Ofatumumab for AQP4‑antibody positive neuromyelitis optica spectrum disorder

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

This pilot will try ofatumumab, a human anti‑CD20 antibody, in adults with AQP4‑IgG positive NMOSD who have had recent relapses to see if it reduces relapses and is safe.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 5 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Tang-Du Hospital (Academic / other)
• Drugs / interventions: ofatumumab
• Locations: 1 site (Xi'an, Shaanxi)
• Trial ID: NCT05504694 on ClinicalTrials.gov

What this trial studies

This is an open‑label, single‑arm, multicenter Phase 1/2 pilot trial in China testing ofatumumab in adults with AQP4‑IgG seropositive NMOSD who experienced at least two relapses in the past 24 months. Participants receive ofatumumab and are followed for clinical relapses, disability measured by EDSS, and safety outcomes. Key entry criteria include age ≥18, confirmed AQP4‑IgG positivity, EDSS 0–7.5, and limited concurrent oral corticosteroid use. The protocol builds on the effectiveness of anti‑CD20 therapy in NMOSD and onatumumab's approval for multiple sclerosis to gather prospective efficacy and safety data in this population.

Who should consider this trial

Good fit: Adults (≥18) with AQP4‑IgG seropositive NMOSD, EDSS 0–7.5, and at least two relapses in the past 24 months (including one in the past 12 months) who can attend the enrolling center and provide informed consent.

Not a fit: Patients who are AQP4‑IgG negative, have progressive non‑relapsing neurological decline, are pregnant or breastfeeding, or have contraindications to anti‑CD20 therapy are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, ofatumumab could reduce relapse frequency and improve disease control with a targeted B‑cell therapy that may offer a well‑tolerated option for AQP4‑IgG positive NMOSD.

How similar studies have performed: Other anti‑CD20 therapies such as rituximab and ocrelizumab have demonstrated benefit in preventing NMOSD relapses, but ofatumumab has limited prospective data in this specific condition.

Eligibility criteria

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.

Where this trial is running

Xi'an, Shaanxi

• Tangdu Hospital — Xi'an, Shaanxi, China (Recruiting)

Study contacts

• Principal investigator: Jun Guo, M.D. — Tang-Du Hospital
• Study coordinator: Jun Guo, M.D.

Conditions Neuromyelitis Optica Spectrum Disorder; Aquaporin 4; Ofatumumab