Clinical trial NCT05504694: Ofatumumab in AQP4-IgG Seropositive NMOSD
Official title: Efficacy and Safety of Ofatumumab in AQP4-IgG Seropositive NMOSD: an Open-label, Single-arm, Multicentre Prospective Pilot Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Neuromyelitis Optica Spectrum Disorder
Keywords: Neuromyelitis Optica Spectrum Disorder
Aquaporin 4
Ofatumumab
Lead sponsor: Tang-Du Hospital
Sponsor class: OTHER
Collaborators: name: Henan Provincial People's Hospital
First posted: 2022-08-17
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

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.

Primary outcomes:
measure: Change from baseline in annual relapse rate (ARR) at last follow-up visit
timeFrame: baseline, 12 months
Secondary outcomes:
measure: Change from baseline in Expanded Disability Status Scale (EDSS) score
timeFrame: baseline, 3 months, 6 months, 9 months, 12 months
measure: Change from baseline in lesion burden on MRI T2-weighted images
timeFrame: baseline, 6 months, 12 months
measure: Change from baseline in optic coherence tomography (OCT) measures
timeFrame: baseline, 6 months, 12 months
measure: Change from baseline in the frequencies of circulating B cell subsets
timeFrame: baseline, 1 week, 2 weeks, 1 month, 3 months, 6 months, 9 months, 12 months
measure: Change from baseline in immune landscape
timeFrame: baseline, 1 week, 2 weeks, 1 month, 3 months, 6 months, 9 months, 12 months
measure: Biochemical indicators monitoring
timeFrame: baseline, 1 month, 3 months, 6 months, 9 months, 12 months
measure: Assessment of functional questionnaire
timeFrame: baseline, 1 month, 3 months, 6 months, 9 months, 12 months
measure: Adverse events
timeFrame: 1 week, 2 weeks, 1 month, 3 months, 6 months, 9 months, 12 months
Other outcomes:
Locations:
city: Xi'an
country: China
facility: Tangdu Hospital
state: Shaanxi
Study officials:
affiliation: Tang-Du Hospital
name: Jun Guo, M.D.
role: PRINCIPAL_INVESTIGATOR
References: