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

Study Overview
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Brief Summary
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The reason for this long term study is to see how safe and effective the study drug known as baricitinib is in participants with systemic lupus erythematosus (SLE) who have completed the final treatment visit of study I4V-MC-JAHZ (NCT03616912) or study I4V-MC-JAIA (NCT03616964).

Official Title
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A Phase 3, Double-Blind, Multicenter Study to Evaluate the Long-Term Safety and Efficacy 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 completed the final treatment study visit of an originating study, such as study JAHZ (NCT03616912) or Study JAIA (NCT03616964).

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 one 2 mg Baricitinib tablet and one placebo tablet matching 4 mg Baricitinib administered orally every day (QD). | Drug: Baricitinib<br>* Administered orally.<br>* Other names: LY3009104;Drug: Placebo<br>* Administered orally.<br>|
| Experimental: 4 mg Baricitinib<br>Participants received one 4 mg Baricitinib tablet and one placebo tablet matching 2 mg Baricitinib administered orally QD. | Drug: Baricitinib<br>* Administered orally.<br>* Other names: LY3009104;Drug: Placebo<br>* Administered orally.<br>|
| Experimental: Placebo to 2 mg Baricitinib<br>Participants who received placebo in the originating study (JAHZ or JAIA) were randomized to receive 2 mg Baricitinib administered orally QD. | Drug: Baricitinib<br>* Administered orally.<br>* Other names: LY3009104;Drug: Placebo<br>* Administered orally.<br>|
| Experimental: Placebo to 4 mg Baricitinib<br>Participants who received placebo in the originating study (JAHZ or JAIA) were randomized to receive 4 mg Baricitinib administered orally QD. | Drug: Baricitinib<br>* Administered orally.<br>* Other names: LY3009104;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 With Treatment-Emergent Adverse Events (TEAEs) | Percentage of participants with TEAEs. A treatment-emergent AE (TEAE) is defined as an event that first occurred or worsened in severity after the first dose of study treatment in Study JAIM and on or prior to the last visit date during the analysis period. The analysis period is defined as the treatment period plus up to 30 days off-drug follow-up time. A summary of serious and other non-serious adverse events, regardless of causality, is located in the Reported Adverse Events module. | Week 134 | 
| Percentage of Participants With Adverse Events of Special Interest (AESIs) | Percentage of Participants with AESIs. AESI consisted of infections, positively adjudicated arterial thromboembolic events (ATE), positively adjudicated venous thromboembolic events (VTE), positively adjudicated major adverse cardiovascular events (MACE), other positively adjudicated cardiovascular events, death, anaphylactic reactions, hypersensitivity, angioedema, and malignancies. | Week 134 | 
| Percentage of Participants With Serious Adverse Events (SAEs) | Percentage of participants with SAEs. An SAE is any AE from this study that results in one of the following outcomes: Death; Initial or prolonged inpatient hospitalization; A life-threatening experience (that is, immediate risk of dying); Persistent or significant disability/incapacity; Congenital anomaly/birth defect; Important medical events that may not be immediately life-threatening or result in death or hospitalization, but may jeopardize the patient or may require intervention to prevent one of the other outcomes listed in the definition above. A summary of all SAE's, regardless of causality, is located in the Reported Adverse Events section. | Week 134 | 
| Percentage of Participants With Temporary Investigational Product Interruptions | Percentage of participants with temporary investigational product interruptions. | Week 134 | 
| Percentage of Participants With Permanent Investigational Product Discontinuations | Percentage of participants with permanent investigational product discontinuations. | Week 134 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving a Systemic Lupus Erythematosus Responder Index 4 (SRI-4) Response | 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 assesses disease activity on a visual analogue scale from 0 to 3 (1=mild, 2=moderate, 3=severe). | Week 134 | 
