A Study Evaluating the Effects of GLPG3970 Given as Oral Treatment for 12 Weeks in Adults With Systemic Lupus Erythematosus

Study Overview
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Brief Summary
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This is a first exploration of GLPG3970 in subjects with active systemic lupus erythematosus (SLE) to evaluate the effect on disease biomarkers and to determine its pharmacokinetics (PK) profile, safety and tolerability, and pharmacodynamics (PD) biomarkers related to the investigational product (IP) mechanism of action and the pathophysiology of SLE.

Official Title
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A Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter Study to Evaluate the Pharmacodynamics, Pharmacokinetics, Safety, and Tolerability of Orally Administered GLPG3970 for 12 Weeks in Adult Subjects With Active Systemic Lupus Erythematosus

Conditions
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Systemic Lupus Erythematosus

Intervention / Treatment
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* Drug: GLPG3970 film-coated tablet
* Drug: Placebo film-coated tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: SLE diagnosis defined by American College of Rheumatology (ACR) 1997 criteria ≥4 Active arthritis in >=4 active joints (according to 28 joint count) and/or cutaneous lupus erythematosus disease area and severity index (CLASI) score >=6. Anti-dsDNA antibodies >15 IU/mL. Stable standard-of-care (SoC) therapy (defined as no change in prescription for at least 2 weeks prior to first IP dosing) consisting of the following permitted SoC medications: Corticosteroids <=20 mg/day (prednisone or equivalent) for at least 2 weeks prior to first IP dosing; AND/OR Non-steroidal anti-inflammatory drug (NSAIDs); AND/OR One single antimalarial at a stable dose (hydroxychloroquine <=5 mg/ kg/day, quinacrine 100 mg/day, or chloroquine 2.3 mg/kg/day) for at least 8 weeks prior to first IP dosing; AND/OR One single immunosuppressant at a stable dose (azathioprine (AZA) <=2 mg/kg/day, methotrexate (MTX) <=20 mg/week, or mycophenolate mofetil (MMF) <=2 g/day) for at least 8 weeks prior to first IP dosing. estimated glomerular filtration rate (eGFR) >=60 mL/min (according to Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)) This list only contains the key inclusion criteria. Exclusion Criteria: Lupus nephritis >= Class III Severe organ manifestation or life-threatening lupus disease (active severe central nervous system lupus, severe pleuro-pericarditis, severe vasculitis). Severe acute respiratory syndrome coronavirus disease 2 (SARS-CoV-2) infection >0 Unstable condition not related to SLE Systemic inflammatory condition other than SLE such as, but not limited to rheumatoid arthritis (RA), spondyloarthropathy, Crohn's disease, ulcerative colitis, or psoriatic arthritis Sjögren's syndrome and/or antiphospholipid antibody syndrome who do not require treatment with any prohibited medication are NOT excluded. Active systemic infection Poorly controlled chronic cardiac, pulmonary, or renal disease. Known or suspected history of or a current immunosuppressive condition, or a history of invasive opportunistic infections Treatment with disallowed therapies This list only contains the key exclusion criteria.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: GLPG3970<br>One dose level of GLPG3970 | Drug: GLPG3970 film-coated tablet<br>* GLPG3970 for oral administration<br>|
| Placebo Comparator: Placebo<br>One dose level of Placebo | Drug: Placebo film-coated tablet<br>* Placebo for oral administration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in biomarkers associated with disease anti-dsDNA | To characterize the PD of GLPG3970 compared to placebo in adult subjects with active SLE | Between Day 1 and 104 | 
| Change in biomarkers associated with disease complement component 3 (C3), and complement component 4 (C4) | To characterize the PD of GLPG3970 compared to placebo in adult subjects with active SLE | Between Day 1 and 104 | 
| Number, incidence, and severity of treatment-emergent adverse events (TEAEs) | To evaluate the safety and tolerability of GLPG3970 compared to placebo in adult subjects with active SLE | From screening through study completion, an average of 5 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Observed GLPG3970 plasma trough concentrations (Ctrough) | To characterize the PK of GLPG3970 in adult subjects with active SLE | Between Day 1 and 87 |