Clinical trial NCT06452537: Safety and Efficacy of Tocilizumab in Patients With Myelin Oligodendrocyte Glycoprotein Antibody-associated Disease
Official title: A Randomized, Controlled, Multicenter Study To Evaluate the Safety and Efficacy of Tocilizumab In Patients With Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: Myelin Oligodendrocyte Glycoprotein Antibody-associated Disease
Lead sponsor: Tianjin Medical University General Hospital
Sponsor class: OTHER
First posted: 2024-06-11
Enrollment: 102
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Time from randomization to the first MOGAD relapse as determined by an adjudication committee
timeFrame: Baseline, Up To 60 Weeks (End of Study)
Secondary outcomes:
measure: Percentage of Participants With Worsening in Expanded Disability Severity Scale (EDSS) Score From Baseline to the end of study
timeFrame: Baseline, Up To 60 Weeks (End of Study)
measure: Dosage of oral steroid at the end of the TOMATO trial
timeFrame: Baseline, Up To 60 Weeks (End of Study)
measure: Sera MOG-IgG Concentration Over Time
timeFrame: Baseline, Weeks 12, 24, 36, 48, 60 Weeks (End of Study)
measure: Number of Participants With Adverse Events (AEs)
timeFrame: Baseline, Up To 60 Weeks (End of Study)
measure: Number of Participants With Adverse Events Serious Adverse Events (SAEs)
timeFrame: Baseline, Up To 60 Weeks (End of Study)
measure: Number of the lesion of the MRI T2WI
timeFrame: Baseline, Weeks 12, 24, 36, 48, 60 Weeks (End of Study)
Other outcomes:
Locations:
city: Tianjin
country: China
facility: Tianjin Medical University General Hospital
state: Tianjin
Study officials:
affiliation: Tianjin Medical University General Hospital
name: Chao Zhang, M.D., Ph.D
role: PRINCIPAL_INVESTIGATOR
References: