment
D: Inclusion Criteria:

* Males and females between 18 and 60 years of age
* Female subjects must be neither pregnant nor breast-feeding and must lack child-bearing potential, as defined by either: post-menopausal or surgically sterile or use an effective method of contraception for the duration of the study
* Have Relapsing Remitting Multiple Sclerosis (RRMS) according to the revised McDonald criteria 2005
* Have brain and/or spinal MRI with findings typical of Multiple Sclerosis (MS)
* Have disease duration for more than 12 months
* Have disease activity characterized by at least one clinical event and one or more Gadolinium-enhancing MRI lesions within the 6 months prior to randomization
* Have score of \<=5.5 on the Expanded Disability Status Scale (EDSS)
* Be willing and able to comply with the protocol for the duration of the study
* Have given written informed consent prior to any study-related procedure not part of the normal medical practice

Exclusion Criteria:

* Have any disease other than MS that could better explain his/her signs and symptoms
* Have complete transverse myelitis or bilateral optic neuritis
* Have received or have used anytime monoclonal antibodies, mitoxantrone, cytotoxic or immunosuppressive therapy (excluding systemic steroids and adrenocorticotrophic hormone \[ACTH\]), or total lymphoid irradiation
* Have received within 3 months prior to baseline any approved disease-modifying therapy for MS, cytokine or anti-cytokine therapy, intravenous immunoglobulin, plasmapheresis, any investigational drug, or experimental procedure
* Have received within 30 days prior to baseline oral or systemic corticosteroids or ACTH
* Other protocol defined exclusion criteria could apply

Answer: B