Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase II, Randomized, Open-Label, Three-Arm Study Comparing Low- and High-Dose Alemtuzumab and High-Dose Subcutaneous Interferon Beta-1a (Rebif®) in Patients With Early, Active Relapsing-Remitting Multiple Sclerosis
Brief Summary: This was a Phase II, randomized, open-label, rater-blinded, three-arm study comparing two different doses of alemtuzumab (Lemtrada™) and one dose of subcutaneous (SC) interferon beta-1a (Rebif®) in participants with early, active relapsing-remitting multiple sclerosis (MS) who had not been previously treated with MS therapies other than steroids. The study was conducted for an initial period of 3 years and a follow-up to 5 years or more.


Options:
A: Key Inclusion Criteria:

* Must have a confirmed diagnosis of Relapsing Remitting Multiple Sclerosis (RRMS), and a cranial magnetic resonance imaging (MRI) demonstrating lesion(s) consistent with MS
* Must have a baseline Expanded Disability Status Scale (EDSS) between 0.0 and 5.0, inclusive
* Male subjects and female subjects of childbearing potential must be willing to practice effective contraception during the study and be willing and able to continue contraception for 4 months after their last dose of study treatment

Key Exclusion Criteria:

* Known intolerance, contraindication to, or history of non-compliance with Avonex® 30 µg
* History of treatment with Daclizumab High Yield Process (Dac HYP)
* History of malignancy
* History of severe allergic or anaphylactic reactions
* Known hypersensitivity to study drugs or their excipients
* History of abnormal laboratory results indicative of any significant disease
* History of human immunodeficiency virus (HIV) or other immunodeficient conditions
* History of drug or alcohol abuse (as defined by the Investigator) within the 2 years prior to randomization
* History of seizure disorder or unexplained blackouts OR history of a seizure within 6 months prior to Baseline
* History of suicidal ideation or an episode of clinically severe depression (as determined by the Investigator) within 3 months prior to Day 1
* 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
* Known history of, or positive screening test result for hepatitis C virus or hepatitis B 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

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

* Participants must have a confirmed and documented multiple sclerosis (MS) diagnosis as defined by the Revised McDonald criteria, with relapse onset disease or a relapsing-remitting disease course.
* Participants must be ambulatory with Kurtzke's expanded disability status scale (EDSS) score of 0 to 5.5 in both screening and randomization visits.
* Participants must be in a stable neurological condition, relapse-free and free of any corticosteroid treatment \[intravenous (IV), intramuscular (IM) and/or per os (PO)/oral\] or adrenocorticotrophic hormone, 60 days prior to randomization.
* Participants must have experienced at least one documented relapse in the 12 months prior to randomization.
* Participants must have disease duration of not more than 15 years.
* Women of child-bearing potential (for example, women who are not postmenopausal or surgically sterilized) must practice an acceptable method of birth control for 30 days before taking the study drug and two acceptable methods of birth control during the duration of the study and until 30 days after the last dose of study medication.

  * Additional criteria apply, please contact the investigator for more information.

Exclusion Criteria:

* Participants with progressive forms of MS.
* Participants with neuromyelitis optica.
* Use of experimental or investigational drugs and/or participation in drug clinical studies within the 6 months prior to randomization.
* Use of immunosuppressive agents or cytotoxic agents, including cyclophosphamide, within 6 months prior to randomization.
* Use of either of the following within 2 years prior to randomization visit: natalizumab (Tysabri®), rituximab, ocrelizumab, atacicept, belimumab, or ofatumumab.
* Use of teriflunomide (Aubagio®) within 2 years prior to randomization, except if active washout (with either cholestyramine or activated charcoal) was done 2 months or more prior to randomization.
* Previous treatment with glatiramer acetate (Copaxone®) Interferon β (either 1a or 1b), fingolimod (Gilenya®), dimethyl fumarate (Tecfidera®) or intravenous immunoglobulins within 2 months prior to randomization.
* Chronic (more than 30 consecutive days) systemic (IV, IM or PO) corticosteroid treatment within 2 months prior to randomization.
* Previous use of mitoxantrone (Novantrone®), cladribine, or alemtuzumab (Lemtrada®).
* Previous use of laquinimod.
* Previous total body irradiation or total lymphoid irradiation.
* Previous stem cell treatment, autologous bone marrow transplantation or allogenic bone marrow transplantation.
* Use of moderate/strong inhibitors of cytochrome P450 (CYP) 3A4 within 2 weeks prior to randomization.
* Use of inducers of CYP3A4 within 2 weeks prior to randomization visit.
* Pregnancy or breastfeeding.
* A known history of sensitivity to gadolinium (Gd).
* Inability to successfully undergo magnetic resonance imaging (MRI) scanning.
* Participants who underwent endovascular treatment for chronic cerebrospinal venous insufficiency within 3 months prior to randomization.

  * Additional criteria apply, please contact the investigator for more information.
C: Unless otherwise specified, to be eligible to participate in this study, candidates must meet the following eligibility criteria at the time of the randomization:

Key Inclusion Criteria:

* Must have confirmed diagnosis of RRMS according to McDonald criteria #1-4
* Must have a baseline EDSS between 0.0 and 5.0, inclusive.
* Must have relapsing-remitting disease course.

Key Exclusion Criteria:

* Other chronic disease of immune system, malignancies, urologic, pulmonary, gastrointestinal disease
* Pregnant or nursing women

Note: Other protocol-defined inclusion/exclusion criteria may apply.
D: Inclusion Criteria:

* Signed informed consent form (ICF)
* Male or non-pregnant, non-lactating female participants, 18 to 50 years of age (inclusive) as of signing the ICF
* Diagnosis of MS per McDonald's update of the Poser criteria, including cranial MRI consistent with those criteria (McDonald, 2001, Ann Neurol)
* Onset of first MS symptoms within 3 years prior to Screening as of signing the ICF
* Expanded Disability Status Scale (EDSS) score 0.0 to 3.0 (inclusive) at the screening and Baseline visits
* At least 2 completed clinical episodes of MS in the 2 years prior to study entry (that is, the initial event if within 2 years of study entry plus at least 1 relapse, or at least 2 relapses if the initial event was between 2 and 3 years prior to study entry)
* In addition to the clinical criteria, at least 1 enhancing lesion on any 1 of up to 4 screening gadolinium-enhanced MRI brain scans during a maximum 3-month run-in period (inclusive of the Month 0 Baseline scan)

Exclusion Criteria:

* Previous immunotherapy for MS other than steroids, including treatment with interferons, intravenous immunoglobulin (IVIG), glatiramer acetate, and mitoxantrone
* Personal history of thyroid autoimmune disease
* Personal history of clinically significant autoimmune disease (for example, inflammatory bowel disease, diabetes, lupus, severe asthma)
* History of thyroid carcinoma (previous thyroid adenoma was acceptable and was not considered an exclusion criterion)
* History of malignancy (except for basal cell skin carcinoma if disease-free for at least 5 years)
* Any disability acquired from trauma or another illness that, in the opinion of the Investigator, interfered with evaluation of disability due to MS
* Previous treatment with alemtuzumab
* History of anaphylaxis following exposure to humanized monoclonal antibodies
* Inability to undergo MRI with gadolinium administration
* Female participants of childbearing potential with a positive serum pregnancy test at screening or Baseline
* Male and female participants who did not agree to use effective contraceptive method(s) during the study
* Impaired renal function (that is, serum creatinine greater than or equal to 2 times the upper limit of normal \[ULN\])
* Untreated, major depressive disorder
* Epileptic seizures that were not adequately controlled by treatment
* Suicidal ideation
* Major systemic disease or other illness that, in the opinion of the Investigator, have compromised participant safety or interfered with the interpretation of study results
* Abnormal CD4 count or significantly abnormal thyroid function; presence of anti-thyroid stimulating hormone (TSH) receptor antibodies; known seropositivity for human immunodeficiency (HIV)
* Intolerance of pulsed corticosteroids, especially a history of steroid psychosis
* Presence of a monoclonal paraprotein
* Participants who had any form of MS other than relapsing-remitting
* Participants currently participating in a clinical study of an experimental or unapproved/unlicensed therapy

Answer: D