Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Multi-Center, Double-Blind, Randomized Study Comparing the Combined Use of Interferon Beta-1a and Glatiramer Acetate to Either Agent Alone in Patients With Relapsing-Remitting Multiple Sclerosis (CombiRx)
Brief Summary: This is for a randomized clinical trial (RCT) to determine if the combined use of interferon beta-1a (IFN) and glatiramer acetate (GA) is a measurably better therapy than either agent used individually in patients with relapsing-remitting (RR) multiple sclerosis (MS).


Options:
A: Inclusion Criteria:

* Diagnosis of MS as defined by McDonald et al, criteria, # 1- 4
* Between the ages of 18 and 55, inclusive
* Baseline EDSS score between 0.0 and 5.0, inclusive
* Have been treated with Avonex for at least the 12 months prior to randomization
* Have experienced at least one relapse (while on Avonex) within the 12 months prior to randomization.
* Cranial MRI scan demonstrating lesions consistent with MS.
* Have given written informed consent to participate in the study.

Exclusion Criteria:

* Primary progressive, secondary progressive, or progressive relapsing MS.
* MS relapse has occurred within 50 days of randomization
* A clinically significant infectious illness within 30 days prior to randomization
* History of, or abnormal lab result, indicative of significant disease, that in the opinion of the investigator, would preclude the administration of a recombinant humanized antibody immunomodulating agent or Avonex for 116 weeks.
* History of severe allergic or anaphylactic reactions or known drug hypersensitivity.
* Unable to perform the Timed 25-Foot Walk, 9HPT and PASAT 3
* Abnormal blood tests at Screening Visit
B: Inclusion Criteria:

* Participation in study 28063.
* Completion of Week 36 visit of the core study 28063.
* Willingness and ability to comply with study procedures for the duration of the study.
* Voluntary provision of written informed consent (including, for the USA, subject authorization under the Health Insurance Portability and Accountability Act (HIPAA)), given before any study-related procedure that is not part of normal medical care and with the understanding that the subject may withdraw consent at any time without prejudice to his or her future medical care.

Exclusion Criteria:

* Premature discontinuation of core study 28063.
* Subjects who meet criteria listed below will receive IMP in study 28851:

  * Subjects who are eligible for participation in extension study 28851 but do not meet these criteria will not be treated with IMP but will undergo scheduled visits, irrespective of their treatment.
* All subjects must satisfy the following criteria before Extension Study Day 1 (D1-EXT; defined as the first day of dosing in the extension study) to be eligible for treatment with IMP:

  * Eligibility for participation in extension study 28851.
  * For women of childbearing potential, a negative urine pregnancy test at eligibility assessment.
  * Female subjects of childbearing potential must be willing to avoid pregnancy by using an adequate method of contraception for four (4) weeks before the first dose administered within the extension study, during the study and for twelve (12) weeks after the last dose of trial medication. Adequate contraception is defined as two barrier methods, or one barrier method with spermicide, or an intrauterine device, or use of a combined oral female hormonal contraceptive (or the definitions requested by health authorities and locally amended in the core study 28063). For the purposes of this trial, women of childbearing potential are defined as: "All female subjects after puberty unless they are post-menopausal for at least two years or are surgically sterile" (For Germany Only: Female subjects of childbearing potential must be willing to avoid pregnancy by using highly effective methods of contraception for approximately four (4) weeks prior to D1-EXT, during and for twelve (12) weeks after the last dose of trial medication. This requirement does not apply to surgically sterile subjects or to subjects who are postmenopausal for at least 2 years. Highly effective contraception is defined as any method or combination of methods which result in a low failure rate (i.e. less than (\<) 1% per year) when used consistently and correctly, such as implants, injectables, combined oral contraceptives, sexual abstinence, vasectomized partner, 2 barrier methods, or 1 barrier method with spermicide)
* Willingness and ability to comply with study procedures for the duration of the study.
* To be eligible for treatment with investigational medicinal product (IMP) in study 28851, the subjects must not meet any of the following criteria:
* Non-eligibility for participation in extension study 28851 (premature discontinuation of core study 28063).
* Major protocol violation or non-compliance in the core study.
* Use of prohibited immunomodulatory / immunosuppressive therapies
* Serum immunoglobulin G (IgG) level \<3 gram per liter (g/L) if the subject received atacicept in the core study, or serum IgG level \<6 g/L if the subject received placebo in the core study (to protect the blinding of the core study, the IgG level will be communicated to the treating physician only if it is too low for extension study participation and only after all Week 36 assessments performed within the core study have been completed).
* Any condition, including laboratory findings that, in the opinion of the Investigator, constitutes a risk or a contraindication for participation in the extension study, or that could interfere with the study objectives, conduct or evaluation.
* Known active clinically significant acute or chronic infection, or any major episode of infection requiring hospitalization or treatment with parenteral anti-infectives.
* Investigator judgement that treatment of the subject with atacicept in the extension study is not appropriate.
* Aspartate aminotransferase (AST), or alanine aminotransferase (ALT), or alkaline phosphatase (AP) level greater than (\>)2.5 x upper limit of normal (ULN), or total bilirubin \>1.5 x ULN at eligibility assessment.
* Clinically significant abnormality in any hematological test (e.g. hemoglobin \<100 g/L (6.21 millimoles per liter \[mmol/L\]), white blood cells \<3 x 10\^9 per liter (/L), platelets \<100 x 10\^9/L) at eligibility assessment.
* Clinically significant abnormality on electrocardiogram (ECG) performed at eligibility assessment.
* Presence of uncontrolled or New York Health Association (NYHA) class 3 or 4 congestive heart failure at Week 36 of the core study.
* Moderate to severe renal impairment (creatinine clearance \<50 milliliter per minute (mL/min) according to Cockcroft-Gault equation).
* Allergy or hypersensitivity to gadolinium (Gd).
* Allergy or hypersensitivity to atacicept or to any of the components of the formulated atacicept.
* Diagnosis or family history of Creutzfeldt-Jakob disease (CJD).
C: Key Inclusion Criteria:

* Multiple Sclerosis (MS) subjects who have a confirmed diagnosis of relapsing-remitting MS according to McDonald criteria #1-4 and a baseline Expanded Disability Status Scale (EDSS) between 0.0 and 5.0, inclusive, who meet either of the following 2 criteria:

  * Have experienced at least 1 relapse within the 12 months prior to randomization, with a cranial magnetic resonance imaging (MRI) demonstrating lesion(s) consistent with MS , OR
  * Show evidence of gadolinium-enhancing lesions of the brain on an MRI performed within the 6 weeks prior to randomization.

Key Exclusion Criteria:

* Diagnosis of primary progressive, secondary progressive, or progressive relapsing MS
* History of malignancy
* History of severe allergic or anaphylactic reactions or known drug hypersensitivity
* History of abnormal laboratory results based on investigator judgment
* History of human immunodeficiency virus (HIV) or other immunodeficient conditions
* History of drug or alcohol abuse within the 2 years prior to randomization
* An MS relapse that has occurred within the 50 days prior to randomization AND/OR the subject has not stabilized from a previous relapse prior to randomization
* Positive screening for active infection with Hepatitis B virus or Hepatitis C virus
* Varicella or herpes zoster virus infection or any severe viral infection within 6 weeks before Screening
* Exposure to varicella zoster virus within 21 days before Screening.
* Abnormal blood tests at Screening: Hemoglobin ≤9.0 g/dL, Platelets ≤100 × 10\^9/L, Lymphocytes ≤1.0 × 10\^9/L, Neutrophils ≤1.5 × 10\^9/L, alanine aminotransferase/serum glutamate pyruvate transaminase (ALT/SGPT), aspartate aminotransferase/serum glutamic oxaloacetic transaminase (AST/SGOT), or gamma-glutamyl-transferase \>2 times the upper limit of normal (ULN) and serum creatinine \>ULN.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
D: 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).

Answer: D