A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Phase 3 Study of Baricitinib in Patients With Systemic Lupus Erythematosus
Overview
- Phase
- Phase 3
- Intervention
- Placebo
- Conditions
- Systemic Lupus Erythematosus
- Sponsor
- Eli Lilly and Company
- Enrollment
- 830
- Locations
- 183
- Primary Endpoint
- Percentage of Participants Achieving a Systemic Lupus Erythematosus Responder Index 4 (SRI-4) Response (4 mg Baricitinib)
- Status
- Terminated
- Last Updated
- 3 years ago
Overview
Brief Summary
The reason for this study is to see how effective and safe the study drug known as baricitinib is in participants with systemic lupus erythematosus (SLE).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Have a clinical diagnosis of SLE at least 24 weeks prior to screening.
- •Have documentation of having met at least 4 of 11 Revised Criteria for Classification of Systemic Lupus Erythematosus according to the 1997 Update of the 1982 American College of Rheumatology (ACR) criteria for classification of SLE prior to randomization.
- •Have a positive antinuclear antibody (ANA) (titer ≥1:80) and/or a positive anti-double-stranded deoxyribonucleic acid (dsDNA), and/or a positive anti-Smith (anti-Sm) as assessed by a central laboratory during screening.
- •Have a total Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score ≥6 during screening.
- •Have a clinical SLEDAI-2K score ≥4 at randomization.
- •Have at least 1 British Isles Lupus Assessment Group (BILAG) A score or 2 BILAG B scores during screening.
- •Are receiving at least one of the following standard of care medications for SLE:
- •A single antimalarial at a stable dose for at least 8 weeks prior to screening
- •A single immunosuppressant at a stable dose for at least 8 weeks prior to screening
- •An oral corticosteroid, initiated at least 4 weeks prior to screening, at a stable dose ≤40 milligrams/day prednisone (or equivalent) for at least 2 weeks prior to screening. If the participant is not receiving an antimalarial or immunosuppressant, the dose of corticosteroid must be ≥7.5 milligrams/day prednisone (or equivalent)
Exclusion Criteria
- •Have severe active lupus nephritis.
- •Have active 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.
- •Have received cyclophosphamide (or any other cytotoxic agent) within 12 weeks prior to screening.
Arms & Interventions
Placebo
Participants received two placebo tablets: one matching baricitinib 4 milligram (mg) and one matching baricitinib 2 mg administered orally every day (QD) for 52 weeks.
Intervention: Placebo
2 mg Baricitinib
Participants received one Baricitinib 2 mg tablet and one placebo tablet matching Baricitinib 4 mg administered QD for 52 weeks.
Intervention: Baricitinib
2 mg Baricitinib
Participants received one Baricitinib 2 mg tablet and one placebo tablet matching Baricitinib 4 mg administered QD for 52 weeks.
Intervention: Placebo
4 mg Baricitinib
Participants received one Baricitinib 4 mg tablet and one placebo tablet matching baricitinib 2 mg administered orally every day (QD) for 52 weeks.
Intervention: Baricitinib
4 mg Baricitinib
Participants received one Baricitinib 4 mg tablet and one placebo tablet matching baricitinib 2 mg administered orally every day (QD) for 52 weeks.
Intervention: Placebo
Placebo Maximum Extended Enrollment (MEE)
Participants received two placebo tablets: one matching baricitinib 4 mg and one matching baricitinib 2 mg administered orally QD for 52 weeks.
Intervention: Placebo
2 mg Baricitinib (MEE)
Participants received one Baricitinib 2 mg tablet and 1 placebo tablet matching Baricitinib 4 mg administered QD for 52 weeks.
Intervention: Baricitinib
2 mg Baricitinib (MEE)
Participants received one Baricitinib 2 mg tablet and 1 placebo tablet matching Baricitinib 4 mg administered QD for 52 weeks.
Intervention: Placebo
4 mg Baricitinib (MEE)
Participants received one Baricitinib 4 mg tablet and one placebo tablet matching baricitinib 2 mg administered orally every day (QD) for 52 weeks.
Intervention: Baricitinib
4 mg Baricitinib (MEE)
Participants received one Baricitinib 4 mg tablet and one placebo tablet matching baricitinib 2 mg administered orally every day (QD) for 52 weeks.
Intervention: Placebo
Outcomes
Primary Outcomes
Percentage of Participants Achieving a Systemic Lupus Erythematosus Responder Index 4 (SRI-4) Response (4 mg Baricitinib)
Time Frame: Week 52
SRI-4 response defined as 1)greater than or equal to (\>=) 4-point reduction in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) total score 2)no new British Isles Lupus Assessment Group (BILAG) A and no more than 1 new BILAG B domain score and 3)no worsening in Physician Global Assessment (PGA) of Disease Activity (worsening defined as an increase of \>=0.3 from baseline on a 0-3 visual analogue scale). SLEDAI-2K assessment consists of 24 items with total score of 0(no symptoms) to 105 (presence of all defined symptoms) with higher scores representing increased disease activity. BILAG Index: assessing clinical signs, symptoms,or laboratory parameters related to Systemic Lupus Erythematosus (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 assess disease activity on a visual analogue scale from 0 to 3 (1=mild, 2=moderate, 3=severe).
Secondary Outcomes
- Time to First Severe Flare(Baseline to Week 52)
- Change From Baseline in Worst Pain Numeric Rating Scale (NRS)(Baseline, Week 52)
- Percentage of Participants Whose Average Prednisone Dose Had Been Reduced by >=25% From Baseline to <=7.5 mg/Day During Weeks 40 Through 52 in Participants Receiving Greater Than 7.5 mg/Day at Baseline(Baseline, Week 40 through Week 52)
- Percentage of Participants With Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) Total Activity Score ≥10 at Baseline With ≥50% Reduction in CLASI Total Activity Score(Week 52)
- Change From Baseline in Swollen Joint Count(Baseline, Week 52)
- Change From Baseline in Tender Joints Count(Baseline, Week 52)
- Population Pharmacokinetics (PK): Area Under the Concentration-Time Curve of Baricitinib at Steady State (AUCτ, ss)(Week 0 (Baseline): 15 minutes (min) and 60 min postdose; Week 4: 2 to 4 hours (hr) postdose; Week 8: 4 to 6 hr postdose; Week 12 and Week 16 predose)
- Percentage of Participants Achieving SRI-4 Response - 2 mg Baricitinib(Week 52)
- Percentage of Participants Achieving a Lupus Low Disease Activity State (LLDAS)(Week 52)
- Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Total Score(Baseline, Week 52)
- Population PK: Maximum Observed Drug Concentration at Steady State (Cmax,ss)(Week 0 (Baseline): 15 minutes (min) and 60 min postdose; Week 4: 2 to 4 hours (hr) postdose; Week 8: 4 to 6 hr postdose; Week 12 and Week 16 predose)