Slow vs. Rapid Glucocorticoids Tapering With Inebilizumab in NMOSD (STARGlu-NMO)

The Efficacy of Slow - Tapering Versus Rapid - Tapering Glucocorticoid Strategies in Preventing Relapses of Neuromyelitis Optica Spectrum Disorder (NMOSD) When Combined With Inebilizumab: A Multicenter, Open - Label, Randomized Parallel - Controlled Clinical Trial

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Neuromyelitis Optica (NMO); Neuromyelitis Optica Spectrum Disorders (NMOSD)
• Intervention / Treatment: Drug: Slow-tapering glucocorticoids + Inebilizumab; Drug: Rapid-tapering glucocorticoids + Inebilizumab

• Study Type: Interventional
• Enrollment (Estimated): 170
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Chun-Sheng Yang, M.D., Ph.D.; Phone Number: +86-022-60814587; Email: cyang01@tmu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Slow-tapering glucocorticoids + Inebilizumab arm	Drug: Slow-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).
Active Comparator: Rapid-tapering glucocorticoids + Inebilizumab arm	Drug: Rapid-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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
First adjudicated relapse event within 54 weeks	Baseline, 54 Weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
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 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 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
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
Immunoglobulin levels at 106 weeks	Baseline, 106 Weeks
Pelvic X-ray at 106 weeks	Baseline, 106 Weeks

Other Outcome Measures

Outcome Measure	Time Frame
Lymphocyte Subpopulation Monitoring at 54 weeks	Baseline, 54 Weeks
Lymphocyte Subpopulation Monitoring at 106 weeks	Baseline, 106 Weeks

Collaborators and Investigators

• Sponsor: Tianjin Medical University General Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2025
• Primary Completion (Estimated): August 31, 2027
• Study Completion (Estimated): August 31, 2028

Study Registration Dates

• First Submitted: June 17, 2025
• First Submitted That Met QC Criteria: August 12, 2025
• First Posted (Actual): August 20, 2025

Study Record Updates

• Last Update Posted (Actual): August 20, 2025
• Last Update Submitted That Met QC Criteria: August 12, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: Glucocorticoids; NMO; Inebilizumab; NMOSD
• Additional Relevant MeSH Terms: Nervous System Diseases; Autoimmune Diseases; Immune System Diseases; Eye Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Myelitis, Transverse; Optic Neuritis; Optic Nerve Diseases; Cranial Nerve Diseases; Neuromyelitis Optica; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Glucocorticoids
• Other Study ID Numbers: YG20250610

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes