ANZCTR - Registration

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Trial registered on ANZCTR

Registration number

ACTRN12624001258549p

Ethics application status

Submitted, not yet approved

Date submitted

18/09/2024

Date registered

16/10/2024

Date last updated

16/10/2024

Date data sharing statement initially provided

16/10/2024

Type of registration

Prospectively registered

Titles & IDs

Public title

STAR-MOG: 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.

Scientific title

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 in children and adults

Secondary ID [1]

Nil

Universal Trial Number (UTN)

U1111-1310-7631

Trial acronym

STAR-MOG

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Myelin Oligodendrocyte Glycoprotein antibody-associated disease

optic neuritis

transverse myelitis

Condition category

Condition code

Neurological

Other neurological disorders

Inflammatory and Immune System

Autoimmune diseases

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

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 Active treatment arm week 1 and 2: 20mg per day, week 3 and 4: 20mg per day, week 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. Placebo arm: week 1 and 2: 2.5mg active oral prednisone per day to them weeks 3-14 matched oral placebo.

Paediatric patients <20kg: week 1 to 4: 12.5mg per day, week 5 to 10: 10mg per day, week week 11: 7.5mg per day, week 12: 5mg per day, week 13: 5mg per day, week 14: 2.5mg per day. Placebo arm: week 1 and 2: 2.5mg active oral prednisone per day to them weeks 3-14 matched oral placebo.

Paediatric patients <20kg: week 1 to 4: 10mg per day, week 5 to 10: 7.5mg per day, week week 11 and 12: 5mg per day, week 13 and 14: 2.5mg per day. Placebo arm: week 1 and 2: 2.5mg active oral prednisone per day to them weeks 3-14 matched oral placebo.
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 infusion at week 0, week 2 and at 6 months. Paediatric patients <25kgs, 500mg infusion at week 0 and week 2 and 500mg at a 2 week interval at month 6. Paediatric patients 25-40kgs, 750mg infusion at week 0 and week 2 and 750mg infusion at a 2 week interval at month 6.
Adherence will be monitored by attendance to infusion visits.

Intervention code [1]

Treatment: Drugs

Comparator / control treatment

Onset arm: Oral vegetable-based microcellulose placebo tablet

Relapsing arm: Sterile intravenous saline solution 0.9%

Control group

Placebo

Outcomes

Primary outcome [1]

Relapse

Timepoint [1]

This will be measured if participants present to their treating clinician with any symptoms of a relapse for a follow-up period of 12 months following treatment initiation.

Secondary outcome [1]

Safety and tolerability; this will be assessed as a composite outcome

Timepoint [1]

Baseline, 2 months, 6 months, 12 months post intervention commencement

Secondary outcome [2]

Disease activity

Timepoint [2]

Baseline, 2 months, 6 months, 12 months post intervention commencement

Secondary outcome [3]

Neurological function

Timepoint [3]

Baseline, 2 months, 6 months, 12 months from intervention commencement

Secondary outcome [4]

Visual function

Timepoint [4]

Baseline, 6 months, 12 months from intervention commencement

Secondary outcome [5]

Patient Reported outcome measures (PROMS) - Anxiety and Depression. This will be assessed as a composite outcome as the combined scoring on the Hospital Anxiety and Depression Scale.

Timepoint [5]

Baseline, 6 months, 12 months from intervention commencement

Secondary outcome [6]

Disease activity

Timepoint [6]

Baseline, 2 months, 6 months, 12 months post intervention commencement

Secondary outcome [7]

Disease activity

Timepoint [7]

Baseline, 2 months, 6 months, 12 months post intervention commencement

Secondary outcome [8]

Neurological function

Timepoint [8]

Baseline, 2 months, 6 months, 12 months from intervention commencement

Secondary outcome [9]

Neurological function

Timepoint [9]

Baseline, 2 months, 6 months, 12 months from intervention commencement

Secondary outcome [10]

Neurological function

Timepoint [10]

Baseline, 2 months, 6 months, 12 months from intervention commencement

Secondary outcome [11]

Visual function

Timepoint [11]

Baseline, 2 months, 6 months, 12 months from intervention commencement

Secondary outcome [12]

Visual function

Timepoint [12]

Baseline, 2 months, 6 months, 12 months from intervention commencement

Secondary outcome [13]

Patient Reported outcome measures (PROMS) - Fatigue

Timepoint [13]

Baseline, 2 months, 6 months, 12 months from intervention commencement

Secondary outcome [14]

Patient Reported outcome measures (PROMS) - Quality of Life

Timepoint [14]

Baseline, 2 months, 6 months, 12 months from intervention commencement

Secondary outcome [15]

Patient Reported outcome measures (PROMS)- Fatigue

Timepoint [15]

Baseline, 2 months, 6 months, 12 months from intervention commencement

Secondary outcome [16]

Patient Reported outcome measures (PROMS) - Pain

Timepoint [16]

Baseline, 2 months, 6 months, 12 months from intervention commencement

Secondary outcome [17]

Patient Reported outcome measures (PROMS)- Visual function

Timepoint [17]

Baseline, 2 months, 6 months, 12 months from intervention commencement

Secondary outcome [18]

Patient Reported outcome measures (PROMS) - Bladder function

Timepoint [18]

Baseline, 2 months, 6 months, 12 months from intervention commencement

Secondary outcome [19]

Patient Reported outcome measures (PROMS)- bowel function

Timepoint [19]

Baseline, 2 months, 6 months, 12 months from intervention commencement

Secondary outcome [20]

Patient Reported outcome measures (PROMS) - Sexual function (adults only)

Timepoint [20]

Baseline, 2 months, 6 months, 12 months from intervention commencement

Secondary outcome [21]

Patient Reported outcome measures (PROMS) - Strengths and Difficulties (Paediatric only). This will be assessed as a composite outcome as a score resulting from the participant reported score.

Timepoint [21]

Baseline, 2 months, 6 months, 12 months from intervention commencement

Eligibility

Key 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.

Minimum age

No limit

Maximum age

No limit

Sex

Both males and females

Can healthy volunteers participate?

Key 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).

Study design

Purpose of the study

Treatment

Allocation to intervention

Randomised controlled trial

Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)

Contacting central unblinded administrator of allocation schedule

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Stratified randomisation based on:
1. Presence/absence of concurrent treatment (IVIg and/or PLEX up to four weeks after treatment initiation for Onset arm; or IVIg and/or PLEX prior to randomisation, and/or oral corticosteroids for first month post randomisation for Relapsing arm) AND
2. Disease phenotype (optic neuritis vs non optic neuritis)

Masking / blinding

Blinded (masking used)

Who is / are masked / blinded?

The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data

Intervention assignment

Parallel

Other design features

Phase

Phase 3

Type of endpoint/s

Safety/efficacy

Statistical methods / analysis

Categorical variables will be summarised using frequency and percentage and compared using a chi-square test or Fisher’s exact test as appropriate. Continuous variables will be summarised using mean, standard deviation (SD) and/or standard error (SE) and range; or median, inter-quartile range (IQR) and range compared using a t-test of Wilcoxon rank-sum test as appropriate. Time-to-event data will be visualised using Kaplan-Meier survival and/or failure curves. Cumulative incidence rates for count and event data will be presented as point estimates with associated 95% confidence intervals (95% CI) presuming an underlying Poisson, negative binomial or zero-inflated Poisson distribution as appropriate. All analyses, descriptive and inferential, will be performed for the onset and relapsing cohorts.

Recruitment

Recruitment status

Not yet recruiting

Date of first participant enrolment

Anticipated

3/02/2025

Actual

Date of last participant enrolment

Anticipated

5/02/2028

Actual

Date of last data collection

Anticipated

3/12/2029

Actual

Sample size

Target

228

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

NSW,QLD,SA,VIC

Funding & Sponsors

Funding source category [1]

Government body

Name [1]

Department of Health and Aged Care: MRFF

Address [1]

Country [1]

Australia

Primary sponsor type

University

Name

University of Sydney

Address

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Submitted, not yet approved

Ethics committee name [1]

Sydney Local Health District Ethics Review Committee (RPAH Zone)

Ethics committee address [1]

https://www.slhd.nsw.gov.au/rpa/research/

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

20/09/2024

Approval date [1]

Ethics approval number [1]

Summary

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.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

A/Prof Sudarshini Ramanathan

Address

Kids Neuroscience Centre, Kids Hospital at Westmead, 178A Hawkesbury Rd, Westmead NSW 2145

Country

Australia

Phone

+61 413314685

Fax

[email protected]

Contact person for public queries

Name

Isabella Cotter

Address

Kids Neuroscience Centre, Kids Hospital at Westmead, 178A Hawkesbury Rd, Westmead NSW 2145

Country

Australia

Phone

+61 405982588

Fax

[email protected]

Contact person for scientific queries

Name

Sudarshini Ramanathan

Address

Kids Neuroscience Centre, Kids Hospital at Westmead, 178A Hawkesbury Rd, Westmead NSW 2145

Country

Australia

Phone

+61 413314685

Fax

[email protected]

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

No/undecided IPD sharing reason/comment

Only analysed data will be publicly available.

What supporting documents are/will be available?

Doc. No.	Type	Email
24202	Study protocol	[email protected]
24203	Statistical analysis plan	[email protected]
24204	Informed consent form	[email protected]
24205	Ethical approval	[email protected]

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

No additional documents have been identified.

Trial Review

Documents added manually

Documents added automatically