Alopecia Areata

Primary Objective To test the hypothesis that the high dose or low dose a of baricitinib is superior to placebo in the treatment of patients with severe or very severe AA Key Secondary Objectives (Double–Blind, Placebo-Controlled Treatment Period) -To compare the efficacy of baricitinib high dose or low dose a to placebo in AA during the double-blind, placebo-controlled treatment period as measured by physician-assessed signs and symptoms of AA -To compare the efficacy of baricitinib high dose or low dose a to placebo in AA during the double-blind, placebo-controlled treatment period as assessed by a PRO measure

Baricitinib (LY3009104)Baricitinib (LY3009104)Baricitinib (LY3009104)

Baricitinib (LY3009104)

Tablet
Tablet

2MG
4MG

Primary Outcome Measures :
Percentage of Participants Achieving Severity of Alopecia Tool (SALT) ≤ 20 [ Time Frame: Week 36 ]
Percentage of Participants Achieving SALT ≤ 20

[1] Are at least 18 years and ≤60 years for males (≤70 years of age for females) at
the time of informed consent.
Note: Use local requirements to provide consent if the age of adulthood is
defined as >18 years. Different upper age limits have been included for male
and female patients, based on difference in the prevalence of concomitant
androgenetic alopecia.
[2] Are able to read, understand, and give documented (electronic or paper
signature) informed consent.
[3] Have severe or very severe AA, as determined by all of the following:
a. Current AA episode of more than 6 months’ duration and hair loss
encompassing ≥50% of the scalp, as measured by SALT (AA-IGA of 3 or
4) at Visit 1 AND Visit 2.
b. No spontaneous improvement (ie, no more than 10 point spontaneous
reduction in SALT) over the past 6 months.
c. Current episode of severe or very severe AA of less than 8 years.
Note: patients who have severe or very severe AA for ≥8 years may be
enrolled if episodes of regrowth, spontaneous or under treatment, have been
observed on the affected areas over the past 8 years.
[4] Agree not to use any AA treatments during the study, including, but not
limited to the following:
a. Systemic therapies (eg, methotrexate, cyclosporine, corticosteroids, JAK
inhibitors) and biologics (eg, monoclonal antibodies)
b. Intralesional corticosteroid injections
c. Topical therapies, including irritants and immunotherapies (eg,
diphenylcyclopropenone)
d. Phototherapy, including lasers
e. Platelet-rich plasma injection
f. HMG CoA reductase inhibitors or “Statins” (eg, simvastatin, simvastatin +
ezetimibe) for treatment of AA
g. Cryotherapy
Note: Treatment with bimatoprost ophthalmic solution for eyelashes may be
continued if the patient has been on a stable dose for 8 weeks prior to
randomization. Treatment with finasteride or oral or topical minoxidil may be
continued if the patient has been on a stable dose for 12 months and are anticipated
to continue on a stable dose up until Week 36.
[5] Are male or nonpregnant, nonbreastfeeding female patients
a. Male patients will either remain abstinent (if this is their preferred and usual
lifestyle) or 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 IP. Men who are in exclusively same sex
relationships (when it is their preferred and usual lifestyle) are not required
to use contraception.
b. Female 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 males. Periodic abstinence (eg, calendar, ovulation,
symptothermal, post-ovulation methods), declaration of abstinence just for
the duration of a trial, and vaginal withdrawal are not acceptable methods of
contraception.
Otherwise, female patients of childbearing potential must agree to use 2 forms of
birth control, when engaging in sexual intercourse with male partners while
enrolled in the study and for at least 4 weeks following the last dose of IP.
The following birth control methods are considered acceptable (the patient should
choose 2 to be used with their male partners, and 1 must be highly effective):
 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 (eg, progestin-releasing coil); or vasectomized male (with appropriate
post-vasectomy documentation of the absence of sperm in the ejaculate).
 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 that do not inhibit ovulation.
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.
They are defined as:
 women ≥60 years of age or women who are congenitally sterile, or
 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 (ie, have had a hysterectomy or bilateral oophorectomy or
tubal ligation).

[6] Primarily “diffuse” type of AA (characterized by diffuse hair shedding)
[7] Are currently experiencing other forms of alopecia, including but not limited
to: androgenetic alopecia (male pattern Grade IV or greater using
Hamilton-Norwood classification, or female pattern), trichotillomania, telogen
effluvium, or any other concomitant conditions (eg, tinea capitis, psoriasis,
lupus erythematosus, or secondary syphilis) that would interfere with
evaluations of the effect of study medication on AA.
[8] Patients who, in the opinion of the investigator, are currently experiencing or
have a history of unstable concomitant disease that requires frequent
hospitalizations and/or frequent use of systemic immunosuppressants that may
interfere with participation in the study.
[9] Have been treated with the following therapies:
a. Corticosteroids
i. Topical corticosteroids applied to the scalp or eyebrows within 1 week
prior to randomization
ii. Systemic corticosteroids or immunosuppressants within 8 weeks prior
to randomization
iii. Intralesional corticosteroid injections for treatment of AA within
8 weeks prior to randomization
iv. Have had an intraarticular corticosteroid injection within 8 weeks prior
to randomization
b. JAK inhibitors
i. Topical JAK inhibitor applied to the scalp (eg, tofacitinib, ruxolitinib)
within 4 weeks prior to randomization.
ii. Oral JAK inhibitor within 8 weeks prior to randomization.
iii. Previously treated with an oral JAK inhibitor (eg, tofacitinib, ruxolitinib) and
had an inadequate response (for example, absence of significant terminal hair
growth after at least 12 weeks of treatment).
c. Other topical therapies (eg, anthralin, diphenylcyclopropenone or other
topical immunotherapies) for the treatment of AA within 4 weeks prior to
randomization.
d. Monoclonal antibody (eg, ustekinumab, secukinumab, adalimumab,
dupilumab) less than 5 half-lives prior to randomization.
e. Probenecid at the time of the randomization (Visit 2) that cannot be
discontinued for the duration of the study (probenecid may increase
baricitinib exposures).
f. Platelet-rich plasma within 8 weeks prior to randomization.
g. Phototherapy (UV therapy and laser on scalp lesions) within 4 weeks prior
to randomization.
h. HMG CoA reductase inhibitors or “Statins” (eg, simvastatin, simvastatin +
ezetimibe) for treatment of AA within 4 weeks prior to randomization.
i. Cryotherapy for treatment of AA within 4 weeks prior to randomization
[10] Are largely or wholly incapacitated, permitting little or no self-care, such as
being bedridden.
[11] 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.
[12] 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 if participating in the trial.
[13] Are immunocompromised and in the opinion of the investigator, at an
unacceptable risk for participating in the study
[14] Have experienced any of the following within 12 weeks of screening:
myocardial infarction, unstable ischemic heart disease, stroke, or New York
Heart Association Stage III/IV heart failure.
[15] Have a history of VTE, or are considered at high risk for VTE, as deemed by
the investigator, or have 2 or more of the following risk factors for VTE:
a. Aged >65 years
b. BMI >35 kg/m2
c. Oral contraceptive use and current smoker status
[16] 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 IP or interfere
with the interpretation of data.
[17] 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 <5 years.
a. Patients with cervical carcinoma in situ that has been successfully treated
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 cell skin cancers that have been
successfully treated with no evidence of recurrence for at least 3 years may
participate in the study.
[18] Have a current or recent and/or serious viral, bacterial, fungal, or parasitic
infection, including but not limited to the following:
a. Symptomatic herpes zoster infection within 12 weeks prior to screening.
b. A history of disseminated/complicated herpes zoster (eg, multidermatomal
involvement, ophthalmic zoster, central nervous system 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 (IV) 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.
Note: A recent viral upper respiratory tract infection or uncomplicated urinary tract
infection should not be considered clinically serious.
[19] A history of eczema herpeticum within 12 months prior to screening.
[20] A history of 2 or more episodes of eczema herpeticum in the past.
[21] 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 (eg, atopic dermatitis, unstable chronic
asthma).
[22] 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 with the live herpes zoster vaccine can occur during the screening period
but must take place >4 weeks prior to randomization and start of IP. Vaccination
with the non-live herpes zoster vaccine requires at least 2 injections administered
8 weeks apart and, therefore, cannot be initiated after screening. Patients who have
initiated vaccination with non-live herpes zoster vaccine before the trial should have
received the second dose at least 4 weeks prior to randomization. Patients will be
excluded if they were exposed to herpes zoster vaccination within 4 weeks of planned
randomization.
[23] Have a history of chronic alcohol abuse, IV drug abuse, or other illicit drug
abuse within the 2 years prior to screening.
[24] 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 of 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 patient should be referred to a psychiatrist or appropriately trained
professional, as indicated.
[25] 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.
[26] 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.
[27] Have evidence of active TB or latent TB
a. Have evidence of active TB, defined in this study as the following:
i. Documented by a positive PPD test (≥5 mm of induration between
approximately 48 and 72 hours after application, regardless of
vaccination history), medical history, clinical features, and abnormal
chest x-ray at screening.
ii. The 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.