A Study Evaluating the Effects of GLPG3667 Given as Oral Treatment for up to 24 Weeks in Adults With Dermatomyositis

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy, safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of orally administered GLPG3667 once daily for 24 weeks in adult participants with dermatomyositis (DM).

Official Title
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A Randomized, Double-blind, Placebo-controlled, Multi-center Study to Evaluate the Efficacy, Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Orally Administered GLPG3667 Once Daily for 24 Weeks in Adult Subjects With Dermatomyositis

Conditions
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Dermatomyositis

Intervention / Treatment
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* Drug: GLPG3667
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Participant has probable or definite DM in accordance with the ACR/EULAR criteria for at least 3 months. Participant with DM diagnosed in the 3 years prior to screening must have undergone cancer screening (according to local standard of care or applicable guidelines) within 1 year prior to screening. Note: The evidence of cancer screening must be documented. Participant must present objective evidence of active disease as defined by fulfilling 1 of the criteria below (as confirmed by the sponsor): DM rash as defined by modified-Cutaneous Dermatomyositis Disease Area and Severity Index Activity Score (m-CDASI-A) ≥ 6 at screening, or Creatine kinase (CK) > 4x upper limit of normal (ULN) at screening, or muscle biopsy evidence of active disease within 3 months prior to screening (defined as presence of active inflammation in muscle biopsy), or muscle magnetic resonance imaging showing active inflammation (edema) of the proximal skeletal muscles within 3 months prior to screening, or electromyography showing acute changes, such as spontaneous activity and myopathic changes not explained by other diseases within 3 months prior to screening, or any other clinical evidence of active disease as confirmed by the steering committee. Participant has reduced muscle strength (defined as Manual Muscle Test-8 < 142/150) and at least 2 additional abnormal core set measurements out of the following 5 at screening: Physician's Global Disease Activity score > 2/10 cm on the visual analog scale (VAS), Patient's Global Disease Activity score > 2/10 cm on VAS, extra-muscular disease activity > 2/10 cm on VAS, Health Assessment Questionnaire-Disability Index score > 0.25, elevated muscle enzymes (e.g. aldolase, CK, ALT, AST, and lactate dehydrogenase) with at least 1 muscle enzyme > 1.5x ULN. Participant previously demonstrated failure to or intolerance to first-line treatment (defined as oral corticosteroid[s] and at least 1 other immunosuppressant/ hydroxychloroquine) OR active disease despite treatment with first-line drugs. Currently, the participant is receiving maximum 2 treatments for DM (oral corticosteroid[s] and/or allowed immunosuppressant[s]/hydroxychloroquine) for at least 3 months and is on a stable dose (defined as no change in dose, type of administration, or dose regimen) for at least 4 weeks prior to screening and during screening within maximum allowed doses as specified in the study protocol. Note: Participants receiving 1 or no concomitant treatment for DM are also eligible. Key Exclusion Criteria: Participant has cancer-associated myositis (defined as myositis diagnosed within 2 years of cancer diagnosis with the exception of basal cell carcinoma, squamous cell carcinoma of the skin, or in situ uterine cervical carcinoma that has been excised and cured). Note: At least 1 year for basal cell carcinoma and squamous cell carcinoma or 5 years for in situ uterine cervical carcinoma must have passed since the excision. Participant has other causes of myositis (e.g. connective tissue disease) associated DM, polymyositis, juvenile DM, inclusion body myositis, or necrotizing idiopathic inflammatory myopathies (with or without rash) with the exception of overlap with secondary Sjogren's syndrome. Participant has permanent muscle weakness due to muscle damage (e.g. participant is wheelchair bound or has significant muscle atrophy on magnetic resonance imaging [MRI]) or a non-DM cause (drug-induced myopathy, including glucocorticoid-induced myopathy as primary cause of muscle weakness), according to investigator's judgement. Participant has taken any prohibited therapies within the defined washout periods before screening, and during screening as listed in the study protocol.

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GLPG3667<br>Participants will receive GLPG3667 dose A orally once daily for 24 weeks. | Drug: GLPG3667<br>* GLPG3667 capsules will be administered per dose and schedule specified in the arm description.<br>|
| Placebo Comparator: Placebo<br>Participants will receive placebo matching to GLPG3667 orally once daily for 24 weeks. | Drug: Placebo<br>* Placebo matching to GLPG3667 capsules will be administered per schedule specified in the arm description.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With at Least Minimal Improvement at Week 24 According to the American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) Criteria | Minimal improvement per ACR/EULAR was defined as total improvement score [TIS] of ≥ 20 points. The TIS is a score derived from the evaluation of the results from 6 core set measurements (CSMs) of myositis disease activity: Physician's Global Disease Activity Assessment; Patient's Global Disease Activity Assessment; Muscle Manual Test-8 (MMT-8); Health Assessment Questionnaire-Disability Index (HAQ-DI); Enzymes (aldolase, creatine kinase [CK], alanine aminotransferase [ALT], aspartate aminotransferase [AST], and lactate dehydrogenase [LDH]); and Extra-muscular disease activity. The TIS is a scale from 0 to 100 that allows for the discrimination between minimal, moderate and major responders depending on their improvement in the combined 6 CSM. | Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Modified-Cutaneous DM Disease Area and Severity Index Activity Score (m-CDASI-A) at Week 24 | The CDASI is a clinician-scored single page instrument that separately measures activity (m-CDASI-A) and damage (m-CDASI-D) in the skin of DM participants. The m-CDASI-A consists of 3 activity measures (erythema, scale, and erosion/ulceration) assessed over 15 body areas along with the activity of Gottron's papules on hands and activity of periungual changes and alopecia. m-CDASI-A ranges from 0-100. Higher scores indicate more disease activity. | Week 24 | 
| Change from baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 24 | The HAQ-DI is a generic rather than a disease-specific instrument, comprised of 8 sections: dressing, arising, eating, walking, hygiene, reach, grip, and activities. There are 2 or 3 questions for each section. Scoring within each section is from 0 [without any difficulty] to 3 [unable to do]. For each section the score given to that section is the worst score within the section. The 8 scores of the 8 sections are summed and divided by 8. | Week 24 | 
| Change from baseline in the manual muscle test (MMT-8) at Week 24 | MMT-8 is a set of 8 designated muscles, 7 of them being tested bilaterally (potential score 0-140). Axial (neck flexors) testing is included, so that potential maximum MMT-8 score = 150. | Week 24 | 
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (SAEs), and TEAEs Leading to Treatment Discontinuation |  | Baseline (Day 1) up to Week 24 | 
| Maximum Plasma Concentration (Cmax) of GLPG3667 |  | Week 4 | 
| Area Under the Plasma Concentration-Time Curve (AUC) of GLPG3667 |  | Week 4 | 
| Plasma Trough Concentration (Ctrough) at Steady State of GLPG3667 |  | Week 2 predose until Week 24 |