Clinical trial NCT06497374: FcRn Antagonists (Efgartigimod) for Acute NMOSD Attack
Official title: FcRn Antagonists (Efgartigimod) for Acute Neuromyelitis Optica Spectrum Disorders (NMOSD) Attack: a Phase 2, Randomized Controlled Trial.
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Neuromyelitis Optica
Neuromyelitis Optica Spectrum Disorder
NMO Spectrum Disorder
Lead sponsor: Tianjin Medical University General Hospital
Sponsor class: OTHER
First posted: 2024-07-11
Enrollment: 63
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: NMOSD is an autoimmune disease of the central nervous system that predominantly affects the spinal cord and optic nerves. The objectives of this study are to assess the efficacy and safety of FcRn antagonists (efgartigmod) for treatment of patients with neuromyelitis optica spectrum disorders during acute phase who are anti-aquaporin-4 (AQP4) antibody-positive. The potential of efgartigimod, an IgG1 Fc fragment that competes with IgG for FcRn binding, thereby lowering IgG levels, warrants further investigation as a treatment for acute neuromyelitis optica spectrum disorders attacks. This study aims to evaluate the therapeutic potential of efgartigmod in acute NMOSD attack.


Eligibility criteria: Inclusion Criteria:

1. Male or female, ages 18 to 75.
2. Meet the 2015 International Panel of Experts (IPND) diagnostic criteria for neuromyelitis optica spectrum disorders.
3. Acute EDSS nadir of 2.5-7.5, and a change of at least 0.5 points from baseline due to an acute relapse event.
4. Confirmation of serum AQP4-IgG antibody positivity using the CBA assay.
5. Confirmation of an acute attack of neuromyelitis optica spectrum disorders either with an acute optic neuritis and/or acute myelitis, defined as a worsening in the patient's signs and symptoms of neurological/visual impairment, an increase in the EDSS score, and symptoms lasting more than 24 hours and occurring more than 1 month since the last attack. Combination of imaging and clinical evaluation will be used to assess relapse and rule out a pseudorelapse.
6. New lesions or enhanced lesions need to be found in MRI.
7. Subjects who were receiving immunosuppressive therapy prior to the screening period will be required to agree to discontinue immunosuppression.
8. Treatment is stable at least 3 months.

Exclusion Criteria:

1. Other core clinical symptoms besides optic neuritis and myelitis.
2. Severe neuromyelitis optica spectrum disorder attack, which in the judgment of the investigator is not appropriate for this study. Severe is defined as requiring assisted ventilation or likely to require assisted ventilation during the study based on the judgment of the investigator.
3. Subjects with total IgG levels ≤ 6 g/L at screening.
4. Subjects with a B-cell count ≤ 5% of the lower limit of normal at screening.
5. Received high-dose intravenous methylprednisolone within 4 weeks prior to the screening period.
6. Received intravenous immunoglobulin, plasma exchange, or immunoadsorption treatment within 4 weeks prior to the screening period.
7. Received a vaccination within the first 4 weeks of the screening period or planned during the study.
8. Using of a monoclonal antibody or investigational drug not mentioned above that has immunomodulatory effects within 3 months or 5 half-lives (whichever is longer) prior to the screening period.
9. Subject is known to be allergic to any component of the study drug or any other FcRn drug or contrast medium for enhanced MRI.
10. Subject is known to have contraindications to taking methylprednisolone (for subjects in A and B group).
11. Subjects with clinically significant active infections (including unresolved or inadequately treated infections, including active tuberculosis) as assessed by the investigator.
12. Subjects with positive screening tests for hepatitis B and C who have received live or live attenuated vaccine within 6 weeks prior to baseline.
13. Subjects is known unable to taken MRI.
14. Subjects is known to have other ophthalmic disease that affect vision as assessed by the investigator.

Primary outcomes:
measure: Change in Neurological Disability - Expanded Disability Scale Score
timeFrame: Acute nadir to week4
Secondary outcomes:
measure: Change of FS score and MRC score at Week 12.
timeFrame: Baseline to week 12.
measure: Change of EDSS score, FS score, and MRC score at Week 4 and 24.
timeFrame: Baseline to Week 4 and Week 24.
measure: Change of EQ-5D-5L score.
timeFrame: Baseline to Week 4, 12 and 24.
measure: Change of high-contrast visual acuity in subjects with acute optic neuritis.
timeFrame: Baseline to Week 4, 12 and 24.
measure: Change of OCT measurements in subjects with acute optic neuritis.
timeFrame: Baseline to Week 4, 12 and 24.
measure: The proportion of participants requiring rescue treatment during the study period.
timeFrame: Baseline to Week 24.
measure: The incidence of adverse events in the subjects during the study period.
timeFrame: Baseline to Week 24.
measure: The vital signs, clinical laboratory indices, and electrocardiogram records of the subjects during the study period.
timeFrame: Baseline to Week 24.
Other outcomes:
measure: Change of serum total IgG levels.
timeFrame: Baseline to Week 4, 12 and 24.
measure: Change of serum AQP4-IgG antibody levels.
timeFrame: Baseline to Week 4, 12 and 24.
measure: Change of serum GFAP and NfL.
timeFrame: Baseline to Week 4, 12 and 24.
measure: Change of the size and extent of MRI lesions.
timeFrame: Baseline to Week 4, 12 and 24.
Locations:
Study officials:
References: