Trial Outcomes & Findings for A Phase 2 Proof of Concept Study to Evaluate the Efficacy and Safety of Daxdilimab in Participants With Dermatomyositis (DM) or Anti-synthetase Inflammatory Myositis (ASIM) (NCT NCT05669014)

A total of 12 participants with dermatomyositis (DM) or anti-synthetase inflammatory myositis (ASIM) were enrolled at 9 centers in Brazil, Czech Republic, Mexico, Spain, United Kingdom and United States between December 2023 and July 2025.

This trial consisted of Stage I-double-blind treatment period of up to 24 weeks and Stage II-open-label (OL) extension from Week 24 to Week 48. Due to enrollment feasibility challenges, protocol was amended in September 2024 to limit dosing to 20 weeks with assessments through Week 24. Participants dosed beyond Week 20 or who had entered Stage II discontinued treatment and completed an end of treatment/early termination visit 4 weeks after last dose, followed by safety follow-up visits.

A Phase 2 Proof of Concept Study to Evaluate the Efficacy and Safety of Daxdilimab in Participants With Dermatomyositis (DM) or Anti-synthetase Inflammatory Myositis (ASIM)

Total improvement score was derived from standardized clinical response criteria which was calculated by sum of improvement scores of 6 core set measures (CSMs) included physician global disease activity (PhGDA), patient global disease activity (PtGDA), manual muscle testing 8 (MMT8) bilateral, health assessment questionnaire-disability index (HAQ-DI), extramuscular global assessment (EGA), and laboratory muscle enzymes (LME). Total improvement score was ranged from 0 to 100, where higher scores indicated greater improvement. The TIS improvement categories are defined as minimal (TIS greater than or equal to \[≥\]20), moderate (TIS ≥40) and major improvement (TIS ≥60). Mean TIS at week 24 was reported in this outcome measure.

The percentage of participants who achieved moderate improvement (TIS ≥ 40), and do not experience confirmed disease deterioration at two consecutive visits through Week 24 were reported. Confirmed deterioration is defined as any of the following occurred at two consecutive visits compared with baseline: (i) Worsening of PhGDA by ≥ 2 cm and worsening of MMT8 by ≥ 20%, or (ii) Worsening of EGA by ≥ 2 cm, or (iii) Worsening of ≥ 3 of 5 core set measures (excluding laboratory enzymes) by ≥ 30%.

The percentage of participants who achieved minimal improvement (TIS ≥ 20), and do not experience confirmed disease deterioration at two consecutive visits through Week 24 were reported. Confirmed deterioration is defined as any of the following occurred at two consecutive visits compared with baseline: (i) Worsening of PhGDA by ≥ 2 cm and worsening of MMT8 by ≥ 20%, or (ii) Worsening of EGA by ≥ 2 cm, or (iii) Worsening of ≥ 3 of 5 core set measures (excluding laboratory enzymes) by ≥ 30%.

The CDASI activity score used to assess the severity of cutaneous DM and detect the improvement in disease activity. The CDASI activity score evaluates erythema, scale, and erosion/ulceration across 15 different body areas including the presence and severity of Gottron's papules on the hands, periungual changes and alopecia. The CDASI activity score ranges from 0 to 100 and higher scores indicate greater disease severity. A negative change from baseline indicates a reduction in disease severity.

The percentage of participants who received OCS dose ≥ 10 milligram per day (mg/day) of prednisone or equivalent at baseline and who achieved a clinically meaningful reduction in oral corticosteroid dose either: a 25% reduction or an OCS dose of 7.5 mg/day of prednisone or equivalent at Week 24 were reported.

Mean concentrations of DAX were reported. Values below the lower limit of quantitation (LLOQ) were set to zero before calculation of the descriptive statistics. If the calculated mean concentration from observed values was less than the LLOQ of the assay, the mean value was set to " below the limit of quantification (BLQ)".

Mean concentrations of DAX were reported. Values below the lower limit of quantitation (LLOQ) were set to zero before calculation of the descriptive statistics.

Number of participants who developed ADAs were reported. The ADA status was summarized by the categories included; ADA prevalence: ADA positive observed at least once during the trial (baseline included); Only baseline positive: ADA positive observed at baseline but not observed at any post-baseline; Only post-baseline positive (treatment-induced): ADA positive not observed at baseline but observed at least once post-baseline; Both baseline and post-baseline positive: ADA positive observed at both baseline and at least once post-baseline; Incidence (treatment emergent ADA): ADA positive post-baseline only or boosted their pre-existing ADA titer (≥ 4-fold increase) during the trial period.

An AE is any untoward medical occurrence in a clinical trial participant, temporally associated with the use of trial intervention, whether or not considered related to the trial intervention. If an AE occurs on or after the first dose of trial intervention, the AE was considered as a TEAE. An SAE is defined as any untoward medical occurrence that, at any dose results in death or is life-threatening or requires inpatient hospitalization or prolongation of existing hospitalization or results in persistent or significant disability/incapacity or is a congenital anomaly/birth defect. An AESI is an AE of scientific or medical concern specific to the trial intervention that requires ongoing monitoring and prompt communication by the investigator. AESIs in this trial were hypersensitivity reaction, including anaphylaxis, herpes zoster infection, severe viral infection/reactivation (CTCAE Grade 3 or higher), opportunistic infection, and malignancy (except non-melanoma skin cancer).

An AE is any untoward medical occurrence in a clinical trial participant, temporally associated with the use of trial intervention, whether or not considered related to the trial intervention. If an AE occurs on or after the first dose of trial intervention, the AE was considered as a TEAE. An SAE is defined as any untoward medical occurrence that, at any dose results in death or is life-threatening or requires inpatient hospitalization or prolongation of existing hospitalization or results in persistent or significant disability/incapacity or is a congenital anomaly/birth defect. An AESI is an AE of scientific or medical concern specific to the trial intervention that requires ongoing monitoring and prompt communication by the investigator. AESIs in this trial were hypersensitivity reaction, including anaphylaxis, herpes zoster infection, severe viral infection/reactivation (CTCAE Grade 3 or higher), opportunistic infection, and malignancy (except non-melanoma skin cancer).