Ofatumumab in AQP4-IgG Seropositive NMOSD

Efficacy and Safety of Ofatumumab in AQP4-IgG Seropositive NMOSD: an Open-label, Single-arm, Multicentre Prospective Pilot Study

This is an open-label, single-arm, multicentre prospective pilot study to assess the efficacy and safety of ofatumumab in patients with AQP4-IgG seropositive neuromyelitis optica spectrum disorder (NMOSD) in China.

Neuromyelitis optica spectrum disorder (NMOSD) is a rare but severe demyelinating disorder that affects mainly adult patients. It is associated with a pathological B cell-mediated humoral immune response against the aquaporin-4 (AQP4) water channel. Monoclonal antibodies against CD20 have been shown to be effective for prevention of relapses in patients with NMOSD, and therefore been recommended as first-line therapy for this disorder. Ofatumumab (OFA), a fully humanized anti-CD20 monoclonal antibody, has been approved for multiple sclerosis treatment. However, prospective multicenter studies are needed to determine the efficacy and safety of ofatumumab in treating NMOSD.

Inclusion Criteria:

• Diagnosis of NMOSD according to the 2015 International Panel Diagnostic Criteria for NMOSD with AQP4-IgG.
• Clinical evidence of at least 2 relapses (including first attack) in past 24 months with at least 1 relapse occurring in the preceding 12 months.
• Adults aged ≥18 years old.
• Expanded disability status scale (EDSS) score between 0 and 7.5 (inclusive).
• Provision of written informed consent to participate in this study.
• Only oral corticosteroids were permitted at screening (≤10mg equivalent per day), which should be terminated within one month.
• Effective contraception was used for female patients with fertility during the treatment or at least 3 months after stopping medication.

Exclusion Criteria:

• Progressive neurological deterioration unrelated to relapses of NMOSD, or presence of neurological findings suspected with PML.
• Pregnant or breastfeeding patients and those with family planning during the study period.
• Patients participating in any other clinical therapeutic study at the screening or within 30 days of screening.
• Patients with splenectomy or history of no spleen, and those with planned surgery (excluding minor surgery) during the study period.
• Presence of uncontrolled severe concurrent diseases; long-term glucocorticoids or immunosuppressants use due to other autoimmune diseases, or presence of other chronic diseases that cannot receiving immunosuppression.
• Active infection at within 4 weeks before baseline.
• Positive for HBV or HCV.
• Evidence of latent or active tuberculosis (TB).
• Have received any live or live-attenuated vaccine within 6 weeks before baseline.
• History of malignancy in past 5 years, including solid tumor, malignant hematopathy and carcinoma in situ.
• History of severe allergic reactions to biological agents.
• Inability to provide written informed consent.