Therapy in the Acute Phase of NMOSD: A Multicenter Prospective Real-World Study

Official title

Eculizumab Add-On Therapy in the Acute Phase of Neuromyelitis Optica Spectrum Disorder: A Multicenter Prospective Real-World Study

Overview

This project is a multi-center, prospective, real-world cohort study that collects clinical data of Chinese patients with AQP4-positive NMOSD in the acute stage. It comprehensively assesses the clinical outcomes of the patients and aims to compare the clinical efficacy and safety of icoxib as a combined add-on treatment versus simple hormone shock therapy during the acute phase of NMOSD.Using simple hormone shock therapy (IVMP) as the control group, the efficacy and safety of etanercept treatment in the acute attack phase of Chinese patients with AQP4-positive neuromyelitis optica spectrum disorder (NMOSD) were evaluated.

Detailed description

Patients who met the inclusion and exclusion criteria were divided into three groups for their acute-phase treatment based on their treatment preferences:

1. Eculizumab plus treatment group: Eculizumab + IVMP (intravenous methylprednisolone pulse therapy) 2. Human immunoglobulin addition treatment group: IVIG + IVMP 3. Single IVMP treatment group: IVMP

Interventions

• Drug Eculizumab+IVMP
  (PETA-NMOSD Study): After the completion of intravenous methylprednisolone (IVMP), according to domestic treatment guidelines, it is necessary to continue immunosuppressive therapy and maintain it to prevent and reduce relapses. The specific treatment regimen is divided into four groups based on the patient's treatment preference.Eculizumab continuation treatment group,B-cell depletion treatment group,Mycophenolate mofetil group,Satellitezhuibao Treatment Group。
• Drug IVIG+IVMP
  Patients who met the inclusion and exclusion criteria were divided into three groups for their acute-phase treatment based on their treatment preferences: 1. Eculizumab plus treatment group: Eculizumab + IVMP (intravenous methylprednisolone pulse therapy) 2. Human immunoglobulin addition treatment group: IVIG + IVMP 3. Single IVMP treatment group: IVMP After completing the acute-phase treatment, patients who met the inclusion and exclusion criteria entered the conversion treatment study (PETA-
• Drug IVMP
  Single hormone shock therapy group: 1) Initiate hormone shock therapy during the acute phase of the attack (≤ 21 days); 2) Intravenous injection of methylprednisolone (IVMP) for 14 days: 1000 mg/day (5 days), 500 mg (3 days), 240 mg (3 days), 120 mg (3 days), then switch to oral administration.

Primary outcome measures

• Expanded Disability Status Scale score,EQ-5D-5L, [Time frame: baseline (before the acute attack and before the initiation of this treatment), and after hormone treatment at weeks 1, 2, 3, 4, 8 and 12]
• Expanded Disability Status Scale [Time frame: Baseline (before the acute attack treatment), after 1st, 2nd, 3rd, 4th week of hormone treatment, 8th and 12th week]

Eligibility criteria

Inclusion criteria

• Age: 18 - 65 years old, gender not restricted.
• Patients who meet the diagnostic criteria for NMOSD as set by the International Panel for NMO Diagnosis (IPND) in 2015, and have positive serum AQP4-IgG (by CBA method or live cell method).
• Acute phase of NMOSD-ON, defined as new or worsening optic nerve dysfunction (visual acuity decline accompanied or not by eye pain and visual field defect), with an onset duration of ≤ 21 days, and clear evidence of new or recurrent optic nerve damage on imaging (new or expanded T2WI lesions, with enhancement); the best corrected visual acuity (BCVA) of the affected eye during the acute phase of NMOSD-ON (if both eyes are affected simultaneously, the worse eye is considered) drops from above 0.3 to ≤ 0.1.
• Acute phase of NMOSD-TM, defined as new or worsening spinal cord dysfunction (limb weakness or numbness, accompanied or not by urinary and defecation disorders), with an onset duration of ≤ 21 days, and clear evidence of new or recurrent spinal cord damage on imaging (new or expanded T2WI lesions, with enhancement); the EDSS score during the acute phase of NMOSD-TM increases from ≤ 4.0 to ≥ 6.0.
• Clinical onset and recurrence determination requires unanimous judgment by each center and the center committee (an independent group of 3 people).
• Agree to receive meningococcal vaccine or use eculizumab during and 2 weeks after the medication.
• Sign the informed consent.

Exclusion criteria

• Damage to the optic nerve or spinal cord caused by other non-NMOSD-related factors.
• Abnormal laboratory indicators that need to be excluded from the subjects include, but are not limited to the following indicators:

Neutrophils < 1.5 × 109/L, Hemoglobin < 90g/L, Platelet count < 75 × 109/L; Serum creatinine > 1.5 × ULN, Total bilirubin > 1.5 × ULN, Aspartate aminotransferase (AST) > 1.5 × ULN, Alanine aminotransferase (ALT) > 1.5 × ULN, Alkaline phosphatase > 2 × ULN ； HbA1c > 8% (for diabetic patients); GFR < 60 mL/minute/1.73m2.

• Pregnant or lactating women, as well as those planning to become pregnant during the study period.
• Those who have received PE/IA/IVIG/FcRn/B-cell deletion/C5/IL-6 treatment within 1 month before enrollment.
• Active infections: active hepatitis B, hepatitis C, syphilis or HIV infection; active systemic infections or immunodeficiency diseases; unrelieved meningococcal infection of the meninges, or patients with severe infections that cannot use immunosuppressive drugs.
• Patients with severe internal or external diseases (not limited to such as heart failure, unstable angina pectoris, respiratory failure, pulmonary insufficiency, cachexia, organ transplantation, etc.).
• Those who have had or currently have an untreated malignant tumor that is not well controlled.
• Patients with serious physical or mental diseases that may affect the smooth implementation of the study.
• Patients known to be allergic to monoclonal drugs, murine proteins or any excipients.
• Patients who are intolerant to methylprednisolone or gamma globulin.
• Patients who cannot complete the magnetic resonance enhanced scan screening.
• Patients who are participating in other interventional clinical trials.
• Patients who cannot understand the questionnaire questions or cooperate with the questionnaire survey.
• Situations that the research team collectively deems unsuitable for participation in this study.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• the First Medical Center of Chinese PLA General Hospital — Beijing

Identifiers

NCT: NCT07410039 · bejing 301

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