Moderate to Severe Atopic Dermatitis

Primary To test the hypothesis that baricitinib 4-mg QD is superior to placebo in the treatment of patients with moderate to severe AD. Key Secondary (These are prespecified objectives that will be adjusted for multiplicity) -To test the hypothesis that baricitinib 2-mg QD or baricitinib 1-mg QD is superior to placebo in the treatment of patients with moderate to severe AD. -To compare the efficacy of baricitinib 1-mg QD, 2-mg QD, or 4-mg QD to placebo in AD during the 16-week double-blind placebo-controlled treatment period as measured by improvement in signs and symptoms of AD. -To compare the efficacy of baricitinib 1-mg QD, 2-mg QD, or 4-mg QD to placebo in AD during the 16-week double-blind placebo-controlled treatment period as assessed by patient-reported outcome measures.

Baricitinib (LY3009104)

Baricitinib (LY3009104)

Tablet

1 mg, 2 mg and 4 mg

Primary Outcome Measures :
Percentage of Participants Achieving Investigator's Global Assessment (IGA) of 0 or 1 With a ≥ 2 Point Improvement (Placebo, 2 mg, or 4 mg Baricitinib) [ Time Frame: 16 Weeks ]
The IGA measures the investigator's global assessment of the participant's overall severity of their atopic dermatitis (AD), based on a static, numeric 5-point scale from 0 (clear skin) to 4 (severe disease). The score is based on an overall assessment of the degree of erythema, papulation/induration, oozing/crusting, and lichenification.


Secondary Outcome Measures :
Percentage of Participants Achieving IGA of 0 or 1 With a ≥ 2 Point Improvement (Placebo, 1 mg Baricitinib) [ Time Frame: 16 Weeks ]
The IGA measures the investigator's global assessment of the participant's overall severity of their AD, based on a static, numeric 5-point scale from 0 (clear skin) to 4 (severe disease). The score is based on an overall assessment of the degree of erythema, papulation/induration, oozing/crusting, and lichenification.

Percentage of Participants Achieving Eczema Area and Severity Index 75 (EASI75) [ Time Frame: 16 Weeks ]
The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent and clinical signs affected: 0 = 0%; 1 = 1-9%; 2 = 10-29%; 3 = 30-49%; 4 = 50-69%; 5 = 70-89%; 6 = 90-100% and the severity of 4 clinical signs: (1) erythema, (2) edema/papulation, (3) excoriation, and (4) lichenification each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe) at 4 body sites (head/neck, trunk, upper limbs, and lower limbs). Half scores are allowed between severities 1, 2, and 3. The final EASI score was obtained by weight-averaging these 4 scores and will range from 0 to 72 (severe). The EASI75 is defined as a ≥ 75% improvement from baseline in the EASI score.

Percentage of Participants Achieving EASI90 [ Time Frame: 16 Weeks ]
The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent and clinical signs affected: 0 = 0%; 1 = 1-9%; 2 = 10-29%; 3 = 30-49%; 4 = 50-69%; 5 = 70-89%; 6 = 90-100% and the severity of 4 clinical signs: (1) erythema, (2) edema/papulation, (3) excoriation, and (4) lichenification each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe) at 4 body sites (head/neck, trunk, upper limbs, and lower limbs). Half scores are allowed between severities 1, 2, and 3. The final EASI score was obtained by weight-averaging these 4 scores and will range from 0 to 72 (severe). The EASI90 is defined as a ≥ 90% improvement from baseline in the EASI score.

Percent Change From Baseline in EASI Score [ Time Frame: Baseline, 16 Weeks ]
The EASI assesses objective physician estimates of 2 dimensions of AD - disease extent and clinical signs affected: 0 = 0%; 1 = 1-9%; 2 = 10-29%; 3 = 30-49%; 4 = 50-69%; 5 = 70-89%; 6 = 90-100% and the severity of 4 clinical signs: (1) erythema, (2) edema/papulation, (3) excoriation, and (4) lichenification each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe) at 4 body sites (head/neck, trunk, upper limbs, and lower limbs). Half scores are allowed between severities 1, 2, and 3. The final EASI score was obtained by weight-averaging these 4 scores and will range from 0 to 72 (severe).

