N-MOmentum: A Clinical Research Study of Inebilizumab in Neuromyelitis Optica Spectrum Disorders

A Double-masked, Placebo-controlled Study With Open-label Period to Evaluate the Efficacy and Safety of MEDI-551 in Adult Subjects With Neuromyelitis Optica and Neuromyelitis Optica Spectrum Disorders.

To compare the efficacy of inebilizumab (MEDI-551) versus placebo in reducing the risk of an neuromyelitis optica/neuromyelitis optica- spectrum disorders (NMO/NMOSD) attack in participants with NMO/NMOSD.

Inebilizumab is a genetically engineered humanized monoclonal antibody that binds to the B cell specific surface antigen cluster of differentiation (CD19) resulting in the depletion of B cells. Inebilizumab depletes antibody-secreting plasmablasts and some plasma cells, which are generally CD19 positive and CD20 negative.

The main objective of this study is to determine whether inebilizumab compare to placebo decreases the risk of an attack in participants with NMO/NMOSD.

This is a multicenter, multinational, randomized, double-masked, placebo controlled study with an open-label extension period to evaluate the efficacy and safety of intravenous (IV) inebilizumab in adult participants with NMO/NMOSD. After a screening period, eligible participants will enter a randomized-controlled period (RCP) of maximum 197 days where they will be randomized in a 3:1 ratio to receive either IV inebilizumab or placebo. NMO/NMOSD attacks will be evaluated by the investigator and confirmed against the attack criteria by an independent Adjudication Committee (AC). Participants for whom the attack was confirmed by the AC will be given the option to enroll into an open label period (OLP) with inebilizumab treatment. Participants who complete the RCP without experiencing an attack will be given the option to enroll into an OLP with inebilizumab treatment. The OLP will continue for a minimum of 1 year and a maximum of 3 years after the last participant enter the OLP. All participants who discontinue from the RCP or the OLP will continue in a Safety Follow-up for a total of 12 months from last dose to evaluate the long-term safety of the investigational product.

Inclusion Criteria:

1. Men and women 18 years or older with diagnosis of NMO/NMOSD

2. Confirmation of NMO/NMOSD status:

   1. AQP4-IgG sero-positive NMO/NMOSD with at least one attack requiring rescue therapy in the last year or two attacks requiring rescue therapy in the last 2 years
   2. AQP4-IgG sero-negative NMO with at least one attack requiring rescue therapy in the last year or two attacks requiring rescue therapy in the last 2 years

3. Able and willing to give written informed consent and comply with the requirements of the study protocol.

4. EDSS <= 7.5 (8 in special circumstances)

5. Men and women of reproductive potential must agree to use a highly effective method of birth control from screening to 6 months after final dose of the investigational product.

Exclusion Criteria:

1. Lactating and pregnant females

2. Treatment with any investigational agent within 4 weeks of screening

3. Known history of a severe allergy or reaction to any component of the investigational product formulation or history of anaphylaxis following any biologic therapy.

4. Known active severe bacterial, viral, or other infection or any major episode of infection requiring hospitalization.

5. History of alcohol, drug, or chemical abuse, or a recent history of such abuse < 1 year prior to randomization

6. Receipt of the following at any time prior to randomization:

   1. Alemtuzumab
   2. Total lymphoid irradiation
   3. Bone marrow transplant
   4. T-cell vaccination therapy

7. Receipt of rituximab or any experimental B-cell depleting agent within 6 months prior screening and B-cells below the lower limit of normal.

8. Receipt of intravenous immunoglobulin (IVIG) within 1 month prior to randomization.

9. Receipt of any of the following within 3 months prior to randomization:

   1. Natalizumab (Tysabri®).
   2. Cyclosporin
   3. Methotrexate
   4. Mitoxantrone
   5. Cyclophosphamide
   6. Tocilizumab
   7. Eculizumab

10. History of Hepatitis B and/or Hepatitis C (Hep B/C at screening)

11. Known history of a primary immunodeficiency (congenital or acquired) or an underlying condition such as human immunodeficiency virus (HIV) infection

12. History of malignancies, apart from squamous cell or basal cell carcinoma of the skin treated with documented success of curative therapy > 3 months prior to randomization

13. Any concomitant disease other than NMO/NMOSD that required treatment with oral or intravenous steroids at doses over 20 mg a day for over 21 days