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

A Randomized, Controlled, Multicenter Study To Evaluate the Safety and Efficacy of Tocilizumab In Patients With Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD)

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

Study Overview

• Status: Active, not recruiting
• Conditions: Myelin Oligodendrocyte Glycoprotein Antibody-associated Disease
• Intervention / Treatment: Drug: Tocilizumab; Drug: Prednisone

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.

• Study Type: Interventional
• Enrollment (Estimated): 102
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100000
    • Chinese PLA General Hospital
  • Beijing, China, 100000
    • Beijing Tiantan Hospital, Capital Medical University
  • Beijing, China, 100000
    • China-Japan Friendship Hospital
  • Beijing, China, 100000
    • The First Affiliated Hospital of Tsinghua University
  • Beijing, China, 100000
    • Xuanwu Hospital Capital Medical University
  • Shanghai, China, 200000
    • Huashan Hospital, Fudan University
  • Tianjin, China, 300052
    • Tianjin Huanhu Hospital
  • Tianjin, China, 30052
    • Tianjin Children's Hospital
  • Anhui
    • Hefei, Anhui, China, 230001
      • Anhui Provincial Hospital
  • Gansu
    • Lanzhou, Gansu, China, 73000
      • The Second Hospital of Lanzhou University
  • Hebei
    • Shijiazhuang, Hebei, China, 050000
      • The Second Hospital of Hebei Medical University
    • Shijiazhuang, Hebei, China, 050000
      • Hebei Children's Hospital
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150086
      • The Second Affiliated Hospital of Harbin Medical University
  • Henan
    • Zhenzhou, Henan, China
      • The First Affiliated Hospital of Zhengzhou University
  • Inner Mongolia
    • Ordos, Inner Mongolia, China, 017000
      • Ordos Central Hospital
  • Jiangsu
    • Changzhou, Jiangsu, China, 213000
      • The Third Affiliated Hospital of Soochow University
    • Suzhou, Jiangsu, China, 215025
      • Children's Hospital of Soochow University
    • Xuzhou, Jiangsu, China, 221006
      • Affiliated Hospital of Xuzhou Medical University
  • Ningxia
    • Yinchuan, Ningxia, China, 751705
      • General Hospital of Ningxia Medical University
  • Shanxi
    • Taiyuan, Shanxi, China, 030000
      • First Hospital of Shanxi Medical University
  • Tianjin Municipality
    • Tianjin, Tianjin Municipality, China, 300052
      • Tianjin Medical University General Hospital
  • Xinjiang Uygur Autonomous Region
    • Ürümqi, Xinjiang Uygur Autonomous Region, China, 830001
      • People's Hospital of Xinjiang Uygur Autonomous Region

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Prednisone	Drug: Prednisone; Prednisone tapering protocol : If the starting dose is over 20mg/day, then reduce by one tablet weekly. Until the dose is reduced to 20mg/day then 20mg/day for two weeks→17.5mg/day for two weeks→12.5mg for four weeks→10mg for four weeks→7.5mg as a maintain dosage
Experimental: Tocilizumab with oral prednisone; Tocilizumab will be intravenously administered as the dosage of 8 mg/kg every 4 weeks, with oral prednisone	Drug: Tocilizumab; Tocilizumab will be intravenously administered as the dosage of 8 mg/kg every 4 weeks, with oral prednisone.; Other Names: ACTEMRA®; Drug: Prednisone; Prednisone tapering protocol : If the starting dose is over 20mg/day, then reduce by one tablet weekly. Until the dose is reduced to 20mg/day then 20mg/day for two weeks→17.5mg/day for two weeks→12.5mg for four weeks→10mg for four weeks→7.5mg as a maintain dosage

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time from randomization to the first MOGAD relapse as determined by an adjudication committee	An adjudicated relapse was defined by the protocol and positively adjudicated by the relapse adjudication committee.	Baseline, Up To 60 Weeks (End of Study)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Worsening in Expanded Disability Severity Scale (EDSS) Score From Baseline to the 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	Baseline, Up To 60 Weeks (End of Study)
Dosage of oral steroid at the end of the TOMATO trial	Dosage of oral steroid at the end of the TOMATO trial	Baseline, Up To 60 Weeks (End of Study)
Sera MOG-IgG Concentration Over Time	Sera MOG-IgG Concentration was measured by Cell-Based Assay (CBA)	Baseline, Weeks 12, 24, 36, 48, 60 Weeks (End of Study)
Number of Participants With Adverse Events (AEs)	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship	Baseline, Up To 60 Weeks (End of Study)
Number of Participants With Adverse Events Serious Adverse Events (SAEs)	A SAE was any AE that resulted in death, life threatening, inpatient hospitalization or prolongation of existing hospitalization	Baseline, Up To 60 Weeks (End of Study)
Number of the lesion of the MRI T2WI	Number of the lesion of the MRI T2WI	Baseline, Weeks 12, 24, 36, 48, 60 Weeks (End of Study)

Collaborators and Investigators

• Sponsor: Tianjin Medical University General Hospital
• Investigators: Principal Investigator: Chao Zhang, M.D., Ph.D, Tianjin Medical University General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 9, 2024
• Primary Completion (Estimated): January 1, 2026
• Study Completion (Estimated): July 1, 2026

Study Registration Dates

• First Submitted: June 5, 2024
• First Submitted That Met QC Criteria: June 10, 2024
• First Posted (Actual): June 11, 2024

Study Record Updates

• Last Update Posted (Actual): January 8, 2026
• Last Update Submitted That Met QC Criteria: January 7, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Autoimmune Diseases; Immune System Diseases; Autoimmune Diseases of the Nervous System; Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease; Polycyclic Compounds; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Pregnadienediols; Prednisone; tocilizumab
• Other Study ID Numbers: 2024035

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No