Least Square (LS) Means were calculated using a MMRM model with treatment, region, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-visit-interaction as fixed continuous effect


Percentage of Participants Achieving SCORing Atopic Dermatitis 75 (SCORAD75) [ Time Frame: 16 Weeks ]
The SCORAD index uses the rule of nines to assess disease extent and evaluates 6 clinical characteristics to determine disease severity: (1) erythema, (2) edema/papulation, (3) oozing/crusts, (4) excoriation, (5) lichenification, and (6) dryness on a scale of 0 to 3 (0=absence, 1=mild, 2=moderate, 3=severe). The SCORAD index also assesses subjective symptoms of pruritus and sleep loss with visual analog scale (VAS) where 0 is no itching or no trouble sleeping and 10 is unbearable itching or a lot of trouble sleeping. These 3 aspects: extent of disease (A: 0-1-2), disease severity (B: 0-18), & subjective symptoms (C: 0-20) combine using A/5 + 7*B/2+ C to give a maximum possible score of 103, where 0 = no disease and 103 = severe disease. The SCORAD75 responder is defined as a participant who achieves a ≥ 75% improvement from baseline in the SCORAD score.

Percentage of Participants Achieving a 4-Point Improvement in Itch Numeric Rating Scale (NRS) [ Time Frame: 16 Weeks ]
The Itch Numeric Rating Scale (NRS) is a participant-administered, 11-point horizontal scale anchored at 0 and 10, with 0 representing "no itch" and 10 representing "worst itch imaginable." Overall severity of a participants itching is indicated by selecting the number, using a daily diary, that best describes the worst level of itching in the past 24 hours.

Change From Baseline in the Score of Item 2 of the Atopic Dermatitis Sleep Scale (ADSS) [ Time Frame: Baseline, 16 Weeks ]
Atopic Dermatitis Sleep Scale (ADSS) is a 3-item, participant-administered questionnaire developed to assess the impact of itch on sleep including difficulty falling asleep, frequency of waking, and difficulty getting back to sleep last night. Item 2, frequency of waking last night is reported by selecting the number of times they woke up each night, ranging from 0 to 29 times,where the higher a number indicates a worse outcome. The ADSS is designed to be completed daily, using a daily diary, with respondents thinking about sleep "last night." Each item is scored individually.

LS Means were calculated using a MMRM model with treatment, region, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by- visit-interaction as fixed continuous effects.


Change From Baseline in the Skin Pain Numeric Rating Scale (NRS) [ Time Frame: Baseline, 16 Weeks ]
Skin Pain NRS is a participant-administered, 11-point horizontal scale anchored at 0 and 10, with 0 representing "no pain" and 10 representing "worst pain imaginable." Overall severity of a participant's skin pain is indicated by selecting the number, using a daily diary, that best describes the worst level of skin pain in the past 24 hours.

LS Means were calculated using a MMRM model with treatment, region, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-visit-interaction as fixed continuous effects.


Percentage of Participants Achieving EASI50 [ Time Frame: 16 Weeks ]
The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent and clinical signs affected: 0 = 0%; 1 = 1-9%; 2 = 10-29%; 3 = 30-49%; 4 = 50-69%; 5 = 70-89%; 6 = 90-100%) and the severity of 4 clinical signs (erythema, edema/papulation, excoriation, and lichenification) each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe) at 4 body sites (head and neck, trunk, upper limbs, and lower limbs). Half scores are allowed between severities 1, 2 and 3. The final EASI score was obtained by weight-averaging these 4 scores and will range from 0 to 72 (severe). The EASI50 is defined as a ≥ 50% improvement from baseline in EASI score.

Percentage of Participants Achieving IGA of 0 [ Time Frame: 16 Weeks ]
The IGA measures the investigator's global assessment of the participant's overall severity of their AD, based on a static, numeric 5-point scale from 0 (clear skin) to 4 (severe disease). The score is based on an overall assessment of the degree of erythema, papulation/induration, oozing/crusting, and lichenification.

Change From Baseline in SCORAD [ Time Frame: Baseline, 16 Weeks ]
The SCORAD index uses the rule of nines to assess disease extent and evaluates 6 clinical characteristics to determine disease severity: (1) erythema, (2) edema/papulation, (3) oozing/crusts, (4) excoriation, (5) lichenification, and (6) dryness on a scale of 0 to 3 (0=absence, 1=mild, 2=moderate, 3=severe). The SCORAD index also assesses subjective symptoms of pruritus and sleep loss with VAS where 0 is no itching or no trouble sleeping and 10 is unbearable itching or a lot of trouble sleeping. These 3 aspects: extent of disease (A: 0-1-2), disease severity (B: 0-18), & subjective symptoms (C: 0-20) combine using A/5 + 7*B/2+ C to give a maximum possible score of 103, where 0 = no disease and 103 = severe disease.

LS Means were calculated using a MMRM model with treatment, region, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-visit-interaction as fixed continuous effects.


Percentage of Participants Achieving SCORAD90 [ Time Frame: 16 Weeks ]
The SCORAD index uses the rule of nines to assess disease extent and evaluates 6 clinical characteristics to determine disease severity: (1) erythema, (2) edema/papulation, (3) oozing/crusts, (4) excoriation, (5) lichenification, and (6) dryness on a scale of 0 to 3 (0=absence, 1=mild, 2=moderate, 3=severe). The SCORAD index also assesses subjective symptoms of pruritus and sleep loss with VAS where 0 is no itching or no trouble sleeping and 10 is unbearable itching or a lot of trouble sleeping. These 3 aspects: extent of disease (A: 0-1-2), disease severity (B: 0-18), & subjective symptoms (C: 0-20) combine using A/5 + 7*B/2+ C to give a maximum possible score of 103, where 0 = no disease and 103 = severe disease. SCORAD90 is defined as a ≥ 90% improvement from baseline in the SCORAD score.

Change From Baseline in Body Surface Area (BSA) Affected [ Time Frame: Baseline, 16 Weeks ]
Body surface area affected by AD will be assessed for 4 separate body regions and is collected as part of the EASI assessment: head and neck, trunk (including genital region), upper extremities, and lower extremities (including the buttocks). Each body region will be assessed for disease extent ranging from 0% to 100% involvement. The overall total percentage will be reported based off of all 4 body regions combined, after applying specific multipliers to the different body regions to account for the percent of the total BSA represented by each of the 4 regions. Use the percentage of skin affected for each region (0 to 100%) in EASI as follows: BSA Total = 0.1*BSAhead and neck + 0.3*BSAtrunk + 0.2* BSAupper limbs + 0.4*BSAlower limbs.

LS Means were calculated using MMRM model with treatment, region, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-visit-interaction as fixed continuous effects.


Percentage of Participants Developing Skin Infections Requiring Antibiotic Treatment [ Time Frame: 16 Weeks ]
Percentage of participants developing skin infections requiring antibiotic treatment.

Percent Change From Baseline in Itch NRS [ Time Frame: Baseline, 16 Weeks ]
The Itch NRS is a participant-administered, 11-point horizontal scale, with 0 representing "no itch" and 10 representing "worst itch imaginable." Overall severity of a participant's itching is indicated by selecting the number, using a daily diary, that best describes the worst level of itching in the past 24 hours.

LS Means were calculated using a MMRM model with treatment, region, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-visit-interaction as fixed continuous effects.


Change From Baseline in the Total Score of the Patient Oriented Eczema Measure (POEM) [ Time Frame: Baseline, 16 Weeks ]
The POEM is a 7-item self-assessment questionnaire that assesses disease symptoms (dryness, itching, flaking, cracking, sleep loss, bleeding and weeping) on a scale ranging from 0-4 (0 = no days, 1 = 1-2 days, 2 = 3-4 days, 3 = 5-6 days, 4 = everyday). The sum of the 7 items gives the total POEM score of 0 (absent disease) to 28 (severe disease). High scores are indicative of more severe disease and poor quality of life.

LS Means were calculated using a MMRM model with treatment, region, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-visit-interaction as fixed continuous effects.


Change From Baseline in the Patient Global Impression of Severity-Atopic Dermatitis (PGI-S-AD) Score [ Time Frame: Baseline, 16 Weeks ]
The PGI-S-AD asked the participant to evaluate the severity of the disease at that point in time on a single-item, 5-point scale, using a daily diary. The same category labels used in the Physician's Global Assessment were used for the PGI-S-AD, i.e., "(0) no symptoms", "(1) very mild", "(2) mild" "(3) moderate", and "(4) severe."

LS Means were calculated using a MMRM model with treatment, region, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-visit-interaction as fixed continuous effects.


Change From Baseline on the Hospital Anxiety and Depression Scale (HADS) [ Time Frame: Baseline, 16 Weeks ]
The HADS is a participant-rated instrument used to assess both anxiety and depression. This instrument consists of 14 item questionnaire, each item is rated on a 4-point scale, giving maximum scores of 21 for anxiety and depression. Scores of 11 or more on either subscale are considered to be a significant 'case' of psychological morbidity, while scores of 8-10 represent 'borderline' and 0-7, 'normal.' LS Means were calculated using a MMRM model with treatment, region, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-visit-interaction as fixed continuous effects.

Change From Baseline in the Dermatology Life Quality Index (DLQI) [ Time Frame: Baseline, 16 Weeks ]
The DLQI is a simple, participant-administered,10 question, validated, quality-of-life questionnaire that covers 6 domains including symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment. The recall period of this scale is over the last "week." Response categories include "not at all," "a lot," and "very much," with corresponding scores of 1, 2, and 3, respectively, and at unanswered ("not relevant") responses scored as "0." Scores range from 0 to 30 (less to more impairment), and a 4-point change from baseline is considered as the minimal clinically important difference threshold.

LS Means were calculated using a MMRM model with treatment, region, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-visit-interaction as fixed continuous effects.


Change From Baseline on the Work Productivity and Activity Impairment - Atopic Dermatitis (WPAI-AD) Questionnaire [ Time Frame: Baseline, 16 Weeks ]
The WPAI-AD participant questionnaire was developed to measure the effect of general health and symptom severity on work productivity and regular activities in the 7 days prior to the visit. The WPAI-AD consists of 6 items grouped in 4 domains: absenteeism (work time missed), presenteeism (impairment at work/reduced on-the-job effectiveness), work productivity loss (overall work impairment/absenteeism plus presenteeism), and activity impairment, that range from 0% to 100%, with higher values indicating greater impairment.

LS Means were calculated using a MMRM model with treatment, region, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-visit-interaction as fixed continuous effects.


Change From Baseline on the European Quality of Life-5 Dimensions 5 Levels (EQ-5D-5L) Index Score United States and United Kingdom Algorithm [ Time Frame: Baseline, 16 Weeks ]
EQ-5D-5L is a 2-part measurement. The first part is comprised of the following 5 participant-reported dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The responses are used to derive the health state index scores using the United Kingdom (UK) algorithm, with scores ranging from -0.594 to 1, and the United States (US) algorithm, with scores ranging from -0.109 to 1, with higher score indicating better health state.

LS Means were calculated using MMRM model with treatment, region, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-visit-interaction as fixed continuous effects.


Change From Baseline on the European Quality of Life-5 Dimensions 5 Levels (EQ-5D-5L) Visual Analog Score (VAS) [ Time Frame: Baseline, 16 Weeks ]
EQ-5D-5L is a 2-part measurement. The second part is assessed using a visual analog scale (VAS) that ranged from 0 to 100 millimeter (mm), where 0 is the worst health you can imagine and 100 is the best health you can imagine.

LS Means were calculated using MMRM model with treatment, region, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-visit-interaction as fixed continuous effects.


Percentage of Participants Achieving Investigator's Global Assessment (IGA) of 0 or 1 With a ≥ 2 Point Improvement [ Time Frame: 4 Weeks ]
The IGA measures the investigator's global assessment of the participant's overall severity of their AD, based on a static, numeric 5-point scale from 0 (clear skin) to 4 (severe disease). The score is based on an overall assessment of the degree of erythema, papulation/induration, oozing/crusting, and lichenification.

Inclusion Criteria
Informed Consent
[1] are at least 18 years of age at the time of informed consent.
Note: Use local requirements to provide consent if the age of adulthood is
defined as >18 years
[2] are able to read, understand, and give documented (electronic or paper
signature) informed consent.
Type of Patient and Disease Characteristics
[3] have a diagnosis of AD at least 12 months prior to screening, as defined by the
American Academy of Dermatology: Guidelines of care for the management
of AD; Section 1. Diagnosis and assessment of atopic dermatitis (see
Appendix 6).
[4] have moderate to severe AD, including all of the following:
a. Eczema Area and Severity Index (EASI) score ≥16 at screening (Visit 1)
and at randomization (Visit 2)
b. IGA score of ≥3 at screening (Visit 1) and at randomization (Visit 2)
c. ≥10% of BSA involvement at screening (Visit 1) and at randomization
(Visit 2).
[5] have a documented history by a physician and/or investigator of inadequate
response to existing topical medications within 6 months preceding screening,
or history of intolerance to topical therapy as defined by at least 1 of the
following:
a. inability to achieve good disease control defined as mild disease or better
(e.g., IGA ≤2) after use of at least a medium potency TCS for at least
4 weeks, or for the maximum duration recommended by the product
prescribing information (e.g., 14 days for super-potent TCS), whichever
is shorter. Topical corticosteroids may be used with or without TCNIs.
b. Patients who failed systemic therapies intended to treat AD within
6 months preceding screening, such as cyclosporine, methotrexate,
azathioprine, mycophenolate mofetil will also be considered as a
surrogate for having inadequate response to topical therapy.
c. documented history of clinically significant adverse reactions with the use
of TCS such as skin atrophy, allergic reactions, systemic effects that in
the opinion of the investigator outweigh the benefits of retreatment.
[6] agree to discontinue use of the following excluded medications/treatments for
at least 4 weeks prior to randomization (Visit 2) and throughout the study:
a. systemic corticosteroids and leukotriene inhibitors
b. systemic immunomodulators, including, but not limited to, cyclosporine,
methotrexate, mycophenolate mofetil, and azathioprine
c. sedating antihistamines, including, but not limited to, alimemazine,
chlorphenamine, clemastine, cyproheptadine, diphenhydramine,
hydroxyzine, ketotifen, and promethazine
Note: Patients may use newer, less sedating antihistamines (e.g.,
fexofenadine, loratadine, cetirizine).
d. any other systemic therapy used to treat AD or symptoms of AD
(approved or off-label use)
e. phototherapy, includes therapeutic phototherapy (psoralen plus
ultraviolet-A, ultraviolet-B), excimer laser as well as self-treatment with
tanning beds.
[7] agree to discontinue use of the following excluded medications for at least
2 weeks prior to randomization (Visit 2) and throughout the study:
a. TCS or topical immune modulators (e.g., tacrolimus or pimecrolimus)
b. Topical phosphodiesterase type 4 (PDE-4) inhibitor (crisaborole)
c. Topical JAK inhibitor (e.g., tofacitinib or ruxolitinib) and/or any other
investigative topical treatments.
[8] have applied emollients daily for at least 14 days prior to randomization and
agree to use emollient daily throughout the treatment period.
[9] Patients who are receiving chronic treatments to improve sleep should be on a
stable dose for at least 2 weeks prior to screening as determined by the
investigator. Sedating antihistamines (see above) are not permitted.
Patient Characteristics
[10] are male or nonpregnant, nonbreastfeeding female patients, except
a. Male patients must agree to use 2 forms of birth control (1 must be highly
effective, see below) while engaging in sexual intercourse with female
partners of childbearing potential while enrolled in the study and for at
least 4 weeks following the last dose of investigational product.
b. Female patients of childbearing potential must agree to use 2 forms of
birth control, when engaging in sexual intercourse with a male partner
while enrolled in the study and for at least 4 weeks following the last dose
of investigational product.
The following birth control methods are considered acceptable (the patient should choose 2 to be
used with their male partner, and 1 must be highly effective):
o highly effective birth control methods: oral, injectable, or implanted hormonal
contraceptives (combined estrogen/progesterone or progesterone only, associated
with inhibition of ovulation); intrauterine device or intrauterine system (e.g.,
progestin-releasing coil); or vasectomized male (with appropriate post-vasectomy
documentation of the absence of sperm in the ejaculate).
o effective birth control methods: condom with a spermicidal foam, gel, film,
cream, or suppository; occlusive cap (diaphragm or cervical/vault caps) with a
spermicidal foam, gel, film, cream, or suppository; or oral hormonal
contraceptives.
Note: When local guidelines concerning highly effective or effective methods of birth control
differ from the above, the local guidelines must be followed.
c. Females of nonchildbearing potential are not required to use birth control
and they are defined as:
o women ≥60 years of age or women who are congenitally sterile, or
o women ≥40 and <60 years of age who have had a cessation of menses for
≥12 months and a follicle-stimulating hormone (FSH) test confirming
nonchildbearing potential (≥40 mIU/mL or ≥40 IU/L), or women who are
surgically sterile (i.e., have had a hysterectomy or bilateral oophorectomy
or tubal ligation).

Exclusion Criteria
Patients will be excluded from study enrollment if they meet any of the following criteria:
Medical Conditions Related to Atopic Dermatitis
[11] are currently experiencing or have a history of other concomitant skin
conditions (e.g., psoriasis or lupus erythematosus) that would interfere with
evaluations of the effect of study medication on AD.
[12] patients who, in the opinion of the investigator, are currently experiencing or
have a history of erythrodermic, refractory, or unstable skin disease that
requires frequent hospitalizations and/or intravenous treatment for skin
infections that may interfere with participation in the study.
[13] a history of eczema herpeticum within 12 months prior to screening.
[14] a history of 2 or more episodes of eczema herpeticum in the past.
[15] patients who are currently experiencing a skin infection that requires
treatment, or is currently being treated, with topical or systemic antibiotics.
Note: Patients may not be rescreened until at least 4 weeks after the date of
their previous screen failure and at least 2 weeks after resolution of the
infection.
[16] have any serious concomitant illness that is anticipated to require the use of
systemic corticosteroids or otherwise interfere with study participation or
require active frequent monitoring (e.g., unstable chronic asthma).
[17] have been treated with the following therapies:
a. monoclonal antibody (e.g., ustekinumab, omalizumab, dupilumab) for
less than 5 half-lives prior to randomization.
b. received prior treatment with any oral JAK inhibitor (e.g., tofacitinib,
ruxolitinib)
c. received any parenteral corticosteroid administered by intramuscular or
intravenous injection within 2 weeks prior to study entry (Visit 1) or
within 6 weeks prior to planned randomization (Visit 2) or are anticipated
to require parenteral injection of corticosteroids during the study.
d. have had an intra-articular corticosteroid injection within 2 weeks prior to
study entry (Visit 1) or within 6 weeks prior to planned randomization
(Visit 2).
Note: Intranasal or inhaled steroid use is allowed during the trial.
Medical Conditions in General
[18] are largely or wholly incapacitated permitting little or no self-care, such as
being bedridden.
[19] have uncontrolled arterial hypertension characterized by a repeated systolic
blood pressure >160 mm Hg or diastolic blood pressure >100 mm Hg in a
seated position.
[20] 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.
[21] are immunocompromised and, in the opinion of the investigator, at an
unacceptable risk for participating in the study.
[22] have experienced any of the following within 12 weeks of screening: venous
thromboembolic event (VTE), myocardial infarction (MI), unstable ischemic
heart disease, stroke, or New York Heart Association Stage III/IV heart
failure.
[23] have a history of recurrent (≥ 2) VTE or are considered at high risk of VTE as
deemed by the investigator.
[24] 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.
[25] have a history of lymphoproliferative disease; or have signs or symptoms
suggestive of possible lymphoproliferative disease, including
lymphadenopathy or splenomegaly; or have active primary or recurrent
malignant disease; or have been in remission from clinically significant
malignancy for less than 5 years.
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.
[26] have a current or recent clinically serious viral, bacterial, fungal, or parasitic
infection, including but not limited to the following:
Note: A recent viral upper respiratory tract infection or uncomplicated
urinary tract infection should not be considered clinically serious.
a. symptomatic herpes zoster infection within 12 weeks prior to screening.
b. a history of disseminated/complicated herpes zoster (e.g.,
multidermatomal involvement, ophthalmic zoster, CNS involvement, or
post-herpetic neuralgia).
c. symptomatic herpes simplex at the time of randomization.
d. active or chronic viral infection from hepatitis B virus (HBV), hepatitis C
virus (HCV), or human immunodeficiency virus (HIV).
e. household contact with a person with active tuberculosis (TB) and did not
receive appropriate and documented prophylaxis for TB.
f. evidence of active TB or have previously had evidence of active TB and
did not receive appropriate and documented treatment.
g. clinically serious infection or received intravenous antibiotics for an
infection, within the past 4 weeks of randomization.
h. any other active or recent infection within 4 weeks of randomization that,
in the opinion of the investigator, would pose an unacceptable risk to the
patient if participating in the study.
[27] have been exposed to a live vaccine within 12 weeks prior to planned
randomization or are expected to need/receive a live vaccine during the course
of the study (with the exception of herpes zoster vaccination).
Note: Patients eligible for herpes zoster vaccine, who have not received it
prior to screening will be encouraged (per local guidelines) to do so prior to
randomization; vaccination must occur >4 weeks prior to randomization and
start of investigational product. Patients will be excluded if they were
exposed to herpes zoster vaccination within 4 weeks of planned
randomization. Investigators should review the vaccination status of their
patients and follow the local guidelines for vaccination of those ≥18 years of
age with nonlive vaccines intended to prevent infectious disease prior to
entering patients into the study.
[28] have a history of chronic alcohol abuse, IV drug abuse, or other illicit drug
abuse within the 2 years prior to screening.
[29] presence of significant uncontrolled neuropsychiatric disorder, are clinically
judged by the investigator to be at risk for suicide, or have a “yes” answer to
any of the following:
a. Question 4 (Active Suicidal Ideation with Some Intent to Act, Without
Specific Plan) on the “Suicidal Ideation” portion of the Columbia Suicide
Severity Rating Scale (C-SSRS) or
b. Question 5 (Active Suicidal Ideation with Specific Plan and Intent) on the
“Suicidal Ideation” portion of the C-SSRS or
c. Any of the suicide-related behaviors (actual attempt, interrupted attempt,
aborted attempt, preparatory act or behavior) on the “Suicidal Behavior”
portion of the C-SSRS;
and the ideation or behavior occurred within 2 months prior to Visit 1.
Note: a patient does not necessarily have to be excluded if they have
self-injurious behavior that would be classified as nonsuicidal self-injurious
behavior. If this situation arises, the subject should be referred to a
psychiatrist or appropriately trained professional as indicated.
[30] have donated more than a single unit of blood within 4 weeks prior to
screening or intend to donate blood during the course of the study.
Other Exclusions
[31] are unable or unwilling to make themselves available for the duration of the
study and/or are unwilling to follow study restrictions/procedures, including
use of data collection devices.
[32] are currently enrolled in any other clinical trial involving an investigational
product or any other type of medical research judged not to be scientifically or
medically compatible with this study.
[33] have participated within the last 30 days in a clinical study involving an
investigational product. If the previous investigational product has a long
half-life (2 weeks or longer), at least 3 months or 5 half-lives (whichever is
longer) should have passed.
[34] have previously been randomized in this study or any other study
investigating baricitinib.
[35] are investigator site personnel directly affiliated with this study and/or their
immediate families. Immediate family is defined as a spouse, parent, child, or
sibling, whether biological or legally adopted.
[36] are Lilly or Incyte employees or their designee