None listed
Conditions
Brief summary
A phase III randomised, double-blind, placebo-controlled, multicentre study to evaluate the efficacy and safety of treatment with corticoSTeroids at onset, And Rituximab during a relapse, of Myelin Oligodendrocyte Glycoprotein antibody-associated disease. Ultimately, the STAR-MOG trial will identify if two cost-effective and globally available immunotherapies can reduce relapse rates and improve outcomes of people with MOGAD, with national and global implications for clinical care.
Interventions
Onset arm: To evaluate the efficacy of an optimised corticosteroid tapering regime at the onset of Myelin Oligodendrocyte Glycoprotein antibody-associated disease (MOGAD) in delaying time to first centrally adjudicated relapse compared to placebo. Dose: 4 months of tapered oral prednisone or placebo administered.
Adults and paediatric patients >40kg: All patients – Week -2 and -1 up till randomisation – 3 to 5 days of IV methylprednisolone or high dose oral prednisone, followed by oral prednis
Onset arm: To evaluate the efficacy of an optimised corticosteroid tapering regime at the onset of Myelin Oligodendrocyte Glycoprotein antibody-associated disease (MOGAD) in delaying time to first centrally adjudicated relapse compared to placebo. Dose: 4 months of tapered oral prednisone or placebo administered. Adults and paediatric patients >40kg: All patients – Week -2 and -1 up till randomisation – 3 to 5 days of IV methylprednisolone or high dose oral prednisone, followed by oral prednisone >20 mg/day till randomisation (Week 0). Active treatment arm: Active oral prednisone Weeks 1 and 2: 20mg per day, Weeks 3 and 4: 15mg per day, Weeks 5-10 12.5mg per day, Week 11: 10mg per day, Week 12: 7.5mg per day, Week 13: 5mg per day, Week 14: 2.5mg per day, then cease. Placebo arm: Week 1: 10mg active oral prednisone per day, Week 2: 5 mg active oral prednisone per day, Weeks 3-14 matched oral placebo, then cease. Paediatric patients 20-39 kg: All patients – Week -2 and -1 up till randomisation – 3 to 5 days of IV methylprednisolone or high dose oral prednisone, followed by oral prednisone >15 mg/day till randomisation (Week 0). Active treatment arm: Weeks 1 to 4: active oral prednisone 12.5mg per day, Weeks 5 to 10: 10mg per day, Week 11: 7.5mg per day, Week 12: 5mg per day, Week 13: 5mg per day, Week 14: 2.5mg per day. Placebo arm: Weeks 1 and 2: 2.5mg active oral prednisone per day, Weeks 3-14 matched oral placebo, then cease. Paediatric patients <20kg: All patients – Week -2 and -1 up till randomisation – 3 to 5 days of IV methylprednisolone or high dose oral prednisone, followed by oral prednisone >10 mg/day till randomisation (Week 0). Active treatment arm: Weeks 1 to 4: 10mg per day, Weeks 5 to 10: 7.5mg per day, Weeks 11 and 12: 5mg per day, Weeks 13 and 14: 2.5mg per day, then cease. Placebo arm: Weeks 1 and 2: 2.5mg active oral prednisone per day, Weeks 3-14 matched oral placebo, then cease. Adherence will be monitored by tablet returns and a participant diary. Relapsing arm: To evaluate the efficacy of 12 months of B cell depletion with rituximab infusion following a relapse of MOGAD in delaying time to first centrally adjudicated relapse compared to placebo. Adults and paediatric patients >40kgs; 1000mg rituximab infusions at Week 0, Week 2 and at 6 months. Paediatric patients 25-40kgs, 750mg rituximab infusions at Week 0 and Week 2, and two x 750mg infusions over a 2 week interval at month 6. Paediatric patients <25kgs, 500mg rituximab infusions at Week 0 and Week 2, and two x 500mg infusions over a 2 week interval at month 6. Adherence will be monitored by attendance to infusion visits.
