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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03843125
Recruitment Status : Terminated (Study terminated due to insufficient evidence to support a positive benefit: risk profile. Safety findings were consistent with previously published OLUMIANT data)
First Posted : February 15, 2019
Results First Posted : May 16, 2023
Last Update Posted : May 16, 2023
Sponsor:
Collaborator:
Incyte Corporation
Information provided by (Responsible Party):
Eli Lilly and Company

Study Description
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Brief Summary:
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).

Condition or disease Intervention/treatment Phase
Systemic Lupus Erythematosus Drug: Baricitinib Drug: Placebo Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1147 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 3, Double-Blind, Multicenter Study to Evaluate the Long-Term Safety and Efficacy of Baricitinib in Patients With Systemic Lupus Erythematosus (SLE)
Actual Study Start Date : September 9, 2019
Actual Primary Completion Date : April 1, 2022
Actual Study Completion Date : April 1, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lupus
Drug Information available for: Baricitinib

Arms and Interventions
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Arm Intervention/treatment
Experimental: 2 mg Baricitinib
Participants received one 2 mg Baricitinib tablet and one placebo tablet matching 4 mg Baricitinib administered orally every day (QD).
 Drug: Baricitinib
Administered orally.
Other Name: LY3009104

Drug: Placebo
Administered orally.
Experimental: 4 mg Baricitinib
Participants received one 4 mg Baricitinib tablet and one placebo tablet matching 2 mg Baricitinib administered orally QD.
 Drug: Baricitinib
Administered orally.
Other Name: LY3009104

Drug: Placebo
Administered orally.
Experimental: Placebo to 2 mg Baricitinib
Participants who received placebo in the originating study (JAHZ or JAIA) were randomized to receive 2 mg Baricitinib administered orally QD.
 Drug: Baricitinib
Administered orally.
Other Name: LY3009104

Drug: Placebo
Administered orally.
Experimental: Placebo to 4 mg Baricitinib
Participants who received placebo in the originating study (JAHZ or JAIA) were randomized to receive 4 mg Baricitinib administered orally QD.
 Drug: Baricitinib
Administered orally.
Other Name: LY3009104

Drug: Placebo
Administered orally.


Outcome Measures
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Primary Outcome Measures :
  1. Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: Week 134 ]

    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.


  2. Percentage of Participants With Adverse Events of Special Interest (AESIs) [ Time Frame: Week 134 ]
    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.

  3. Percentage of Participants With Serious Adverse Events (SAEs) [ Time Frame: Week 134 ]

    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.


  4. Percentage of Participants With Temporary Investigational Product Interruptions [ Time Frame: Week 134 ]
    Percentage of participants with temporary investigational product interruptions.

  5. Percentage of Participants With Permanent Investigational Product Discontinuations [ Time Frame: Week 134 ]
    Percentage of participants with permanent investigational product discontinuations.


Secondary Outcome Measures :
  1. Percentage of Participants Achieving a Systemic Lupus Erythematosus Responder Index 4 (SRI-4) Response [ Time Frame: Week 134 ]

    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).


  2. Percentage of Participants Achieving a Lupus Low Disease Activity State (LLDAS) [ Time Frame: Week 48 ]
    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.

  3. Change From Baseline in Prednisone Dose [ Time Frame: Baseline through Week 48 ]
    Change from baseline in prednisone dose.

  4. Annualized Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA)-Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) Flare Index Flare Rate [ Time Frame: Baseline through Week 48 ]
    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.

  5. 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 [ Time Frame: Week 48 ]
    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.

  6. Change From Baseline in Tender Joint Count [ Time Frame: Baseline through Week 48 ]
    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.

  7. Change From Baseline in Swollen Joint Count [ Time Frame: Baseline trough Week 48 ]
    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.

  8. Change From Baseline in Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index Total Score [ Time Frame: Baseline through Week 48 ]
    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.

  9. Change From Baseline in Worst Pain Numeric Rating Scale (NRS) [ Time Frame: Baseline through Week 48 ]
    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.


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Have completed the final treatment study visit of an originating study, such as study JAHZ (NCT03616912) or Study JAIA (NCT03616964).
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03843125


Locations
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Sponsors and Collaborators
Eli Lilly and Company
Incyte Corporation
Investigators
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Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST) Eli Lilly and Company
  Study Documents (Full-Text)

Documents provided by Eli Lilly and Company:
Study Protocol  [PDF] November 15, 2019
Statistical Analysis Plan  [PDF] November 30, 2021

More Information
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Additional Information:

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Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT03843125    
Other Study ID Numbers: 16832
I4V-MC-JAIM ( Other Identifier: Eli Lilly and Company )
2017-005028-11 ( EudraCT Number )
First Posted: February 15, 2019    Key Record Dates
Results First Posted: May 16, 2023
Last Update Posted: May 16, 2023
Last Verified: May 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
URL: https://vivli.org/

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Eli Lilly and Company:
SLE
Additional relevant MeSH terms:
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Lupus Erythematosus, Systemic
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases