A Study to Investigate the Efficacy and Safety of Brepocitinib in Adults With Dermatomyositis

Study Overview
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Brief Summary
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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.

Official Title
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A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Investigate the Efficacy and Safety of Oral Brepocitinib in Adults With Dermatomyositis

Conditions
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Dermatomyositis

Intervention / Treatment
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* Drug: Brepocitinib
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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 screening (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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Brepocitinib Dose Level 1 PO QD<br> | Drug: Brepocitinib<br>* Oral Brepocitinib<br>|
| Experimental: Brepocitinib Dose Level 2 PO QD<br> | Drug: Brepocitinib<br>* Oral Brepocitinib<br>|
| Placebo Comparator: Placebo PO QD<br> | Drug: Placebo<br>* Oral Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Improvement Score (TIS) at Week 52 | 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 | 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| TIS responder rate after 52 weeks of brepocitinib administration QD, in comparison to placebo | Proportion of responders, defined as achieving TIS ≥ 40 points (moderate improvement) at Week 52 | 52 weeks | 
| Change from baseline in HAQ Disability Index score at Week 52 | 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. | 52 weeks | 
| Cutaneous Dermatomyositis Area and Severity Index (CDASI) Activity Score after 52 weeks of brepocitinib administration QD, in comparison to placebo | Change from baseline in Cutaneous Dermatomyositis Area and Severity Index (CDASI) Activity score at Week 52. Cutaneous Dermatomyositis Disease Area and Severity Index Activity Score 0 to 100 with higher scores indicating a worse outcome. | 52 weeks | 
| Normalized change from baseline area under the concentration-time curve (AUC) in oral prednisone-equivalent dose through Week 52 |  | 52 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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brepocitinib, dermatomyositis, TYK2/JAK1 inhibitor, PF-06700841, PVT-2201