| Percentage of Participants Achieving a Lupus Low Disease Activity State (LLDAS) | Percentage of participants achieving a LLDAS. The LLDAS is a composite measure designed to identify patients achieving a state of low disease activity. The LLDAS response criteria were: (1) SLEDAI-2K <=4, with no activity in major organ systems (CNS, vascular, renal, cardiorespiratory and constitutional); where no activity is defined as all items of SLEDAI-2K within these major organ systems equal to 0. (2) no new features of lupus disease activity compared to previous occurred visit, where the new feature is defined as any of the SLEDAI-2K 24 items changed from 0 to greater than 0; (3) PGA (scale 0-3), <=1; (4) current prednisolone (or equivalent) dose <=7.5 mg daily. | Week 48 | 
| Change From Baseline in Prednisone Dose | Change from baseline in prednisone dose. | Baseline through Week 48 | 
| Annualized Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA)-Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) Flare Index Flare Rate | The SELENA-SLEDAI tool is a cumulative and weighted index used to assess disease activity across 24 different disease descriptors in patients with lupus. A patient's SELENA-SLEDAI total score is the sum of all marked lupus related descriptors (seizure, psychosis, organic brain syndrome, visual disturbance, cranial nerve disorder, lupus headache, cerebrovascular accident, vasculitis, arthritis, myositis, urinary casts, hematuria, proteinuria, pyuria, new rash, alopecia, mucosal ulcers, pleurisy, pericarditis, low complement, increased DNA binding, fever, thrombocytopenia, leukopenia). A total score can fall between 0 and 105, with a higher score representing a more significant degree of disease activity. The annualized flare rate is calculated as the number of flares divided by the flare exposure time in days multiplied with 365.25. | Baseline through Week 48 | 
| 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 | The CLASI is a single-page tool that separately quantifies disease activity and damage. For the activity score, points are given for the presence of erythema, scale, mucous membrane lesions, recent hair loss, and inflammatory alopecia. The total score represents the sum of the individual scores and ranges from 0 to 70. Higher scores are awarded for more severe manifestations. | Week 48 | 
| Change From Baseline in Tender Joint Count | The number of tender and painful joints is determined by examination of 28 joints (14 on each side) which include: the 2 shoulders, the 2 elbows, the 2 wrists, the 10 metacarpophalangeal joints, the 2 interphalangeal joints of the thumb, the 8 proximal interphalangeal joints, and the 2 knees. The joints are assessed and classified as tender or not tender. LS mean was calculated using Mixed Model Repeated Measures (MMRM) analysis with treatment, baseline disease activity (total SLEDAI-2K <10; >=10), baseline corticosteroid dose (<10 mg/day; >=10 mg/day prednisone or equivalent), region (North America, Central/South America/Mexico, Europe, Asia and Rest of World), visit (as categorical variable), baseline value, treatment-by-visit interaction, and baseline value-by-visit interaction. | Baseline through Week 48 | 
| Change From Baseline in Swollen Joint Count | The number of swollen joints is determined by examination of 28 joints (14 on each side) which include: the 2 shoulders, the 2 elbows, the 2 wrists, the 10 metacarpophalangeal joints, the 2 interphalangeal joints of the thumb, the 8 proximal interphalangeal joints, and the 2 knees. The joints are assessed and classified as swollen or not swollen. LS mean was calculated using MMRM analysis with treatment, baseline disease activity (total SLEDAI-2K <10; >=10), baseline corticosteroid dose (<10 mg/day; >=10 mg/day prednisone or equivalent), region (North America, Central/South America/Mexico, Europe, Asia and Rest of World), visit (as categorical variable), baseline value, treatment-by-visit interaction, and baseline value-by-visit interaction. | Baseline trough Week 48 | 
| Change From Baseline in Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index Total Score | The SLICC/ACR damage index is a validated instrument to assess damage, defined as irreversible impairment, continuously persistent for 6 months (ascertained by clinical assessment), occurring since the onset of lupus, and it is based on a weighted scoring system. This index records damage occurring in participants with SLE regardless of cause, with demonstrated content, face, criterion, and discriminant validity. A score of 0 indicates no damage. Total maximum score is 47 and increasing score indicates increasing disease severity. | Baseline through Week 48 | 
| Change From Baseline in Worst Pain Numeric Rating Scale (NRS) | Change from baseline in Worst Pain NRS. It is assessed using an 11-point Numeric Rating Scale (NRS) (0-10) where 0 represents no pain and 10 represents worst pain imaginable. Overall severity of a patient's pain is indicated by selecting the number that best describes the worst level of pain during the past 7 days. | Baseline through Week 48 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SLE