A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Phase 3 Study of Baricitinib in Patients with Systemic Lupus Erythematosus.

[1] Are at least 18 years of age., [2] Have a clinical diagnosis of SLE at
least 24 weeks prior to screening., [3] 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 ACR criteria for
classification of SLE (Tan et al. 1982; Hochberg et al. 1997) prior to
randomization., [4] Have 1 or more of the following as assessed by the central
lab during screening: a positive antinuclear antibody (ANA; titer >=1:80),
and/or a positive anti-dsDNA, and/or a positive anti-Smith (anti-Sm). Patients
with an ANA <1:80 at screening with documentation of a historical ANA >=1:80 may
be eligible, as assessed by the eligibility review committee., Note: The ANA,
anti-dsDNA, and anti-Smith measurements may be repeated by the central lab once
during the screening period, and the value resulting from repeat testing may be
accepted for enrollment eligibility if it meets the eligibility criterion., [5]
Have a total SLEDAI-2K score >=6 during screening, with at least 4 points
attributed to clinical items (not including items requiring laboratory value
assessment). SLEDAI-2K items requiring laboratory values should be assessed
based on the results from the labs drawn during the screening period., [6] Have
a clinical SLEDAI-2K score >=4 at Baseline (Visit 2); not including any items
requiring laboratory value assessment., [7] Have at least 1 BILAG A score or 2
BILAG B scores during the screening period. BILAG items requiring laboratory
values should be assessed based on the results from the labs drawn during the
screening period., Prior/Concomitant Therapy
[8] Are receiving at least one of the following SoC medications for SLE:, a. A
single antimalarial (such as hydroxychloroquine, chloroquine, quinacrine) at a
stable therapeutic dose for at least 8 weeks prior to screening (Visit 1)., b.
A single immunosuppressant (such as methotrexate [MTX], azathioprine,
mycophenolate, tacrolimus) at a stable therapeutic dose for at least 8 weeks
prior to screening (Visit 1)., c. An oral corticosteroid, initiated at least 4
weeks prior to screening (Visit 1), at a stable dose <= 40 mg/day prednisone (or
equivalent) for at least 2 weeks prior to screening (Visit 1) and through
baseline (Visit 2). If the patient is not receiving an antimalarial or
immunosuppressant, the dose of corticosteroid must be >= 7.5 mg/day prednisone
(or equivalent)., Patient Characteristics
[9] Male or nonpregnant, nonbreastfeeding female patient, a. Patients of
child-bearing potential who are abstinent (if this is complete abstinence, as
their preferred and usual lifestyle) or in a same-sex relationship (as part of
their preferred and usual lifestyle) must agree to either remain abstinent or
stay in a same-sex relationship without sexual relationships with the opposite
sex., b. Total abstinence is defined as refraining from intercourse during the
entirety of the study and for at least 1 week following the last dose of
investigational product. Periodic abstinence such as calendar, ovulation,
symptothermal, post-ovulation methods and withdrawal are not acceptable methods
of contraception., c. Otherwise, patients of childbearing potential must agree
to use 2 effective methods of contraception, where at least 1 form is highly
effective, for the entirety of the study and for at least 1 week following the
last dose of investigational product., d. The following contraception methods
are considered acceptable (the patient should choose 2, and 1 must be highly
effective [defined as less than 1% failure rate per year when used consistently
and correctly]):
* Highly effective birth control methods:
* Combined (estrogen and progestogen containing) hormonal contraception
associated with inhibition of ovulation: oral,
intravaginal, or transdermal
* Progestogen- only containing hormonal contraception associated with
inhibition of ovulation: oral, intravaginal, or transdermal
* intrauterine device (IUD)/intrauterine hormone-releasing system (IUS)
* vasectomized male (with appropriate post-vasectomy documentation of the
absence of sperm in the ejaculate).
* Effective birth control methods:
* Male or female condom with spermicide. It should be noted that the use of
male and female condoms as a double barrier method is
not considered acceptable due to the high failure rate when these methods are
combined.
