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

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ClinicalTrials.gov Identifier: NCT02708095
Recruitment Status : Completed
First Posted : March 15, 2016
Results First Posted : November 21, 2018
Last Update Posted : November 21, 2018
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Systemic Lupus Erythematosus
Interventions Drug: Baricitinib
Drug: Placebo
Enrollment 314
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Placebo 2 mg Baricitinib 4 mg Baricitinib
Hide Arm/Group Description Participants received Placebo orally once daily (QD) for 24 weeks. Participants received 2 (milligrams) mg of Baricitinib tablet orally once a day for 24 weeks. Participants received 4 mg of Baricitinib tablet orally once a day for 24 weeks.
Period Title: Overall Study
Started 105 105 104
Received at Least 1 Dose of Study Drug 105 105 104
Completed 83 86 86
Not Completed 22 19 18
Reason Not Completed
Adverse Event             4             10             11
Lack of Efficacy             9             3             0
Lost to Follow-up             2             0             0
Physician Decision             2             3             2
Protocol Violation             0             0             1
Withdrawal by Subject             5             3             4
Arm/Group Title Placebo 2 mg Baricitinib 4 mg Baricitinib Total
Hide Arm/Group Description Participants received Placebo orally once daily (QD) for 24 weeks. Participants received 2 mg of Baricitinib tablet orally once a day for 24 weeks. Participants received 4 mg of Baricitinib tablet orally once a day for 24 weeks. Total of all reporting groups
Overall Number of Baseline Participants 105 105 104 314
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 105 participants 105 participants 104 participants 314 participants
44.9  (12.8) 43.2  (11.0) 45.0  (12.4) 44.3  (12.1)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 105 participants 105 participants 104 participants 314 participants
Female 99 96 99 294
Male 6 9 5 20
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 105 participants 105 participants 104 participants 314 participants
Hispanic or Latino 38 32 32 102
Not Hispanic or Latino 52 62 60 174
Unknown or Not Reported 15 11 12 38
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 105 participants 105 participants 104 participants 314 participants
American Indian or Alaska Native 9 6 10 25
Asian 20 20 20 60
Native Hawaiian or Other Pacific Islander 0 0 0 0
Black or African American 5 9 7 21
White 71 68 65 204
More than one race 0 1 1 2
Unknown or Not Reported 0 1 1 2
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 105 participants 105 participants 104 participants 314 participants
Puerto Rico 6 5 6 17
Argentina 9 12 7 28
Austria 3 2 3 8
South Korea 1 2 3 6
Romania 4 2 7 13
United States 31 34 30 95
Japan 13 10 10 33
Taiwan 6 7 5 18
Poland 13 10 9 32
Mexico 11 8 14 33
France 2 7 7 16
Spain 6 6 3 15
1.Primary Outcome
Title Percentage of Participants Who Achieve Remission of Arthritis and/or Rash Defined by the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K)
Hide Description 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.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least 1 dose of study drug with baseline and post-baseline values at the specified time point for remission of arthritis and/or rash.
Arm/Group Title Placebo 2 mg Baricitinib 4 mg Baricitinib
Hide Arm/Group Description:
Participants received Placebo orally once daily (QD) for 24 weeks.
Participants received 2 mg of Baricitinib tablet orally once a day for 24 weeks.
Participants received 4 mg of Baricitinib tablet orally once a day for 24 weeks.
Overall Number of Participants Analyzed 105 105 104
Measure Type: Number
Unit of Measure: Percentage of Participants
53.3 58.1 67.3
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, 2 mg Baricitinib
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.392
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.28
Confidence Interval (2-Sided) 95%
0.73 to 2.27
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, 4 mg Baricitinib
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.041
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.84
Confidence Interval (2-Sided) 95%
1.02 to 3.29
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Percentage of Participants Who Achieve SLE Responder Index 4 (SRI-4) Response
Hide Description 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).
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least 1 dose of study drug with baseline and post-baseline values at the specified time point for SRI-4 response.
Arm/Group Title Placebo 2 mg Baricitinib 4 mg Baricitinib
Hide Arm/Group Description:
Participants received Placebo orally once daily (QD) for 24 weeks.
Participants received 2 mg of Baricitinib tablet orally once a day for 24 weeks.
Participants received 4 mg of Baricitinib tablet orally once a day for 24 weeks.
Overall Number of Participants Analyzed 105 105 104
Measure Type: Number
Unit of Measure: Percentage of Participants
47.6 51.4 64.4
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, 2 mg Baricitinib
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.440
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio, log
Estimated Value 1.25
Confidence Interval (2-Sided) 95%
0.71 to 2.19
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, 4 mg Baricitinib
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.015
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.04
Confidence Interval (2-Sided) 95%
1.15 to 3.62
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Change From Baseline in SLEDAI-2K Score
Hide Description 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).
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least 1 dose of study drug with baseline and post-baseline values at the specified time point for SLEDAI-2K.
Arm/Group Title Placebo 2 mg Baricitinib 4 mg Baricitinib
Hide Arm/Group Description:
Participants received Placebo orally once daily (QD) for 24 weeks.
Participants received 2 mg of Baricitinib tablet orally once a day for 24 weeks.
Participants received 4 mg of Baricitinib tablet orally once a day for 24 weeks.
Overall Number of Participants Analyzed 86 88 86
Least Squares Mean (Standard Error)
Unit of Measure: Units on a scale
-3.82  (0.352) -4.07  (0.356) -4.39  (0.353)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, 2 mg Baricitinib
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.600
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference (Final Vaules)
Estimated Value -0.26
Confidence Interval (2-Sided) 95%
-1.23 to 0.71
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, 4 mg Baricitinib
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.243
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference (Final Vaules)
Estimated Value -0.58
Confidence Interval (2-Sided) 95%
-1.55 to 0.39
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Change From Baseline in Patient's Global Assessment of Disease Activity
Hide Description 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).
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least 1 dose of study drug with baseline and post-baseline values at the specified time point for Patient's Global Assessment of Disease Activity.
Arm/Group Title Placebo 2 mg Baricitinib 4 mg Baricitinib
Hide Arm/Group Description:
Participants received Placebo orally once daily (QD) for 24 weeks.
Participants received 2 mg of Baricitinib tablet orally once a day for 24 weeks.
Participants received 4 mg of Baricitinib tablet orally once a day for 24 weeks.
Overall Number of Participants Analyzed 84 86 86
Least Squares Mean (Standard Error)
Unit of Measure: Units on a scale
-0.67  (0.105) -0.83  (0.107) -1.00  (0.105)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, 2 mg Baricitinib
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.285
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference (Final Vaules)
Estimated Value -0.16
Confidence Interval (2-Sided) 95%
-0.45 to 0.13
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, 4 mg Baricitinib
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.026
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference (Final Vaules)
Estimated Value -0.33
Confidence Interval (2-Sided) 95%
-0.62 to -0.04
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Population Pharmacokinetics (PK): Area Under the Concentration-Time Curve of Baricitinib at Steady State (AUCτ, ss)
Hide Description 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.
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of study drug and had evaluable PK (pharmacokinetics) data.
Arm/Group Title 2 mg Baricitinib 4 mg Baricitinib
Hide Arm/Group Description:
Participants received 2 mg of Baricitinib tablet orally once a day for 24 weeks.
Participants received 4 mg of Baricitinib tablet orally once a day for 24 weeks.
Overall Number of Participants Analyzed 104 104
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nanogram*hour per milliliter (ng*h/mL)
265
(55%)
569
(50%)
6.Secondary Outcome
Title Population Pharmacokinetics (PK): Maximum Observed Drug Concentration at Steady State (Cmax,ss)
Hide Description 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.
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of study drug and had evaluable PK (pharmacokinetics) data.
Arm/Group Title 2 mg Baricitinib 4 mg Baricitinib
Hide Arm/Group Description:
Participants received 2 mg of Baricitinib tablet orally once a day for 24 weeks.
Participants received 4 mg of Baricitinib tablet orally once a day for 24 weeks.
Overall Number of Participants Analyzed 104 104
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nanogram per milliliter (ng/mL)
29.0
(30%)
59.2
(24%)
Time Frame Up to 32 weeks
Adverse Event Reporting Description All randomized participants who received at least 1 dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
 
Arm/Group Title Placebo 2 mg Baricitinib 4 mg Baricitinib
Hide Arm/Group Description Participants received Placebo orally once daily (QD) for 24 weeks. Participants received 2 mg of Baricitinib tablet orally once a day for 24 weeks. Participants received 4 mg of Baricitinib tablet orally once a day for 24 weeks.
