FcRn Antagonists (Efgartigimod) for Acute NMOSD Attack (FACT)

Tianjin Medical University

Status and phase: Not yet enrolling; Phase 2

Conditions: Neuromyelitis Optica; NMO Spectrum Disorder; Neuromyelitis Optica Spectrum Disorder

Treatments: Drug: High-dose intravenous methylprednisolone; Drug: Efgartigimod Alfa Injection

Study type: Interventional

Funder types: Other

Identifiers

NCT06497374

20240426

Details and patient eligibility

About

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.

Enrollment: 63 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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63 participants in 3 patient groups

Efgartigimod+IVMP group

Experimental group

Description:

Patients will receive efgartigimod alpha via intravenous infusion at a dose of 10 mg/kg, each infusion lasting approximately 2 hours, on Week 0, 1, 2 and 3. Efgartigimod should be administered no later than the second day after initiation of high-dose intravenous methylprednisolone therapy. This is delivered intravenously at a dosage of 1,000 mg/day for five consecutive days, which is then reduced to 500 mg/day for the next three days, followed by 240 mg/day for another three days, and then 120 mg/day for an additional three days. Subsequently, the treatment shifts to oral prednisone, starting with 60 mg daily for seven days, then decreasing to 50 mg daily for the next seven days, followed by 40 mg daily for another seven days. Afterward, the prednisone dosage is reduced by 5 mg every two weeks until it reaches 10 mg. After Week 4, Inebilizumab to prevent relapse will be introduced according to the indication.

Treatment:

Drug: Efgartigimod Alfa Injection

Drug: High-dose intravenous methylprednisolone

IVMP group

Experimental group

Description:

Patients will be treated with injectable methylprednisolone sodium succinate as described in Arm A. After Week 4, Inebilizumab to prevent relapse will be introduced according to the indication.

Treatment:

Drug: High-dose intravenous methylprednisolone

Efgartigimod group

Other group

Description:

Patients will be treated with efgartigimod alpha injection via intravenous infusion at a dosage of 10 mg/kg, with each session lasting approximately 2 hours, on Week 0, 1, 2 and 3. After Week 4, Inebilizumab to prevent relapse will be introduced according to the indication.

Treatment:

Drug: Efgartigimod Alfa Injection