* Diaphragm with spermicide
* Cervical sponge
* Cervical cap with spermacide
Note: When local guidelines concerning highly effective or effective methods of
birth control differ from the above, the local guidelines must be followed.
Patients of non*child-bearing potential are not required to use birth control
and they are defined as:
* women who are infertile due to surgical sterilization (hysterectomy,
bilateral oophorectomy, or tubal ligation who has had either
* Cessation of menses for at least 1 year
* At least 6 months of spontaneous amenorrhea with follicle-stimulating hormone
>40 mIU/mL
* Women aged 55 years or older who are not on hormone therapy, and who have had
at least 6 months of spontaneous amenorrhea
* Women aged 55 years or older who have a diagnosis of menopause, Informed
Consent
[10] Must read and understand the informed consent approved by Eli Lilly and
Company (Lilly), or its designee, and the institutional review board
(IRB)/ethics review board (ERB) governing the site, and provide written
informed consent.

Medical Conditions
[1] Have severe active lupus nephritis defined clinically and/or by histologic
evidence of proliferative glomerulonephritis on renal biopsy (if available)
within the 24 weeks prior to screening, or urine protein/creatinine ratio >200
mg/mmol (as an estimate of approximate proteinuria >2 g/day) or eGFR
(Modification of Diet in Renal Disease [MDRD]) <40 mL/min/1.73 m2 at screening,
or as determined by
the eligibility review committee., Note: The lab measurements related to lupus
nephritis may be repeated once by the central lab during the screening period,
and the values resulting from repeat testing may be accepted for enrollment
eligibility if they meet the eligibility criterion.,
[2] Have active CNS lupus as defined by ACR nomenclature for neuropsychiatric
lupus syndromes and as captured by SLEDAI-2K (seizure, psychosis, organic brain
syndrome, visual disturbance, cranial nerve disorder, lupus headache, and
cerebrovascular accident).,
[3] Have active fibromyalgia that, in the investigator*s opinion, would make it
difficult to appropriately assess SLE activity for the purposes of this study.,
[4] Have been treated for or had an active occurrence of a systemic
inflammatory condition other than SLE such as, but not limited to, RA, juvenile
chronic arthritis, spondyloarthropathy, Crohn*s disease, ulcerative colitis, or
psoriatic arthritis within the 12 weeks prior to screening. Patients with
secondary Sjögren*s syndrome are not excluded.,
[5] Have had any major surgery within 8 weeks prior to screening or will
require major surgery during the study that, in the opinion of the investigator
in
consultation with Lilly or its designee, would pose an unacceptable risk to the
patient.,
[6] Have screening electrocardiogram (ECG) abnormalities that, in the opinion
of the investigator, are clinically significant and indicate an unacceptable
risk for the patient*s participation in the study.,
[7] Have experienced any of the following within 12 weeks of screening: VTE
(DVT/pulmonary embolism [PE]), myocardial infarction (MI), unstable ischemic
heart disease, stroke, or New York Heart Association Stage III/IV heart
failure.,
[8] Have a history of recurrent (>= 2) VTE (DVT/PE).,
[9] 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.,
[10] Have a history of lymphoproliferative disease; have signs or symptoms
suggestive of possible lymphoproliferative disease, including
lymphadenopathy or splenomegaly (other than primarily due to SLE); have active
primary or recurrent malignant disease; or have been in remission from
clinically significant malignancy for <5 years prior to randomization. The
following may be exempted:
a. Patients with cervical carcinoma in situ that has been resected with no
evidence of recurrence or metastatic disease for at least 3 years may
participate in the study.
