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

• Sponsor: Eli Lilly and Company
• Collaborator: Incyte Corporation
• Information provided by (Responsible Party): Eli Lilly and Company

Study Description

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).

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)
Estimated Enrollment :	750 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Double (Participant, Investigator)
Primary Purpose:	Treatment
Official Title:	A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Phase 3 Study of Baricitinib in Patients With Systemic Lupus Erythematosus
Actual Study Start Date :	August 2, 2018
Estimated Primary Completion Date :	February 16, 2021
Estimated Study Completion Date :	February 16, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Baricitinib High Dose; Baricitinib administered orally. Placebo administered orally to maintain the blind.	Drug: Baricitinib; Administered orally.; Other Name: LY3009104; Drug: Placebo; Administered orally
Experimental: Baricitinib Low Dose; Baricitinib administered orally. Placebo administered orally to maintain the blind.	Drug: Baricitinib; Administered orally.; Other Name: LY3009104; Drug: Placebo; Administered orally
Placebo Comparator: Placebo; Placebo administered orally.	Drug: Placebo; Administered orally

Outcome Measures

Primary Outcome Measures :

1. Percentage of Participants Achieving a Systemic Lupus Erythematosus Responder Index 4 (SRI-4) Response (High Dose) [ Time Frame: Week 52 ]
   Percentage of participants achieving SRI-4 response (high dose).

Secondary Outcome Measures :

1. Percentage of Participants Achieving SRI-4 Response (Low Dose) [ Time Frame: Week 52 ]
   Percentage of participants achieving SRI-4 response (low dose).
2. Percentage of Participants Achieving a Lupus Low Disease Activity State (LLDAS) [ Time Frame: Week 52 ]
   Percentage of Participants Achieving a LLDAS.
3. Time to First Severe Flare [ Time Frame: Baseline to Week 52 ]
   Time to first severe flare.
4. Change from Baseline in Prednisone Dose [ Time Frame: Baseline, Week 52 ]
   Change from baseline in prednisone dose.
5. Change from Baseline in Worst Pain Numeric Rating Scale (NRS) [ Time Frame: Baseline, Week 52 ]
   Change from baseline in worst pain NRS.
6. Change from Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Total Score [ Time Frame: Baseline, Week 52 ]
   Change from baseline on FACIT-Fatigue total score.
7. 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 52 ]
   Percentage of participants with CLASI total activity score ≥10 at baseline with ≥50% reduction in CLASI total activity score.
8. Change from Baseline in Tender Joint Count [ Time Frame: Baseline, Week 52 ]
   Change from baseline in tender joint count.
9. Change from Baseline in Swollen Joint Count [ Time Frame: Baseline, Week 52 ]
   Change from baseline in swollen joint count.
10. Population Pharmacokinetics (PK): Area Under the Concentration-Time Curve of Baricitinib at Steady State (AUCτ, ss) [ Time Frame: Baseline through Week 16 ]
    PK: Area Under the Concentration-Time Curve of Baricitinib at Steady State (AUCτ, ss).
11. Population PK: Maximum Observed Drug Concentration at Steady State (Cmax,ss) [ Time Frame: Baseline through Week 16 ]
    Population PK: Maximum Observed Drug Concentration at Steady State (Cmax,ss).

Eligibility Criteria

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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 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.

Contacts and Locations

Contacts

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Contact: There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or	1-317-615-4559	clinicaltrials.gov@lilly.com

  Show 134 Study Locations

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

More Information

Additional Information:

A Study of Baricitinib in Participants With Systemic Lupus Erythematosus 

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Responsible Party:	Eli Lilly and Company
ClinicalTrials.gov Identifier:	NCT03616964 History of Changes
Other Study ID Numbers:	16677; I4V-MC-JAIA ( Other Identifier: Eli Lilly and Company ); 2017-005027-25 ( EudraCT Number )
First Posted:	August 6, 2018
Last Update Posted:	March 19, 2019
Last Verified:	March 1, 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	Yes
Plan Description:	Lilly provides access to the individual patient data from studies on approved medicines and indications as defined by the sponsor specific information on ClinicalStudyDataRequest.com This access is provided in a timely fashion after the primary publication is accepted. Researchers need to have an approved research proposal submitted through ClinicalStudyDataRequest.com. Access to the data will be provided in a secure data sharing environment after signing a data sharing agreement.

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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