All-Cause Mortality
Placebo 2 mg Baricitinib 4 mg Baricitinib
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/105 (0.00%)      0/105 (0.00%)      0/104 (0.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
Placebo 2 mg Baricitinib 4 mg Baricitinib
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   5/105 (4.76%)      11/105 (10.48%)      10/104 (9.62%)    
Blood and lymphatic system disorders       
Lymphadenopathy  1  0/105 (0.00%)  0 1/105 (0.95%)  1 0/104 (0.00%)  0
Cardiac disorders       
Angina pectoris  1  0/105 (0.00%)  0 1/105 (0.95%)  1 0/104 (0.00%)  0
Gastrointestinal disorders       
Diarrhoea  1  0/105 (0.00%)  0 0/105 (0.00%)  0 1/104 (0.96%)  1
Gastric ulcer  1  0/105 (0.00%)  0 0/105 (0.00%)  0 1/104 (0.96%)  1
Intestinal perforation  1  0/105 (0.00%)  0 0/105 (0.00%)  0 1/104 (0.96%)  1
Nausea  1  0/105 (0.00%)  0 0/105 (0.00%)  0 1/104 (0.96%)  1
Umbilical hernia  1  1/105 (0.95%)  1 0/105 (0.00%)  0 0/104 (0.00%)  0
Volvulus  1  0/105 (0.00%)  0 1/105 (0.95%)  1 0/104 (0.00%)  0
Infections and infestations       
Appendicitis  1  0/105 (0.00%)  0 0/105 (0.00%)  0 1/104 (0.96%)  1
Cellulitis  1  1/105 (0.95%)  1 0/105 (0.00%)  0 0/104 (0.00%)  0
Diverticulitis  1  0/105 (0.00%)  0 0/105 (0.00%)  0 1/104 (0.96%)  1
Influenza  1  0/105 (0.00%)  0 0/105 (0.00%)  0 1/104 (0.96%)  1
Pneumonia  1  0/105 (0.00%)  0 1/105 (0.95%)  1 2/104 (1.92%)  2
Tooth abscess  1  1/105 (0.95%)  1 0/105 (0.00%)  0 0/104 (0.00%)  0
Urinary tract infection  1  0/105 (0.00%)  0 1/105 (0.95%)  1 1/104 (0.96%)  1
Injury, poisoning and procedural complications       
Ankle fracture  1  1/105 (0.95%)  1 0/105 (0.00%)  0 0/104 (0.00%)  0
Joint dislocation  1  0/105 (0.00%)  0 1/105 (0.95%)  1 0/104 (0.00%)  0
Tibia fracture  1  1/105 (0.95%)  1 0/105 (0.00%)  0 1/104 (0.96%)  1
Investigations       
Lipase increased  1  0/105 (0.00%)  0 0/105 (0.00%)  0 1/104 (0.96%)  1
Musculoskeletal and connective tissue disorders       
Osteonecrosis  1  0/105 (0.00%)  0 0/105 (0.00%)  0 1/104 (0.96%)  1
Pain in extremity  1  0/105 (0.00%)  0 0/105 (0.00%)  0 1/104 (0.96%)  1
Nervous system disorders       
Migraine  1  0/105 (0.00%)  0 1/105 (0.95%)  1 0/104 (0.00%)  0
Syncope  1  0/105 (0.00%)  0 1/105 (0.95%)  1 0/104 (0.00%)  0
Pregnancy, puerperium and perinatal conditions       
Abortion  1  0/99 (0.00%)  0 1/96 (1.04%)  1 0/99 (0.00%)  0
Psychiatric disorders       
Anxiety  1  0/105 (0.00%)  0 1/105 (0.95%)  1 0/104 (0.00%)  0
Depression  1  0/105 (0.00%)  0 0/105 (0.00%)  0 2/104 (1.92%)  2
Mental status changes  1  0/105 (0.00%)  0 1/105 (0.95%)  1 0/104 (0.00%)  0
Renal and urinary disorders       
Acute kidney injury  1  0/105 (0.00%)  0 0/105 (0.00%)  0 1/104 (0.96%)  1
Lupus nephritis  1  1/105 (0.95%)  1 0/105 (0.00%)  0 0/104 (0.00%)  0
Reproductive system and breast disorders       
Cervical dysplasia  1  0/99 (0.00%)  0 1/96 (1.04%)  1 0/99 (0.00%)  0
Vascular disorders       
Deep vein thrombosis  1  0/105 (0.00%)  0 0/105 (0.00%)  0 1/104 (0.96%)  1
Hypertension  1  0/105 (0.00%)  0 1/105 (0.95%)  1 0/104 (0.00%)  0
1
Term from vocabulary, MedDRA 20.0
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo 2 mg Baricitinib 4 mg Baricitinib
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   27/105 (25.71%)      36/105 (34.29%)      32/104 (30.77%)    
Infections and infestations       
Pharyngitis  1  3/105 (2.86%)  3 6/105 (5.71%)  6 5/104 (4.81%)  5
Upper respiratory tract infection  1  6/105 (5.71%)  6 7/105 (6.67%)  7 8/104 (7.69%)  8
Urinary tract infection  1  11/105 (10.48%)  15 10/105 (9.52%)  12 9/104 (8.65%)  15
Viral upper respiratory tract infection  1  4/105 (3.81%)  5 10/105 (9.52%)  13 10/104 (9.62%)  12
Nervous system disorders       
Headache  1  3/105 (2.86%)  3 6/105 (5.71%)  8 3/104 (2.88%)  4
1
Term from vocabulary, MedDRA 20.0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Chief Medical Officer
Organization: Eli Lilly and Company
Phone: 800-545-5979
Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT02708095     History of Changes
Other Study ID Numbers: 16270
I4V-MC-JAHH ( Other Identifier: Eli Lilly and Company )
2015-004404-35 ( EudraCT Number )
First Submitted: March 10, 2016
First Posted: March 15, 2016
Results First Submitted: September 28, 2018
Results First Posted: November 21, 2018
Last Update Posted: November 21, 2018