b. Patients with basal cell or squamous epithelial skin cancers that have been
completely resected with no evidence of recurrence for at least 3 years may
participate in the study., [11] Have a current or recent (<4 weeks prior to
randomization) clinically serious viral, bacterial, fungal, or parasitic
infection or any other active or recent infection that in the opinion of the
investigator, would pose an unacceptable risk to the patient if participating
in the study. Note: For example, a recent viral upper respiratory tract
infection or uncomplicated urinary tract infection need not be considered
clinically serious., [12] Have symptomatic herpes simplex at the time of
randomization., [13] Have had symptomatic herpes zoster infection within 12
weeks prior to randomization., [14] Have a history of disseminated/complicated
herpes zoster (for example, multidermatomal involvement, ophthalmic zoster, CNS
involvement, or
post-herpetic neuralgia)., [15] Have a positive test for hepatitis B virus
(HBV) defined as:
a. positive for hepatitis B surface antigen (HBsAg), or
b. positive for hepatitis B core antibody (HBcAb) and positive for hepatitis B
virus deoxyribonucleic acid (HBV DNA)
Note: Patients who are HBcAb-positive and HBV DNA-negative may be enrolled in
the study but will require additional HBV DNA monitoring during
the study., [16] Have hepatitis C virus (HCV) infection (hepatitis C
antibody-positive and HCV ribonucleic acid [RNA]-positive).
Note: Patients who have documented anti-HCV treatment for a past HCV infection
AND are HCV RNA-negative may be enrolled in the study., [17] Have evidence of
HIV infection and/or positive HIV antibodies., [18] Have had household contact
with a person with active TB and did not receive appropriate and documented
prophylaxis for TB., [19] Have evidence of active TB or latent TB
a. Have evidence of active TB, defined in this study as the following:
* Positive purified protein derivative (PPD) test (>=5 mm induration between
approximately 2 and 3 days after application, regardless of vaccination
history), medical history, clinical features, and abnormal chest x-ray at
screening.
* QuantiFERON®-TB Gold test or T-SPOT®.TB test (as available and if compliant
with local TB guidelines) may be used instead of the PPD test. Patients are
excluded from the study if the test is not negative and there is clinical
evidence of active TB.
Exception: patients with a history of active TB who have documented evidence of
appropriate treatment, have no history of re-exposure since their treatment was
completed, have no clinical features of active TB, and have a screening chest
x-ray with no evidence of active TB may be enrolled if other entry criteria
met. Such patients would not be required to undergo the protocol-specific TB
testing for PPD, QuantiFERON®-TB Gold test, or T-SPOT®.TB test but must have a
chest x-ray at screening (i.e., a chest x-ray performed within the past 6
months will not be accepted)., b. Have evidence of untreated/inadequately or
inappropriately treated latent TB, defined in this study as the following:
* Positive PPD test, no clinical features consistent with active TB, and a
chest x-ray with no evidence of active TB at screening; or
* If the PPD test is positive and the patient has no medical history or chest
x-ray findings consistent with active TB, the patient may have a
QuantiFERON®-TB Gold test or T-SPOT®.TB test (as available and if compliant
with local TB guidelines). If the test results are not negative, the patient
will be considered to have latent TB (for purposes of this study); or
* QuantiFERON®-TB Gold test or T- SPOT®.TB test (as available and if compliant
with local TB guidelines) may be used instead of the PPD test.
If the test results are positive, the patient will be considered to have latent
TB. If the test is not negative, the test may be repeated once within
approximately 2 weeks of the initial value. If the repeat test results are
again not negative, the patient will be considered to have latent TB (for
purposes of this study).
Exception: Patients who have evidence of latent TB may be enrolled if he or she
completes at least 4 weeks of appropriate treatment prior to
randomization and agrees to complete the remainder of treatment while in the
trial.
Exception: Patients with a history of latent TB who have documented evidence of
appropriate treatment, have no history of re-exposure since their
treatment was completed, have no clinical features of active TB, and have a
screening chest x-ray with no evidence of active TB may be enrolled if other
entry criteria met. Such patients would not be required to undergo the
protocol-specific TB testing for PPD, QuantiFERON®-TB Gold test, or T-SPOT®.TB
test but must have a chest x-ray