Dermatomyositis
Conditions
Keywords
brepocitinib, dermatomyositis, TYK2/JAK1 inhibitor, PF-06700841, PVT-2201
Brief summary
This is a phase 3, multicenter, randomized, placebo-controlled, double-blind study of treatment with brepocitinib (TYK2/JAK1 inhibitor) in adults with dermatomyositis (DM). The primary objective of this study is to assess the efficacy of two dose levels of brepocitinib in comparison to placebo, as measured by differences in the Total Improvement Score (TIS). After 52 weeks of double-blind treatment, participants have the option to continue therapy in a 52 week open-label extension phase where all participants will receive brepocitinib.
Interventions
DRUGBrepocitinib
Oral Brepocitinib
DRUGPlacebo
Oral Placebo
Sponsors
Priovant Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* A diagnosis of dermatomyositis according to 2017 EULAR/ACR Classification Criteria for Idiopathic Inflammatory Myopathies * Adult subjects (18-75 years old) * Active muscle and skin disease at screening and baseline * Prior therapy OR current therapy with corticosteroids, hydroxychloroquine, and/or one non-steroid immunosuppressant * Weight \> 40 kg to \< 130 kg, and with a body mass index (BMI) \< 40 kg/m2.
Exclusion criteria
* Dermatomyositis with end-stage organ involvement * Dermatomyositis with irreversible muscle involvement * History of: * Any lymphoproliferative disorder * Active malignancy; * History of cancer within 5 years prior to randomization (exceptions for basal cell carcinoma, squamous cell carcinoma, ductal carcinoma in situ of the breast, carcinoma in situ of the uterine cervix, or thyroid carcinoma.) * Cancer-associated dermatomyositis * Overlap myositis/connective tissue disease (except for overlap with Sjögren's syndrome) * Participants at a risk of thrombosis or cardiovascular disease * Participants with a high risk for herpes zoster reactivation * Participants with active or recent infections
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Improvement Score (TIS) at Week 52 | 52 weeks | TIS is a composite endpoint based on improvement in the 6 Disease Activity Core Set Measure (CSM) scores and ranges from 0 to 100 (2016 American College of Rheumatology \[ACR\] Myositis Response Criteria/European League Against Rheumatism \[EULAR\]) where a higher score indicates more improvement |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Dermatomyositis Outcomes for Muscle and Skin (DMOMS) at Week 52 | 52 weeks | DMOMS is a composite endpoint based on 4 component measures and ranges from 0 to 100 (Pandya, 2024) where a higher score indicates more improvement. |
| The proportion of participants achieving TIS ≥ 40 points (moderate improvement) at Week 52 | 52 weeks | — |
| Time to achievement of consecutive (≥ 2 visits) TIS ≥ 40 points (moderate improvement) by Week 52 | 52 weeks | — |
| The proportion of participants, regardless of baseline corticosteroid use, achieving TIS ≥ 40 points (moderate improvement) at Week 52 with 0 to ≤ 2.5 mg/day of oral prednisone (or equivalent) at both Week 48 and Week 52 | 52 weeks | — |
| Change from baseline in Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) Activity Score at Week 52 | 52 weeks | CDASI Activity Score 0 to 100 with higher scores indicating a worse outcome. |
| The proportion of participants achieving TIS ≥ 60 points (major improvement) at Week 52 | 52 weeks | — |
| Change from baseline in HAQ Disability Index score at Week 52 | 52 weeks | Change from baseline in HAQ Disability Index score at Week 52. Health Assessment Questionnaire (HAQ) Disability Index: Score for function and disability from 0 \[without any difficulty\] to 3 \[unable to do\]. Higher score associated with worse outcome. |
| Change from baseline in CDASI Activity Score at Week 4 | 4 weeks | — |
| The proportion of participants achieving ≥ 40% improvement with a ≥ 4-point improvement from baseline in CDASI Activity Score at Week 52 | 52 weeks | — |
Countries
Argentina, Belgium, Bulgaria, Canada, Chile, Czechia, Germany, Hungary, Israel, Italy, Mexico, Netherlands, Poland, Portugal, Romania, Serbia, South Korea, Spain, Taiwan, Turkey (Türkiye), United Kingdom, United States
Outcome results
None listed