The primary efficacy objective: To evaluate the effect of daxdilimab compared with placebo in reducing disease activity at Week 24. The secondary efficacy objectives include: 1. To evaluate the effect of daxdilimab compared with placebo in reducing disease activity at Week 24. 2. To evaluate the effect of daxdilimab compared with placebo on skin symptoms at Week 24. 3. To evaluate the effect of daxdilimab on decreasing the use of corticosteroid at Week 24. Other secondary objectives include: 1. To characterize the pharmacokinetics (PK) and immunogenicity of daxdilimab in participants. 2. To evaluate the safety and tolerability of daxdilimab in participants.
The study will enroll participants with 2 idiopathic inflammatory myositis populations: * Population 1 or dermatomyositis (DM): participants with DM with definite or probable myositis according to the American College of Rheumatology/European League Against Rheumatism 2017 (ACR/EULAR 2017) criteria and a DM rash. * Population 2 or anti-synthetase inflammatory myositis (ASIM): participants with ASIM with definite or probable myositis according to ACR/EULAR 2017 criteria and a positive ASIM associated antibody. Participants will be randomized by population in a 1:1 ratio and receive investigational product (IP) daxdilimab or placebo by subcutaneous injection. The estimated total study duration will be up to 36 weeks (up to 60 weeks for those participants who entered the open-label extension prior to amendment 2.) Acquired from Horizon in 2024.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
12
Participants will be administered daxdilimab by subcutaneous (SC) injection.
Participants will be administered identically matching placebo by SC injection.
Advanced Research Center, Inc.
Anaheim, California, United States
Centro Mineiro de Pesquisa - CMiP
Juiz de Fora, Minas Gerais, Brazil
LMK Servicos Medicos SS
Porto Alegre, Rio Grande do Sul, Brazil
Revmatologicky ustav
Prague, Praha, Hlavní Mesto, Czechia
Unidad de Investigacion de las Enfermedades Reumaticas S.A. De C.V.
Mexico City, Mexico
Accelerium, S. de R.L. de C.V. - PPDS
Monterrey, Mexico
Hospital Quironsalud Infanta Luisa
Seville, Spain
Aintree University Hospital - NWCRN - PPDS
Liverpool, Merseyside, United Kingdom
Western General Hospital Edinburgh - PPDS
Edinburgh, Midlothian, United Kingdom
Efficacy of daxdilimab compared to placebo as measured by Total Improvement Score (TIS)
TIS is a composite endpoint based on improvement in the 6 Disease Activity Core Set Measure (CSM) scores and range from 0 to 100 (2016 European League Against Rheumatism \[EULAR\]/American College of Rheumatology \[ACR\] Myositis Response Criteria) where a higher score is indicative of more improvement
Time frame: At Week 24
Proportion of participants with improvement of TIS ≥ 40 and without deterioration at 2 consecutive visits at 24 weeks
TIS is a composite endpoint based on improvement in the 6 Disease Activity Core Set Measure (CSM) scores and range from 0 to 100 (2016 European League Against Rheumatism \[EULAR\]/American College of Rheumatology \[ACR\] Myositis Response Criteria) where a higher score is indicative of more improvement
Time frame: At 24 Weeks
Proportion of participants with improvement of TIS ≥ 20 and without deterioration at 2 consecutive visits at 24 weeks
TIS is a composite endpoint based on improvement in the 6 Disease Activity Core Set Measure (CSM) scores and range from 0 to 100 (2016 European League Against Rheumatism \[EULAR\]/American College of Rheumatology \[ACR\] Myositis Response Criteria) where a higher score is indicative of more improvement
Time frame: At 24 Weeks
Change in the cutaneous dermatomyositis disease area and severity index (CDASI) activity score from Baseline (Day 1) to Week 24
The CDASI is used to assess the severity of cutaneous DM and detect improvement in disease activity. The scale rates disease involvement in 15 different body areas using 3 activity (erythema, scale, erosion/ulceration) and 2 damage (poikiloderma, calcinosis) measures. The activity score ranges from 0 to 100 and the damage score from 0 to 32. Higher scores indicate greater disease severity
Time frame: Baseline (Day1) to Week 24
Proportion of participants on an oral corticosteroid (OCS) dose ≥ 10 mg of prednisone or equivalent at baseline who achieve a clinically meaningful reduction in the OCS dose at Week 24
A clinically meaningful reduction is measured as either a 25% decrease or an OCS dose of 7.5 mg/day of prednisone or equivalent
Time frame: Baseline to Week 24
Serum concentration of daxdilimab over time
Time frame: Baseline to Week 56
Proportion of the participants with anti-drug antibodies (ADA) positive post-baseline only or boosted their pre-existing ADA during the study period.
Time frame: Baseline to Week 56
Incidence of ADA directed against daxdilimab over time
Time frame: Baseline to Week 56
Titer of ADA to daxdilimab over time
Time frame: Baseline to Week 56
Incidence of treatment emergent adverse events (TEAEs)
Time frame: Baseline to Week 56
Incidence of treatment emergent serious adverse events (TESAEs)
Time frame: Baseline to Week 56
Incidence of treatment emergent adverse events of special interest (TEAESIs)
TEAESIs including hypersensitivity reactions, anaphylaxis, herpes zoster infection, severe \[(common terminology criteria for adverse events (CTCAE)\] Grade 3 or higher) viral infection/reactivation, opportunistic infection, and malignancy (except non melanoma skin cancer)
Time frame: Baseline to Week 56
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