Safety and Efficacy of Tocilizumab in Patients With Myelin Oligodendrocyte Glycoprotein Antibody-associated Disease (TOMATO)

Tianjin Medical University

Status and phase: Enrolling; Phase 3; Phase 2

Conditions: Myelin Oligodendrocyte Glycoprotein Antibody-associated Disease

Treatments: Drug: Prednisone; Drug: Tocilizumab

Study type: Interventional

Funder types: Other

Identifiers

NCT06452537

2024035

Details and patient eligibility

About

The purpose of the study is to evaluate the safety and efficacy of Tocilizumab in MOGAD.

Full 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.

Enrollment: 102 estimated patients

Sex: All

Ages: 12+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Participants who are aged ≥12 years at the time of signing Informed Consent Form
2. 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
3. Anti-MOG antibody seropositive
4. 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
5. Patients must give written informed consent

Exclusion criteria

1. Any concomitant disease other than MOGAD that may require treatment with oral immunosuppressants or prednisone at doses >20 mg/day (or equivalent)

2. 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

3. Participants who are pregnant or breastfeeding, or intending to become pregnant during the study or within 3 months after the final dose of tocilizumab

4. Participants with active or presence of recurrent bacterial, viral, fungal, mycobacterial infection, or other infection at baseline

5. Participants with evidence of latent or active tuberculosis (excluding patients receiving chemoprophylaxis for latent tuberculosis infection)

6. Participants with positive screening tests for hepatitis B and C

7. Receipt of live or live attenuated vaccine within 6 weeks prior to baseline

8. Known history of a severe allergy or reaction to any biologic therapy.

9. History of alcohol, drug, or chemical abuse, or a recent history of such abuse < 1 year prior to randomization

10. 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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102 participants in 2 patient groups

Tocilizumab with oral prednisone

Experimental group

Description:

Tocilizumab will be intravenously administered as the dosage of 8 mg/kg every 4 weeks, with oral prednisone

Treatment:

Drug: Prednisone

Drug: Tocilizumab

Prednisone

Experimental group

Treatment:

Drug: Prednisone