Study of Subcutaneous Daclizumab in Patients With Active, Relapsing Forms of Multiple Sclerosis

• Pharmacokinetics
• Immunogenicity
• Clinical improvement

Inclusion Criteria:

• Male or female age 18 to 55 years, inclusive.
• Diagnosis of MS by McDonald criteria.
• EDSS <7.0.
• On stable IFN-beta regimen for at least 6 months.
• The occurrence of either of the following within 9 months prior to screening: ≥1 MS relapse OR A qualifying MRI, defined as an MRI that showed at least one confirmed Gd-CEL of the brain or spinal cord, was performed independently of the study while the patient was on a stable IFN-beta regimen, and is deemed acceptable by the central reader.
• For females, women of non-childbearing potential or women of childbearing potential who provide a negative serum pregnancy test at screen and within 24 hours of first dose of study drug, and who agree to use effective contraception during the Treatment and Follow-up periods of the study.
• Willing and able to comply with the protocol, provision of informed consent in accordance with institutional and regulatory guidelines, and, for US sites only, authorization to use protected health information.

Exclusion Criteria:

• Pregnant or breast-feeding woman.
• Non-ambulatory patient.
• Clinically significant abnormality on screening ECG.
• Malignancy within the past 5 years, except for adequately treated non-melanoma skin carcinoma or in situ carcinoma of the cervix.
• History of HIV infection, positive serology for HBV (hepatitis B virus) or HCV (hepatitis C virus).
• Varicella (VZV) or herpes zoster virus infection, or any severe viral infection, within 6 weeks before screening or exposure to VZV within 21 days of screening.
• Abnormal hematology, as defined by the following laboratory values: *Hemoglobin ≤8.5 g/dL, *Lymphocytes ≤1.0 x 10^9/L, *Platelets ≤100 x 10^9/L, *Neutrophils ≤1.5 x 10^9/L.
• Significant organ dysfunction, including but not limited to cardiac, renal, liver, non-MS related CNS, pulmonary, vascular, gastrointestinal, endocrine, or metabolic dysfunction, or other disease or condition, which in the opinion of the PI (principal investigator) would make the patient an unsuitable candidate for the study. Guidelines for levels of unacceptable dysfunction include: *creatinine ≥1.6 mg/dL; *AST and ALT ≥2.5 times upper limit of normal (ULN); *alkaline phosphatase ≥2.5 times ULN; *history of myocardial infarction, congestive heart failure, or arrhythmias within 6 months prior to randomization.
• Use of any of the following: *Any of the following types of live virus vaccine from 4 weeks before randomization: measles/mumps/rubella vaccine, varicella zoster virus vaccine, oral polio vaccine, and nasal influenza vaccine. Use of these vaccines, however, by household contacts does not affect the eligibility of patients to enroll or continue in the study; *Systemic corticosteroids, adrenocorticotropic hormone, or plasma exchange within 4 weeks before the baseline MRI scan (no more than 72 hours before Day 0); *Azathioprine, mycophenolate mofetil, methotrexate, glatiramer acetate, or intravenous immune globulin within 6 months before randomization; *An immunomodulatory agent within 6 months before randomization, except for interferon-beta products required per protocol; *An investigational agent within 6 months before randomization unless this agent is non-immunomodulatory and the medical monitor or steering committee rules that its use is acceptable on the theoretical basis of a lapse of at least 5 serum half-lives since administration of the last possible dose; *A monoclonal antibody (eg, Rituxan®/ Rituximab) within 6 months before randomization; *Daclizumab at any time prior to randomization; *Cladribine, mitoxantrone, cyclophosphamide, CamPath® (alemtuzumab), natalizumab (TYSABRI®/Antegren) or other drugs targeting alpha 4 integrin, total lymphoid irradiation, or bone marrow transplant at any time
• Patients for whom MRI is contraindicated, ie, have pacemakers or other contraindicated implanted metal devices, are allergic to gadolinium, or have claustrophobia that cannot be medically managed.
• Primary progressive MS.
• Clinically unstable for 30 days before randomization (Patients who experienced a relapse, with or without steroid treatment, during the screening period may be re-screened after 30 days.)
• Elective surgery performed from 2 weeks prior to randomization or scheduled through Week 44
• Infection (viral, fungal, bacterial) requiring hospitalization or IV antibiotics within 8 weeks before randomization.