Study of Ublituximab in Early, Active, Autoantibody-Positive, IMMune-MedIated NecroTizing Myopathy (AIM01)
This is a multi-center, Phase 2 trial of ublituximab as first-line combination therapy in early, active autoantibody positive immune-mediated necrotizing myopathy. The primary objective is to estimate the effect of ublituximab as first add-on combination therapy at 24 weeks compared to placebo in treating early, active autoantibody positive immune-mediated necrotizing myopathy using the validated 2016 American College of Rheumatology/ European League Against Rheumatism (ACR/EULAR) Myositis Response Criteria, as measured by the Total Improvement Score (TIS)
• Participant must be able to understand and provide informed consent.
• Age 18 years or older at disease onset.
• Definite or probable IIM per the 2017 EULAR/ACR classification criteria.
• Diagnosis of IMNM, meeting the 2016 ENMC classification criteria and having either of the following antibodies:
‣ Anti-SRP
⁃ Anti-HMGCR
• Early disease as defined as onset of objective muscle weakness assessed by a physician and/or CK elevation attributed to IMNM within 1 year of the time of informed consent.
• Muscle weakness as assessed by an MMT-8 score \< 142 of 150 and CK \> 1.5x ULN along with abnormality in at least 1 of the following 4 CSMs at screening:
‣ PhGA ≥ 2 cm
⁃ PtGA ≥ 2 cm
⁃ Extramuscular global assessment ≥ 2 cm
⁃ HAQ-DI ≥ 0.25
• Treatment with only one of the following background immunosuppressant medications for IMNM for at least 12 weeks prior to randomization and the same dose for at least 4 weeks prior to randomization:
‣ Methotrexate up to 25 mg weekly
⁃ Mycophenolate mofetil up to 3000 mg daily
⁃ Mycophenolic acid up to 2160 mg daily
⁃ Azathioprine up to 2.5 mg/kg daily
⁃ Tacrolimus up to 0.2 mg/kg daily
⁃ Cyclosporine up to 5 mg/kg daily
• Current therapy consisting of glucocorticoid ≤ 20 mg/day of prednisone. The dose must be stable for at least 4 weeks prior to randomization. Participants who stopped treatment with glucocorticoids are eligible if the last dose of the glucocorticoids was at least 4 weeks before the time of informed consent.
• Female participants of childbearing potential and male participants with a partner of childbearing potential must agree to consistently and correctly use FDA approved highly effective methods of birth control, as shown in Appendix 1: Acceptable Contraception Methods for Females of Reproductive Potential, for the entire duration of the study and 6 months after last study drug infusion. Female participants of reproductive potential must have a negative pregnancy test at screening and at baseline.