A Study of Baricitinib (LY3009104) in Participants With Systemic Lupus Erythematosus (SLE)

Study Overview
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Brief Summary
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The main purpose of this study is to evaluate the efficacy and safety of the study drug known as baricitinib in participants with systemic lupus erythematosus.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Parallel- Group, Phase 2 Study of Baricitinib in Patients With Systemic Lupus Erythematosus (SLE)

Conditions
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Systemic Lupus Erythematosus

Intervention / Treatment
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* Drug: Baricitinib
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have received a diagnosis of SLE at least 24 weeks prior to screening, meeting the American College of Rheumatology (ACR) 1982 revised criteria OR the 2012 Systemic Lupus Erythematosus International Collaborating Clinics (SLICC) criteria. Have a positive antinuclear antibody (ANA) (titer ≥1:80) and/or a positive anti-double-stranded deoxyribonucleic acid (dsDNA) as assessed by a central laboratory at screening. Have a SLEDAI-2K score ≥4 based on clinical symptoms (not including lab values) at randomization. Have active arthritis and/or active rash as defined by the SLEDAI-2K at randomization. Exclusion Criteria: Have active severe lupus nephritis. Have active severe central nervous system (CNS) lupus. Have a history or presence of cardiovascular, respiratory, hepatic, gastrointestinal, endocrine, hematological, neurological, or neuropsychiatric disorders or any other serious and/or unstable illness that, in the opinion of the investigator, could constitute an unacceptable risk when taking investigational product or interfere with the interpretation of data. Have a current or recent clinically serious viral, bacterial, fungal, or parasitic infection. Are currently receiving oral corticosteroids at doses >20-milligrams per day of prednisone (or equivalent) or have adjusted the dose of corticosteroids within 2 weeks of planned randomization. Have started treatment with or adjusted the dose of nonsteroidal anti-inflammatory drugs (NSAIDs) (for which the NSAID use is intended for treatment of signs and symptoms of SLE) within 4 weeks of planned randomization. Have started treatment with or adjusted the dose of an antimalarial within 12 weeks of planned randomization. Have started treatment with or adjusted the dose of an immunosuppressant within 12 weeks of planned randomization. Have received cyclophosphamide (or any other cytotoxic agent) within 12 weeks prior to screening.

Ages Eligible for Study
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Minimum Age: 18 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 2 mg Baricitinib<br>Participants received 2 (milligrams) mg of Baricitinib tablet orally once a day for 24 weeks. | Drug: Baricitinib<br>* Administered orally<br>* Other names: LY3009104;|
| Experimental: 4 mg Baricitinib<br>Participants received 4 mg of Baricitinib tablet orally once a day for 24 weeks. | Drug: Baricitinib<br>* Administered orally<br>* Other names: LY3009104;|
| Placebo Comparator: Placebo<br>Participants received Placebo orally once daily (QD) for 24 weeks. | Drug: Placebo<br>* Administered orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Achieve Remission of Arthritis and/or Rash Defined by the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) | Participants were defined as responder as follows using SLEDAI-2K definitions of arthritis and rash. If only arthritis is present at baseline, then arthritis must be absent at Week 24 to meet the primary endpoint. If only rash is present at baseline, then rash must be absent at Week 24 to meet the primary endpoint. If both arthritis and rash are present at baseline, then the primary endpoint is met if either arthritis, or rash, or both arthritis and rash are absent at Week 24. | Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Achieve SLE Responder Index 4 (SRI-4) Response | SRI-4 response is defined as: 1) Reduction of ≥4 points from baseline in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score; 2) no new British Isles Lupus Assessment Group (BILAG) A or no more than 1 new BILAG B disease activity scores; and 3) no worsening (defined as an increase of ≥0.3 points [10 mm] from baseline) in Physician's Global Assessment of Disease Activity. The SRI-4 is a composite index used to assess disease activity in SLE. SLEDAI-2K assessment consists of 24 items with total score of 0 to 105, with higher scores representing increased disease activity. BILAG Index: assessing clinical signs, symptoms, or laboratory parameters related to SLE, divided into 9 organ systems. For each organ system: A=severe disease, B=moderate disease, C=mild stable disease, D=inactive, but previously active, E=inactive and never affected. PGA is a visual analog scale scored from 0 to 3 (0=none, 1=mild, 2=moderate, 3=severe). | Week 24 | 
| Change From Baseline in SLEDAI-2K Score | SLE Disease Activity Index 2000 (SLEDAI-2K) score is a weighted, cumulative index of lupus disease activity. SLEDAI-2K is calculated from 24 individual descriptors across 9 organ systems; 0 indicates inactive disease and the maximum theoretical score is 105. Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with baseline of response, region, baseline disease activity (SLEDAI-2K <10, >=10), baseline anti-dsDNA status (positive, negative), treatment, time, treatment*time (type III sum of squares). | Baseline, Week 24 | 
| Change From Baseline in Patient's Global Assessment of Disease Activity | The Patient's Global Assessment of Disease Activity is a single-item, patient reported scale developed for the assessment of the patient's overall rating of their disease activity due to SLE. The scale measures disease activity through a 5 point Likert scale ranging from 0 (No disease activity) to 4 (Severe disease activity) at its worst over the past 7 days. LS mean was determined by MMRM model with baseline of response, region, baseline disease activity (SLEDAI-2K <10, >=10), baseline anti-dsDNA status (positive, negative), treatment, time, treatment*time (type III sum of squares). | Baseline, Week 24 | 
| Population Pharmacokinetics (PK): Area Under the Concentration-Time Curve of Baricitinib at Steady State (AUCτ, ss) | Plasma samples for pharmacokinetic (PK) analysis were obtained in week 0, week 4, week 8, week 16 and 24. AUC takes all time points post dose into account and one value is reported. | Week (Wk) 0: 15-30 minutes (min) postdose; Wk 4: Predose, 1.5 - 4 hour (hr) postdose; Wk 8: 1 - 3 hr postdose; Wk 16: Predose | 
| Population Pharmacokinetics (PK): Maximum Observed Drug Concentration at Steady State (Cmax,ss) | Plasma samples for pharmacokinetic (PK) analysis were obtained in week 0, week 4, week 8, week 16 and 24. Cmax takes all time points post dose into account and one value is reported. | Week (Wk) 0: 15-30 minutes (min) postdose; Wk 4: Predose, 1.5 - 4 hour (hr) postdose; Wk 8: 1 - 3 hr postdose; Wk 16: Predose |