Phase 3 MOGwAI Trial to Test Azathioprine as First-Line Treatment for MOGAD

Author(s):

The randomized phase 3 trial will test the hypothesis that the initiation of azathioprine after a first attack of MOGAD could prevent further relapse and disability accrual.

Romain Marignier, MD, PhD

At the 40th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), held September 18-20 in Copenhagen, Denmark, investigators presented an overview of a new phase 3 study, dubbed MOGwAI (NCT05349006), that assesses the efficacy of azathioprine as a treatment option following first relapse in patients with myelin oligodendrocyte glycoprotein antibody associated disease (MOGAD). The multicenter study spanning across 14 institutions is expected to include 126 patients with 3 years, followed for a 36-month treatment period.¹

In the update, investigators noted that the first patients of the prospective study were randomly assigned to treatment in December 2023, with 6 others following after. To date, the main reasons for non-inclusion have been because of history with a prior relapse, low positive MOG-antibody titer, onset of symptoms later than 3 months, active infection, and active cancer. According to clinicaltrials.gov, the study is expected to complete in the first months of 2026.

Presented by lead investigator Romain Marignier, MD, PhD, a professor in the Neurological Hospital of Lyon, France, the study’s primary end point is the time to first relapse, comparing azathioprine vs placebo, during a randomized period of 3 years. Secondary end points of the study include safety, Expanded Disability Status Scale (EDSS) score and visual acuity worsening from baseline, and quality of life. Furthermore, the study also comprises exploratory end points that look at the dynamic of MRI and MOG-IgG titers.

MOGAD, a rare inflammatory disease, has been typically described as monophasic, with reports suggesting that around 50% of adult patients with MOG-IgG may relapse within the first 2 years of the disease. To date, no randomized controlled trial has been performed and therapeutic guidelines for this disease remain unclear after a single event. The hypothesis of MOGwAI is that the initiation of a treatment after a first attack of MOGAD should prevent further relapse and disability accrual.

In terms of eligibility, the study includes adults with the disease who had first attack of documented acute demyelinating syndrome of the central nervous system within the previous 3 months. Patients must test positive for MOG-antibodies, confirmed in a centralized lab. Those who are hypersensitive to azathioprine or steroids, have active infections or cancer, or with seriously impaired hepatic or bone marrow functions were excluded from the trial.

Azathioprine, an immunosuppressant, has been tested in patients with MOGAD in observational studies. At the 2021 Consortium of Multiple Sclerosis Centers (CMSC) Annual Meeting, a meta-analysis of such studies showed that azathioprine reduced annualized relapse rate (ARR) significantly in patients with MOGAD; however, more than one-third of the observed cohort continued to relapse.²

The meta-analysis featured 9 studies, comprising 127 patients with MOGAD. Overall, the standardized mean difference in pre- and post-treatment ARR was –0.828 (95% CI, –1.198 to –0.459; P <.001). In the study, investigators recorded greater SMD in the pediatric population (–0.911; 95% CI, –1.408 to –0.414; P <.001) than the adult population (SMD, –0.669; 95% CI, –1.230 to –0.019; P <.001). Notably, the relapse probability of MOGAD among children with azathioprine was 48.8% (95% CI, 31.4% to 66.4%; I2 <.001) while it was 50.9% (95% CI, 33.8% to 67.8%; I2 = 3.722) in an adult population. Furthermore, the change in Expanded Disability Status Scale scores was not significant with azathioprine treatment (SMD, –0.807; 95% CI, –1.078 to 0.464; P = .435).

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REFERENCES
1. Marignier R, Pique J, Banyahya L, et al. MOGwAI : A randomized double blind, placebo-controlled multicenter phase 3 trial to evaluate the efficacy of azathioprine for prevention of relapse in patients with myelin oligodendrocyte glycoprotein antibody associated disease after a first attack. Presented at: ECTRIMS Congress; September 18-20, 2024; ABSTRACT P1616/1250
2. Thakolwiboon S, Zhao-Fleming H, Karukote A, et al. The benefits of azathioprinte in myelin oligodendrocyte glycoprotein antibody associated disease: a systematic review and meta-analysis. Presented at: CMSC 2021. POSTER DMT64.