Ofatumumab in AQP4-IgG Seropositive NMOSD
- Registration Number
- NCT05504694
- Lead Sponsor
- Tang-Du Hospital
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 5
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Ofatumumab Ofatumumab The enrolled patients will receive ofatumumab (20 mg/0.4 ml) subcutaneously administered at baseline, Day 7, Day 14 and monthly thereafter. Patients will receive ofatumumab therapy for a total of 48 weeks.
- Primary Outcome Measures
Name Time Method Change from baseline in annual relapse rate (ARR) at last follow-up visit baseline, 12 months Pre-treatment ARR was determined at baseline by the total number of attacks divided by disease course from onset to baseline; post-treatment ARR is determined at 12 months after treatment by the number of relapses divided by 12 months.
- Secondary Outcome Measures
Name Time Method Change from baseline in Expanded Disability Status Scale (EDSS) score baseline, 3 months, 6 months, 9 months, 12 months Patients are followed up and EDSS score is determined. In general, the minimum and maximum scores of EDSS are 0 and 10, respectively, with higher scores meaning a worse outcome.
Change from baseline in lesion burden on MRI T2-weighted images baseline, 6 months, 12 months MRI is conducted to measure the lesion burden on T2-weighted images.
Change from baseline in immune landscape baseline, 1 week, 2 weeks, 1 month, 3 months, 6 months, 9 months, 12 months The dynamic changes of immune cells and cytokines are monitored, such as Th1 cells, Th2 cells, Th17 cells, NK cells, IL-1β, IL-2, IL-4, etc.
Adverse events 1 week, 2 weeks, 1 month, 3 months, 6 months, 9 months, 12 months Ofatumumab-related adverse events (AEs) are evaluated and the rate of AEs is recorded.
Change from baseline in optic coherence tomography (OCT) measures baseline, 6 months, 12 months OCT is done to measure peripapillary retinal nerve fiber layer (RNFL) thickness, macular ganglion cell-inner plexiform layer (GCIPL) thickness, and macular inner nuclear layer (INL) thickness.
Change from baseline in the frequencies of circulating B cell subsets baseline, 1 week, 2 weeks, 1 month, 3 months, 6 months, 9 months, 12 months Circulating B cell monitoring is conducted to evaluate the effectiveness of B-cell-depletion therapy. FACS is used to measure the frequencies of CD19+ B cells, CD19+CD27+ memory B cells, and CD19+CD38+CD27+ plasmablasts.
Biochemical indicators monitoring baseline, 1 month, 3 months, 6 months, 9 months, 12 months Blood routine test, liver and kidney function, immunoglobulins, complement, and serum AQP4-IgG titer.
Assessment of functional questionnaire baseline, 1 month, 3 months, 6 months, 9 months, 12 months SF-36, Functional Assessment of Chronic Illness Therapy (FACIT), EuroQol Health State (EQ-5D), Visual Analogue Pain Scale (VAPS), Timed 25-foot Walk Test, etc.
Trial Locations
- Locations (1)
Tangdu Hospital
🇨🇳Xi'an, Shaanxi, China
Tangdu Hospital🇨🇳Xi'an, Shaanxi, ChinaJun Guo, M.D.Principal InvestigatorYan Jia, M.S.Contact86-29-8471 7483neurologist_jiayan@163.com