A Phase II Study Comparing Low- and High-Dose Alemtuzumab and High-Dose Rebif® in Patients With Early, Active Relapsing-Remitting Multiple Sclerosis
Condition: Multiple Sclerosis, Relapsing-Remitting
MeSH terms: Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Sclerosis
Intervention: Interferon beta-1a; Alemtuzumab 12 mg; Alemtuzumab 24 mg
Intervention description: Interferon beta-1a 44 microgram (mcg) subcutaneously 3-times weekly for 36 months.; Alemtuzumab 12 milligram per day (mg/day) was given by intravenous infusion on 5 consecutive days during the first month and on 3 consecutive days at months 12 and 24 (the latter at the treating physicians' discretion if the cluster of differentiation 4+ [CD4+] T-cell count was >=100*10^6 cells per liter).; Alemtuzumab 24 mg/day was given by intravenous infusion on 5 consecutive days during the first month and on 3 consecutive days at months 12 and 24 (the latter at the treating physicians' discretion if the CD4+ T-cell count was >=100*10^6 cells per liter).
Intervention MeSH terms: Interferons; Interferon-beta; Interferon beta-1a; Alemtuzumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Enrollment: 334.0
Sex: All
Minimum age: 18 Years
Maximum age: 50 Years
Healthy volunteers: No
Keywords: Multiple Sclerosis; Active Relapsing-Remitting Multiple Sclerosis

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.
    

Eligibility criteria:

        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