Safety and Efficacy of Tocilizumab in Patients With Myelin Oligodendrocyte Glycoprotein Antibody-associated Disease
- Conditions
- Myelin Oligodendrocyte Glycoprotein Antibody-associated Disease
- Interventions
- Registration Number
- NCT06452537
- Lead Sponsor
- Tianjin Medical University General Hospital
- Brief Summary
The purpose of the study is to evaluate the safety and efficacy of Tocilizumab in MOGAD.
- Detailed Description
Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a rare autoimmune disease of the central nervous system, which can cause optic neuritis, myelitis, brainstem encephalitis, or encephalitis. The specific autoantibody against myelin oligodendrocyte glycoprotein antibody (MOG-IgG) has been indicated to contribute to the pathogenesis of the disease. Data from several cohorts suggests that around 50% of adult patients with MOG-IgG may relapse within the first two years of the disease, with most of relapses occurring early after disease onset. Few randomized controlled trials have ever been performed and therapeutic guidelines for this disease remain unclear especially after a single event. There is no drug approved for MOGAD by FDA. IL-6 is a pro-inflammatory cytokine which can promotes B cell activation, blood-brain barrier dysfunction, leukocyte migration, and the production of autoantibodies. Tocilizumab (ACTEMRA®), a humanized monoclonal antibody against the IL-6 receptor, has shown beneficial clinical effects and reduction of the risk of relapses in some patients with MOGAD. However, the efficacy of tocilizumab in MOGAD warrants further clinical trials.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 102
- Participants who are aged ≥12 years at the time of signing Informed Consent Form
- Confirmed diagnosis of MOGAD with a history of ≥1 MOGAD relapse in the 12 months prior to screening or ≥2 attacks in the 24 months prior to screening
- Anti-MOG antibody seropositive
- For women of childbearing potential: participants who agree to remain abstinent or use adequate contraception during the treatment period and for at least 3 months after the final dose of tocilizumab
- Patients must give written informed consent
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Any concomitant disease other than MOGAD that may require treatment with oral immunosuppressants or prednisone at doses >20 mg/day (or equivalent)
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Receipt of the following at any time prior to randomization Alemtuzumab Total lymphoid irradiation Bone marrow transplant T-cell vaccination therapy Receipt of rituximab or any experimental B-cell depleting agent within 6 months prior screening and B-cells below the lower limit of normal.
Receipt of intravenous immunoglobulin (IVIG) or plasma exchange (PE) within 1 month prior to randomization.
Receipt of any of the following within 3 months prior to randomization:
Natalizumab (Tysabri®). Methotrexate Mitoxantrone Cyclophosphamide Eculizumab
Receipt of any of the following within 6 weeks prior to randomization:
Tacrolimus Cyclosporin Mycophenolate mofetil
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Participants who are pregnant or breastfeeding, or intending to become pregnant during the study or within 3 months after the final dose of tocilizumab
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Participants with active or presence of recurrent bacterial, viral, fungal, mycobacterial infection, or other infection at baseline
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Participants with evidence of latent or active tuberculosis (excluding patients receiving chemoprophylaxis for latent tuberculosis infection)
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Participants with positive screening tests for hepatitis B and C
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Receipt of live or live attenuated vaccine within 6 weeks prior to baseline
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Known history of a severe allergy or reaction to any biologic therapy.
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History of alcohol, drug, or chemical abuse, or a recent history of such abuse < 1 year prior to randomization
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WBC < 3.0 × 10^3/mL, ANC < 2.0 × 10^3/mL, PLT < 10 × 10^4/mL, AST or ALT>1.5 ×ULN, Lymphocyte count < 0.5 × 10^3/mL
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Tocilizumab with oral prednisone Tocilizumab Tocilizumab will be intravenously administered as the dosage of 8 mg/kg every 4 weeks, with oral prednisone Prednisone Prednisone - Tocilizumab with oral prednisone Prednisone Tocilizumab will be intravenously administered as the dosage of 8 mg/kg every 4 weeks, with oral prednisone
- Primary Outcome Measures
Name Time Method Time from randomization to the first MOGAD relapse as determined by an adjudication committee Baseline, Up To 60 Weeks (End of Study) An adjudicated relapse was defined by the protocol and positively adjudicated by the relapse adjudication committee.
- Secondary Outcome Measures
Name Time Method Percentage of Participants With Worsening in Expanded Disability Severity Scale (EDSS) Score From Baseline to the end of study Baseline, Up To 60 Weeks (End of Study) Disease-related disability was measured by the EDSS. The EDSS was an ordinal clinical rating scale that ranges from 0 (normal neurologic examination) to 10 (death) in half-point increments. A decrease in score indicates improvement
Dosage of oral steroid at the end of the TOMATO trial Baseline, Up To 60 Weeks (End of Study) Dosage of oral steroid at the end of the TOMATO trial
Number of Participants With Adverse Events (AEs) Baseline, Up To 60 Weeks (End of Study) An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship
Sera MOG-IgG Concentration Over Time Baseline, Weeks 12, 24, 36, 48, 60 Weeks (End of Study) Sera MOG-IgG Concentration was measured by Cell-Based Assay (CBA)
Number of Participants With Adverse Events Serious Adverse Events (SAEs) Baseline, Up To 60 Weeks (End of Study) A SAE was any AE that resulted in death, life threatening, inpatient hospitalization or prolongation of existing hospitalization
Number of the lesion of the MRI T2WI Baseline, Weeks 12, 24, 36, 48, 60 Weeks (End of Study) Number of the lesion of the MRI T2WI
Trial Locations
- Locations (1)
Tianjin Medical University General Hospital
🇨🇳Tianjin, Tianjin, China