Efficacy and Safety Study of Satralizumab (SA237) as Add-on Therapy to Treat Participants With Neuromyelitis Optica (NMO) and NMO Spectrum Disorder (NMOSD)
Condition: Neuromyelitis Optica (NMO); NMO Spectrum Disorder (NMOSD)
MeSH terms: Neuromyelitis Optica
Intervention: Satralizumab; Placebo; Baseline Treatment
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).; As specified in the protocol, one of the following drugs at a stable dose is required as monotherapy for baseline treatment during the double-blind period: azathioprine (AZA); mycophenolate mofetil (MMF); or oral corticosteroids (CS). For participants aged 12 to 17 years at the time of informed consent, baseline treatment with AZA or MMF in combination with oral CS is also permitted. Change or termination of baseline treatment is only permitted during the open-label extension period.
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 85.0
Sex: All
Minimum age: 12 Years
Maximum age: 74 Years
Healthy volunteers: No

Summary:

      The objective of this study is to evaluate the efficacy, safety, pharmacodynamic,
      pharmacokinetic, and immunogenic profiles of satralizumab, compared with placebo, in addition
      to baseline immunosuppressive treatment in participants with NMO and NMOSD.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patients 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 the following Wingerchuk 2007 criteria with
                  anti-AQP4 antibody (Ab) seropositive status at screening (i. Idiopathic single or
                  recurrent events of longitudinally extensive myelitis [≥3 vertebral segment
                  spinal cord MRI lesion]; ii. Optic neuritis: recurrent or simultaneous
                  bilateral); For patients aged 12 to 17 years, a minimum of 4 patients should be
                  positive for anti-AQP4Ab status at screening

          2. Clinical evidence of at least 2 documented relapses (including first attack) in the
             last 2 years prior to screening, at least one of which has occurred in the 12 months
             prior to screening

          3. EDSS score from 0 to 6.5 inclusive at screening

          4. Age 12 to 74 years, inclusive at the time of informed consent

          5. One of the following baseline treatments must be at stable dose as a monotherapy for 8
             weeks prior to baseline: Azathioprine; Mycophenolate mofetil; Oral corticosteroids.
             For participants aged 12 to 17 years, either of the following baseline treatments for
             relapse prevention can be allowed: Azathioprine + oral corticosteroids; Mycophenolate
             mofetil + oral corticosteroids

          6. Ability and willingness to provide written informed consent and to comply with the
             requirements of the protocol

        For adolescents who may be enrolled after the end of the double-blind period, the inclusion
        criterion 2 is as follows (other criteria are same): Clinical evidence of at least 2
        documented relapses (including first attack) prior to screening.

        Exclusion Criteria:

        Exclusion criteria related to previous or concomitant therapy:

          1. Any previous treatment with IL-6 inhibitory therapy (e.g. tocilizumab), alemtuzumab,
             total body irradiation or bone marrow transplantation at any time

          2. Any previous treatment with anti-CD20, eculizumab, belimumab, interferon, natalizumab,
             glatiramer acetate, fingolimod, teriflunomide or dimethyl fumarate within 6 months
             prior to baseline

          3. Any previous treatment with anti-CD4, cladribine or mitoxantrone within 2 years prior
             to baseline

          4. Treatment with any investigational agent within 3 months prior to baseline

             Exclusions for general safety:

          5. Pregnancy or lactation

          6. For patients of reproductive potential, a positive result from a serum pregnancy test
             at screening, or not willing to use reliable means of contraception (physical barrier
             [patient 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

          7. Any surgical procedure (except for minor surgeries) within 4 weeks prior to baseline

          8. Evidence of other demyelinating disease or progressive multifocal leukoencephalopathy
             (PML)

          9. Evidence of serious uncontrolled concomitant diseases that may preclude patient
             participation, such as: 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

         10. Known active infection (excluding fungal infections of nail beds or caries dentium)
             within 4 weeks prior to baseline

         11. Evidence of chronic active hepatitis B or C

         12. History of drug or alcohol abuse within 1 year prior to baseline

         13. History of diverticulitis that, in the Investigator's opinion, may lead to increased
             risk of complications such as lower gastrointestinal perforation

         14. Evidence of active tuberculosis (TB; excluding patients receiving chemoprophylaxis for
             latent TB infection)

         15. Evidence of active interstitial lung disease

         16. Receipt of any live or live attenuated vaccine within 6 weeks prior to baseline

         17. 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)

         18. History of severe allergic reaction to a biologic agent (e.g. shock, anaphylactic
             reactions)

         19. Active suicidal ideation within 6 months prior to screening, or history of suicide
             attempt within 3 years prior to screening

         20. Following laboratory abnormalities at screening*.

               1. White blood cells (WBC) <3.0 x10^3/microliter (μL)

               2. Absolute neutrophil count (ANC) <2.0 x10^3/μL

               3. Absolute lymphocyte count <0.5 x10^3/μL

               4. Platelet count <10 x 10^4/μL

               5. Aspartate aminotransferase (AST) or alanine aminotranferase (ALT) >1.5 times the
                  upper limit of normal (ULN) * If retest is conducted, the last value of retest
                  before randomization must meet study criteria.

        For adolescents who may be enrolled after the end of the double-blind period, the
        annotation in the exclusion criterion 20 is as follows (other criteria are same): * If
        retest is conducted, the last value of retest before baseline must meet study criteria