Please select the eligibility criteria that correspond to the clinical trial below.
Title: International, Multicenter, Phase IIIb Study of Subcutaneous Every-other-day Treatment of Patients With Relapsing Multiple Sclerosis With (Phase A): Double-blind Betaseron/Betaferon 250µg or 500µg or Open-label Betaseron/Betaferon 250µg and (Phase B): Open-label Betaseron/Betaferon 500µg
Brief Summary: The BEYOND Follow-Up study will give patients who participated in the preceding BEYOND study the opportunity to continue treatment with the 500µg dose of interferon beta (IFNB) 1b and will further investigate the safety and tolerability profile of interferon beta 1b 500µg during longer-term treatment.


Options:
A: Inclusion Criteria:

* Male and female subjects between the ages of 18 and 60 years, inclusive.
* Diagnosis of relapsing-remitting MS by either the Poser or McDonald criteria.
* Expanded Disability Status Scale (EDSS) score between 0 and 5.5, inclusive.
* At least 2 exacerbations in the prior three years; one exacerbation may utilize the McDonald MRI criteria for dissemination in time (a new gadolinium \[Gd\]-enhancing lesion demonstrated on a scan done at least 3 months following onset of a clinical attack or a new T2 lesion or Gd-enhancing lesion on a follow-up scan after an additional 3 months).
* Give written informed consent prior to any testing under this protocol, including screening tests and evaluations that are not considered part of the subject's routine care.

Exclusion Criteria:

* Any prior use of interferon beta or glatiramer acetate.
* Acute exacerbation within 30 days of screening.
* Steroids for acute exacerbations (\>100 mg/day) within 30 days of study entrance or chronic systemic steroid use.
* Evidence of progressive MS.
* Use IVIg, azathioprine, methotrexate, cyclosporine, mitoxantrone, cyclophosphamide, mycophenolate (CellCept) or plasma exchange in the twelve weeks prior to study drug dosing.
* Any previous treatment with natalizumab (Tysabri, Antegren), cladribine, T cell vaccine, Campath, daclizumab, rituximab, altered peptide ligand or total lymphoid irradiation.
* Treatment with 4 aminopyridines in the four weeks prior to study drug dosing.
* Prior treatment with any other investigational drug, unless approved by the Clinical Coordinating Center (Dr. Lublin).
* Inability to perform the baseline MSFC (timed 25-foot walk, 9-hole peg test \[9HPT\], and Paced Auditory Serial Addition Test 3 \[PASAT3\]).
* Inability to undergo baseline MRI scan.
* History of any significant cardiac, hepatic, pulmonary, or renal disease, immune deficiency, or other medical conditions that would preclude therapy with interferon beta, glatiramer acetate, or participation in this study.
* Known history of sensitivity to gadopentetate dimeglumine or mannitol.
* History of a seizure within the 3 months prior to randomization.
* History of suicidal ideation or an episode of severe depression within the 3 months prior to randomization.
* Abnormal screening blood tests exceeding any of the limits defined below:

  * Alanine transaminase (ALT) or aspartate transaminase (AST) greater than two times the upper limit of normal (i.e., \>2 × ULN)
  * Total white blood cell count \<2,300/mm3
  * Platelet count \<80,000/mm3
  * Creatinine \>2 × ULN
* Participation in another experimental clinical trial, without formal approval.
* History of alcohol or drug abuse within the 2 years prior to randomization.
* Female subjects who are currently pregnant, breast-feeding, or plan to become pregnant.
* For female subjects, unless postmenopausal or surgically sterile, unwillingness to practice effective contraception, as defined by the investigator, during the study. The rhythm method is not to be used as the sole method of contraception.
* Unwillingness or inability to comply with the requirements of this protocol including the presence of any condition that is likely to affect the subject's returning for scheduled follow-up visits on schedule (any physical, mental, or social condition).
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:

* 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.
D: Inclusion Criteria:

* Female and male patients
* Aged 18-55 years
* Diagnosis of RRMS (Relapsing-Remitting Multiple Sclerosis), EDSS score of 0 to 5.0
* Treatment-naive to IFNB or Copaxone

Exclusion Criteria:

* Neurological progression at disease onset or between relapses
* Serious or acute heart diseases
* History of severe depression or suicide attempt
* Serious or acute liver, renal or bone marrow dysfunction
* Monoclonal gammopathy
* Known allergy to Gadolinium-DTPA, to IFNs (Interferons), to glatiramer acetate, to human albumin or to mannitol
* Pregnancy or lactation

Answer: B