Sponsors
University of Sydney
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Healthy volunteers
No
Inclusion criteria
Onset MOGAD Group: 1. All children and adults who meet 2023 International Diagnostic Criteria for MOGAD, with suspected clinical phenotypes for MOGAD (optic neuritis, transverse myelitis, acute disseminated encephalomyelitis, brainstem/cerebellar demyelination, cortical encephalitis, cerebral monofocal or polyfocal deficits with demyelination) and serum MOG antibody clear positive by cell-based assay and exclusion of alternate diagnosis. If low positive or tested without titre provided or CSF restricted MOG antibody positive, then this patient is required to fulfill additionally required clinical and/or radiological supportive criteria as per International Diagnostic Criteria. 2. Willingness to provide informed consent and participate and comply with study requirements 3. Available to attend clinic visits within one month of each time point on the schedule of assessments. Relapsing MOGAD Group: 1. All children and adults who meet 2023 International Diagnostic Criteria for MOGAD, with suspected clinical phenotypes for MOGAD (optic neuritis, transverse myelitis, acute disseminated encephalomyelitis, brainstem/cerebellar demyelination, cortical encephalitis, cerebral monofocal or polyfocal deficits with demyelination), and MOG antibody seropositive by cell-based assay in the last 12 months before their relapse, and exclusion of alternate diagnosis. 2. A relapse within 12 months of recruitment into this trial. A relapse is defined by the occurrence of new or worsening, acute neurological symptom(s) with objective changes (clinical findings or signs) on clinical (neurological and ophthalmological) examination that persists for more than 24 hours as confirmed by the investigator, separated by a period of neurological recovery/stability from any prior disease activity by at least one month. The symptoms must be attributable to MOGAD, with other potential causes (such as infection, injury, changes in mood, adverse reactions to medications, or other diagnoses) ruled out. 3. For women of childbearing potential: participants who agree to use adequate contraception during the treatment period and for at least six months after the final dose of IMP or placebo. 4. Willingness to provide informed consent and participate and comply with study requirements 5. Available to attend clinic visits within one month of each time point on the schedule of assessments.
Exclusion criteria
Onset MOGAD Group: 1. Presentation clinically and radiologically consistent with multiple sclerosis 2. A clinical presentation considered atypical for MOGAD 3. AQP4-IgG seropositive 4. Significant, active and/or untreated infection (inclusive but not limited to active hepatitis B, hepatitis C, HIV, tuberculosis, syphilis, strongyloides, etc). Patients with active infection will require treatment before they can fulfill inclusion criteria. 5. Patients who will be given additional immunotherapy apart from the Investigational Medicinal Product (IMP) or placebo after four weeks post initiation of high dose corticosteroids. 6. Women of child-bearing potential who are planning pregnancy in the next twelve months or are currently pregnant 7. Any concomitant autoimmune disease other than MOGAD that requires ongoing immunotherapy throughout the trial period 8. A significant comorbidity that in the opinion of the site’s principal investigator, would negatively affect MOGAD outcomes or preclude administration of corticosteroids 9. Circumstances/conditions which may interfere with the participant’s ability to give informed consent 10. Any routine screening test results which the site investigator feels places the patient at risk if they proceed with the trial 11. Known hypersensitivity or allergic reaction to IMP Relapsing MOGAD Group: 1. Presentation clinically and radiologically consistent with multiple sclerosis 2. A clinical presentation considered atypical for MOGAD 3. AQP4-IgG seropositive 4. Current B cell depletion as determined by B cell subsets at screening visit 5. Significant, active and/or untreated infection (inclusive but not limited to active hepatitis B, hepatitis C, HIV, tuberculosis, syphilis, strongyloides, etc). Patients with active infection will require treatment before they can fulfill inclusion criteria. 6. Women of child-bearing potential who are planning pregnancy in the next twelve months or are currently pregnant 7. Receipt of a live or live attenuated vaccine within six weeks prior to screening visit, or planned live or live attenuated vaccine during the study period 8. Any concomitant autoimmune disease other than MOGAD that requires ongoing immunotherapy throughout the trial period 9. A significant comorbidity that in the opinion of the site’s principal investigator, would negatively affect MOGAD outcomes or preclude administration of rituximab 10. Any routine screening test results which the site investigator feels places the patient at risk if they proceed with the trial 11. Circumstances/conditions which may interfere with the participant’s ability to give informed consent 12. Known hypersensitivity or allergic reaction to the IMP Exclusion criteria related to previous or concomitant immunotherapy for MOGAD B cell depletion in the six months prior to screening Cycophosphamide in the twelve months prior to screening IL-6R antagonists such as satralizumab or tocilizumab in the six weeks prior to screening (including participation in the Roche Meteoroid study – satralizumab vs placebo) Tacrolimus or cyclosporine in the six weeks prior to screening FcRn mAbs in the six weeks prior to screening (including participation in the UCB CosMOG study – rozanolixizumab vs placebo) Alemtuzumab in the 12 months prior to screening Planned ongoing treatment with MS disease modifying therapy (glatiramer acetate, interferon, fumarates, teriflunomide, natalizumab, fingolimod, siponimod, ozanimod, cladribine, alemtuzumab after the documented MOGAD relapse prompting consideration for this trial) Concurrent immunotherapy apart from IMP/placebo after four weeks post randomisation while in the double blind phase of the trial, until time of first relapse (or to the end of 12 months in patients without a relapse).
Outcome results
None listed