Phase 2 Randomized Double‑Blind Placebo‑Controlled Trial of Subcutaneous Daxdilimab (with background prednisone) in Adults with Dermatomyositis or Anti‑Synthetase Myositis

The primary objective is to assess the efficacy of subcutaneous daxdilimab 300 mg compared with placebo in reducing overall disease activity at Week 24 in adults with inadequately controlled Dermatomyositis or anti‑synthetase inflammatory myositis, reflecting a clinically meaningful improvement in disease burden.

Secondary objectives include:

• Evaluation of the effect of daxdilimab versus placebo on disease activity at Week 24.
• Assessment of changes in cutaneous manifestations at Week 24.
• Determination of the reduction in concomitant corticosteroid dosage at Week 24.

The trial enrolled 70 adult participants, inclusive of both male and female subjects, aged 18 to 75 years, all diagnosed with either Dermatomyositis or anti‑synthetase inflammatory myositis according to the ACR/EULAR 2017 criteria. Eligibility required a definite or probable myositis classification based on a composite score (≥5.5 without biopsy or ≥6.7 with biopsy) and, for the DM cohort, the presence of a characteristic skin rash; for the ASIM cohort, positivity for anti‑Jo‑1 or related autoantibodies. Additional disease‑activity requirements included an MMT8 score below 142, at least two abnormal clinical muscle assessments, elevated muscle enzymes, and a HAQ‑DI score of ≥0.5. Participants were required to be on a stable regimen of standard‑of‑care therapy, including corticosteroids (≤20 mg prednisone equivalent daily) and up to two non‑excluded immunosuppressants for a minimum of four weeks, or to have undergone appropriate wash‑out periods if previously intolerant. The selection process emphasized stable health status aside from active myositis, with no specific dietary or physical‑activity restrictions beyond those dictated by disease management. The investigational agent daxdilimab was administered in a double‑blind, placebo‑controlled design to assess its effect on disease activity at Week 24.

The study is a Phase 2, randomized, double‑blind, placebo‑controlled trial evaluating the efficacy and safety of a single subcutaneous injection of 300 mg daxdilimab compared with a matching placebo in adult participants with inadequately controlled Dermatomyositis or anti‑synthetase inflammatory myositis. After an initial screening visit to confirm eligibility, participants are randomized on Day 1 and receive the study drug or placebo; background prednisone (≤20 mg/day) and up to two stable immunosuppressants may be continued. Follow‑up visits occur at regular intervals through Week 24 to assess the primary endpoint (Total Improvement Score) and secondary efficacy, pharmacokinetic, and safety measures. The end‑of‑study visit at Week 24 concludes the 24‑week participation period. Participants may be withdrawn early for predefined reasons, including significant treatment‑emergent adverse events, protocol non‑compliance, need for prohibited concomitant therapy, or voluntary discontinuation. The overall trial recruitment commenced in July 2023 and is planned to conclude by March 2026.

The investigational product Daxdilimab is supplied as a sterile injection for subcutaneous administration. Each dose contains 300 mg of the active monoclonal antibody in a single‑use vial. The medication is administered by a subcutaneous injection according to the study dosing schedule, with injections recorded in the investigational product log to verify timing and adherence.

The control arm receives a matched volume of placebo composed of 1 mL of a solution containing 20 mM L‑histidine/L‑histidine HCl, 240 mM sucrose, and 0.02 % (w/v) polysorbate 80, pH 6.0. The placebo is administered by the same subcutaneous route and schedule as the active agent to maintain blinding, and injection records are maintained similarly.

All participants continue background therapy with oral prednisone tablets at a dose of 20 mg per day. Various commercially available 20‑mg tablet formulations may be used, and the tablets are taken once daily. Concomitant prednisone use is documented in the medication diary, and compliance is assessed through pill counts and patient‑reported dosing logs at each study visit.

Efficacy will be evaluated using the Total Improvement Score (TIS) measured at Week 24 as the primary endpoint. The secondary efficacy assessments include the proportion of participants achieving a TIS increase of ≥40 or ≥20 without deterioration at two consecutive visits by Week 24, the change from baseline in the Cutaneous Dermatomyositis Disease Activity and Severity Index (CDASI) activity score, and the proportion of participants on an oral corticosteroid (OCS) dose ≥10 mg prednisone equivalent at baseline who attain a clinically meaningful reduction (≥25 % decrease or a dose ≤7.5 mg/day) by Week 24.

Pharmacokinetic and immunogenicity parameters will be collected to support efficacy interpretation: serum concentrations of daxdilimab will be measured over time, and the prevalence at baseline and incidence and titers of anti‑drug antibodies will be determined throughout the study. All laboratory assessments will be performed using validated analytical methods at predefined study visits.

Assessments will be conducted at baseline (Day 1) and at Week 24, with additional evaluations at the two consecutive visits required for the TIS proportion analyses. The TIS and CDASI scores will be obtained using the respective validated scoring instruments. OCS dose reductions will be documented based on recorded daily prednisone (or equivalent) dosages. Data will be analyzed according to the predefined statistical analysis plan, comparing daxdilimab with placebo for each efficacy parameter.