Efficacy and Safety Study of Satralizumab (SA237) as Monotherapy to Treat Participants With Neuromyelitis Optica (NMO) and Neuromyelitis Optica Spectrum Disorder (NMOSD)
Condition: Neuromyelitis Optica (NMO); NMO Spectrum Disorder (NMOSD)
MeSH terms: Neuromyelitis Optica
Intervention: Satralizumab; Placebo
Intervention description: Satralizumab will be administered subcutaneously (SC) at Weeks 0, 2, and 4, and thereafter once every 4 weeks (Q4W).; Placebo will be administered subcutaneously (SC) at Weeks 0, 2, and 4, and thereafter once every 4 weeks (Q4W).
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 95.0
Sex: All
Minimum age: 18 Years
Maximum age: 74 Years
Healthy volunteers: No

Summary:

      The objectives of this study are to evaluate the efficacy, safety, pharmacodynamic,
      pharmacokinetic and immunogenic profiles of satralizumab in participants with NMO and NMOSD.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Participants must be diagnosed as having either neuromyelitis optica (NMO) or NMO
             spectrum disorder (NMOSD), defined as the following:

               1. NMO as defined by Wingerchuk et al. 2006 criteria (requires all of the following
                  3 criteria: I. Optic neuritis, II. Acute myelitis, III. At least two of three
                  supportive criteria: Contiguous spinal cord lesion identified on a magnetic
                  resonance imaging [MRI] scan extending over 3 vertebral segments; Brain MRI not
                  meeting diagnostic criteria for multiple sclerosis [MS]; NMO-IgG seropositive
                  status)

               2. NMOSD as defined by either of following criteria with anti-aquaporin-4 (AQP4)
                  antibody seropositive status at screening: i. Idiopathic single or recurrent
                  events of longitudinally extensive myelitis (≥3 vertebral segment spinal cord MRI
                  lesion); ii. Optic neuritis, single, recurrent or simultaneous bilateral

          2. Clinical evidence of at least 1 documented relapse (including first attack) in last 12
             months prior to screening

          3. Expanded Disability Status Scale (EDSS) score from 0 to 6.5 inclusive at screening

          4. Age 18 to 74 years, inclusive at the time of informed consent

          5. Ability and willingness to provide written informed consent and to comply with the
             requirements of the protocol

        Exclusion Criteria:

          1. Clinical relapse onset (including first attack) within 30 days prior to baseline

             Exclusion Criteria Related to Previous or Concomitant Therapy:

          2. Any previous treatment with interleukin 6 (IL-6) inhibitory therapy (e.g.,
             tocilizumab), alemtuzumab, total body irradiation or bone marrow transplantation at
             any time

          3. Any previous treatment with anti-CD20, eculizumab, anti-BLyS monoclonal antibody
             (e.g., belimumab), any other treatment for prevention of multiple sclerosis (MS)
             relapse (e.g., interferon, natalizumab, glatiramer acetate, fingolimod, teriflunomide
             or dimethyl fumarate) within 6 months prior to baseline

          4. Any previous treatment with anti-CD4, cladribine, cyclophosphamide or mitoxantrone
             within 2 years prior to baseline

          5. Treatment with any investigational agent within 3 months prior to baseline

             Exclusions for General Safety:

          6. Pregnancy or lactation.

          7. For participants of reproductive potential, a positive result from a serum pregnancy
             test at screening, or not willing to use reliable means of contraception (physical
             barrier [participants or partner] in conjunction with a spermicidal product,
             contraceptive pill, patch, injectables, intrauterine device or intrauterine system)
             during the treatment period and for at least 3 months after the last dose of study
             drug

          8. Any surgical procedure (except for minor surgeries) within 4 weeks prior to baseline

          9. Evidence of other demyelinating disease or progressive multifocal leukoencephalopathy
             (PML)

         10. Evidence of serious uncontrolled concomitant diseases that may preclude participant
             participation, as described; Other nervous system disease, cardiovascular disease,
             hematologic/hematopoiesis disease, respiratory disease, muscular disease, endocrine
             disease, renal/urologic disease, digestive system disease, congenital or acquired
             severe immunodeficiency

         11. Known active infection (excluding fungal infections of nail beds or caries dentium)
             within 4 weeks prior to baseline

         12. Evidence of chronic active hepatitis B or C

         13. History of drug or alcohol abuse within 1 year prior to baseline

         14. History of diverticulitis that, in the Investigator's opinion, may lead to increased
             risk of complications such as lower gastrointestinal perforation

         15. Evidence of active tuberculosis (excluding participants receiving chemoprophylaxis for
             latent tuberculosis infection)

         16. Evidence of active interstitial lung disease

         17. Receipt of any live or live attenuated vaccine within 6 weeks prior to baseline

         18. History of malignancy within the last 5 years, including solid tumors, hematologic
             malignancies and in situ carcinoma (except basal cell and squamous cell carcinomas of
             the skin, or in situ carcinoma of the cervix uteri that have been completely excised
             and cured)

         19. History of severe allergic reaction to a biologic agent (e.g., shock, anaphylactic
             reactions)

         20. Active suicidal ideation within 6 months prior to screening, or history of suicide
             attempt within 3 years prior to screening

         21. History of Stevens-Johnson syndrome

         22. Following laboratory abnormalities at screening*.

               1. White blood cells <3.0 x10^3/microliter (μL)

               2. Absolute neutrophil count <2.0 x 10^3 /μL

               3. Absolute lymphocyte count <0.5 x 10^3 /μL

               4. Platelet count <10 x 10^4 /μL

               5. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >1.5 times the
                  upper limit of normal.

                    -  If retest is conducted, the last value of retest before randomization must
                       meet study criteria.