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

Phase 2
Completed
Conditions
Systemic Lupus Erythematosus
Interventions
Drug: Placebo
Registration Number
NCT02708095
Lead Sponsor
Eli Lilly and Company
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
314
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboPlaceboParticipants received Placebo orally once daily (QD) for 24 weeks.
2 mg BaricitinibBaricitinibParticipants received 2 (milligrams) mg of Baricitinib tablet orally once a day for 24 weeks.
4 mg BaricitinibBaricitinibParticipants received 4 mg of Baricitinib tablet orally once a day for 24 weeks.
Primary Outcome Measures
NameTimeMethod
Percentage of Participants Who Achieve Remission of Arthritis and/or Rash Defined by the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K)Week 24

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.

Secondary Outcome Measures
NameTimeMethod
Population Pharmacokinetics (PK): Maximum Observed Drug Concentration at Steady State (Cmax,ss)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

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.

Change From Baseline in SLEDAI-2K ScoreBaseline, Week 24

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).

Percentage of Participants Who Achieve SLE Responder Index 4 (SRI-4) ResponseWeek 24

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).

Change From Baseline in Patient's Global Assessment of Disease ActivityBaseline, Week 24

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).

Population Pharmacokinetics (PK): Area Under the Concentration-Time Curve of Baricitinib at Steady State (AUCτ, ss)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

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.

Trial Locations

Locations (32)

University of Arizona

🇺🇸

Tucson, Arizona, United States

Wallace Rheumatic Study Center

🇺🇸

Beverly Hills, California, United States

Medvin Clinical Research

🇺🇸

Covina, California, United States

TriWest Research Assocaites

🇺🇸

El Cajon, California, United States

University of California

🇺🇸

La Jolla, California, United States

Desert Medical Advances

🇺🇸

Palm Desert, California, United States

Inlande Rheumatology Clinical Trials

🇺🇸

Upland, California, United States

Denver Arthritis Center

🇺🇸

Denver, Colorado, United States

New Horizon Research Center

🇺🇸

Miami, Florida, United States

West Broward Rheumatology Associates, Inc

🇺🇸

Tamarac, Florida, United States

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University of Arizona
🇺🇸Tucson, Arizona, United States
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