Neuromyelitis Optica (NMO), Neuromyelitis Optica Spectrum Disorders (NMOSD)
Conditions
Keywords
NMO, NMOSD, Inebilizumab, Glucocorticoids
Brief summary
Neuromyelitis optica spectrum disorder (NMOSD) is a central nervous system autoimmune condition mainly involving the spinal cord, optic nerves, and area postrema. The anti-aquaporin-4 (AQP4)-Immunoglobulin G (IgG) is a specific biomarker for NMOSD. Glucocorticoids(GCs) are used as first-line treatment for NMOSD. Oral glucocorticoids tapering is always suggested following the pused therapy in the maintenance phase. Inebilizumab, a humanized monoclonal antibody targeting CD19, has been proven effective in preventing NMOSD relapses. This study aims to evaluate and compare the efficacy and differences between glucocorticoids slow-tapering and rapid-tapering strategies combined with inebilizumab in preventing relapses in AQP4-IgG-seropositive NMOSD patients following an acute attack, with the goal of determining the optimal approach to steroid tapering and discontinuation after initiation of inebilizumab.
Interventions
DRUGSlow-tapering glucocorticoids + Inebilizumab
Slow-tapering glucocorticoids+Inebilizumab arm: A 300 mg intravenous infusion of inebilizumab will be administered on Day 1 and Day 15, followed by 300 mg infusions every 26 weeks thereafter. Prednisone will be initiated at a daily dose of 60 mg as concomitant therapy with inebilizumab. The prednisone dose will be tapered as follows: a reduction of 5 mg every 2 weeks until reaching 20 mg/day(Week 16); thereafter, a reduction of 5 mg every 4 weeks until discontinuation (a total duration of 32 weeks for combined inebilizumab and glucocorticoids therapy).
DRUGRapid-tapering glucocorticoids + Inebilizumab
Rapid-tapering glucocorticoids+Inebilizumab arm: A 300 mg intravenous infusion of inebilizumab will be administered on Day 1 and Day 15, followed by 300 mg infusions every 26 weeks thereafter. Prednisone will be initiated at a daily dose of 60 mg as concomitant therapy with inebilizumab, with a tapering schedule of 5 mg reduction per week until discontinuation (a total duration of 12 weeks for combined inebilizumab and glucocorticoids therapy).
Sponsors
Tianjin Medical University General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Ability and willingness to provide written informed consent and comply with the requirements of the study protocol. 2. Age ≥18 years, regardless of sex. 3. Diagnosis of NMOSD according to the 2015 International Panel for NMO Diagnosis (IPND) criteria. 4. Serum AQP4-IgG antibody positivity at screening. 5. An acute clinical attack (including the first attack) within 1 month before screening. After the acute attack was treated with high-dose corticosteroids, the current oral prednisone dose was reduced to 60 mg per day.
Exclusion criteria
1. Pregnant or breastfeeding women, or women planning to become pregnant during the study period. 2. Subjects with any serious acute, chronic, or recurrent infections (e.g., pneumonia, pyelonephritis, recurrent pneumonia, chronic bronchiectasis, tuberculosis, etc.). 3. Carriers of hepatitis B virus, or patients with chronic active hepatitis B or C, other chronic liver diseases, or HIV infection. 4. Abnormal liver function (ALT/AST \>2 times the upper limit of normal); moderate to severe renal impairment (glomerular filtration rate \<60 mL/min/1.73 m²). 5. Active malignancy. 6. Severe immunodeficiency. 7. Receipt of any B-cell depleting therapy within 6 months prior to initiation of baseline treatment, with B-cell counts below the lower limit of normal. 8. Receipt of other investigational treatments within 30 days prior to initiation of baseline treatment.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| First adjudicated relapse event within 54 weeks | Baseline, 54 Weeks |
Secondary
| Measure | Time frame |
|---|---|
| Change in serum Neurofilament Light chain (sNfL) levels at 54 weeks | Baseline, 54 Weeks |
| Change in serum Glial Fibrillary Acidic Protein (sGFAP) levels at 54 weeks | Baseline, 54 Weeks |
| Change in serum AQP4-IgG titer at 54 weeks | Baseline, 54 Weeks |
| Change in Expanded Disability Status Scale (EDSS) score from baseline at 54 weeks | Baseline, 54 Weeks |
| Change in Low-contrast Visual Acuity (LCVA) from baseline at 54 weeks | Baseline, 54 Weeks |
| Change in Timed 25-Foot Walk (T25-FW) test from baseline at 54 weeks | Baseline, 54 Weeks |
| Change in Expanded Disability Status Scale (EDSS) score from baseline at 106 weeks | Baseline, 106 Weeks |
| Change in Low-contrast Visual Acuity (LCVA) from baseline at 106 weeks | Baseline, 106 Weeks |
| Change in Timed 25-Foot Walk (T25-FW) test from baseline at 106 weeks | Baseline, 106 Weeks |
| Change in serum Neurofilament Light chain (sNfL) levels at 106 weeks | Baseline, 106 Weeks |
| Change in serum Glial Fibrillary Acidic Protein (sGFAP) levels at 106 weeks | Baseline, 106 Weeks |
| Change in serum AQP4-IgG titer at 106 weeks | Baseline, 106 Weeks |
| Change in Visual Analogue Scale (VAS) score from baseline at 54 weeks | Baseline, 54 Weeks |
| Change in Visual Analogue Scale (VAS) score from baseline at 106 weeks | Baseline, 106 Weeks |
| Immunoglobulin levels at 106 weeks | Baseline, 106 Weeks |
| Pelvic X-ray at 106 weeks | Baseline, 106 Weeks |
| Change in Quality of Life (QoL) score from baseline at 54 weeks | Baseline, 54 Weeks |
| Change in Quality of Life (QoL) score from baseline at 106 weeks | Baseline, 106 Weeks |
| Proportion of Relapse-free Participants at 54 weeks | Baseline, 54 Weeks |
| Proportion of Relapse-free Participants at 106 weeks | Baseline, 106 Weeks |
| Percentage of patients in glucocorticoid-free remission between 54 and 106 weeks | 54 Weeks, 106 Weeks |
| Annualized Relapse Rate (ARR) at 54 weeks | Baseline, 54 Weeks |
| Annualized Relapse Rate (ARR) at 106 weeks | Baseline, 106 Weeks |
| Daily and acumulate dose of glucocorticoids at relapse before 54 weeks | Baseline, 54 Weeks |
| Adverse events (AEs) and Serious AEs (SAEs) at 54 weeks | Baseline, 54 Weeks |
| Immunoglobulin levels at 54 weeks | Baseline, 54 Weeks |
| Pelvic X-ray at 54 weeks | Baseline, 54 Weeks |
| Adverse events (AEs) and Serious AEs (SAEs) at 106 weeks | Baseline, 106 Weeks |
Other
| Measure | Time frame |
|---|---|
| Lymphocyte Subpopulation Monitoring at 54 weeks | Baseline, 54 Weeks |
| Lymphocyte Subpopulation Monitoring at 106 weeks | Baseline, 106 Weeks |
Contacts
Primary ContactChun-Sheng Yang, M.D., Ph.D.
Outcome results
None listed