Alopecia Areata (AA)

Primary Objective(s):  To evaluate the efficacy of PF-06651600 compared to placebo in adult and adolescent alopecia areata (AA) subjects with 50% or greater scalp hair loss on regrowth of lost hair (measured by an absolute Severity of Alopecia Tool (SALT) Score =<10).

PF-06651600

PF-06651600

tablet

10, 50

Response based on an absolute Severity of Alopecia Tool (SALT) Score ≦ 10 at Week 24.

1. Evidence of a personally signed and dated informed consent document indicating that
the subject or a legally acceptable representative/parent(s)/legal guardian has been
informed of all pertinent aspects of the study.
2. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
3. Male or female subjects age 12 years and older, inclusive, at time of informed
consent/assent. Adolescent subjects below the age of 18 years will only be enrolled
into this study if permitted by the sponsor, local competent authority, and institutional
review board (IRB)/ethics committee (EC). Otherwise, only subjects 18 years or
older (or age specified by applicable reviewer) will be enrolled in those countries,
regions, or sites.
4. Female participants are eligible to participate if they are not pregnant or
breastfeeding, and at least 1 of the following conditions applies:
a. Is a woman of childbearing potential (WOCBP) and using a contraceptive method
that is highly effective (with a failure rate of <1% per year), as described in
Section 4.3, during the intervention period and for at least 28 days after the last
dose of study intervention. The investigator should evaluate the effectiveness of
the contraceptive method in relationship to the first dose of study intervention.
OR
b. Is not a WOCBP (see definitions below):
Women in the following categories are not considered WOCBP:
 Premenarchal.
 Premenopausal female with 1 of the following:
 Documented hysterectomy;
 Documented bilateral salpingectomy;
 Documented bilateral oophorectomy.
For individuals with permanent infertility due to an alternate medical
cause other than the above, (eg, Müllerian agenesis, androgen
insensitivity), investigator discretion should be applied to determining
study entry.
Note: Documentation for any of the above categories can come from the
site personnel’s review of the participant’s medical records, medical
examination, or medical history interview. The method of documentation
should be recorded in the participant’s medical record for the study.
 Postmenopausal female:
A postmenopausal state is defined as age 60 years or older or no menses for
12 months without an alternative medical cause.
 A high follicle stimulating hormone (FSH) level in the postmenopausal
range must be used to confirm a postmenopausal state in women under
60 years old and not using hormonal contraception or hormone
replacement therapy (HRT).
 Females on HRT and whose menopausal status is in doubt will be required
to use one of the nonestrogen hormonal highly effective contraception
methods if they wish to continue their HRT during the study. Otherwise,
they must discontinue HRT to allow confirmation of postmenopausal
status before study enrollment.
The investigator is responsible for review of medical history, menstrual
history, and recent sexual activity to decrease the risk for inclusion of a
woman with an early undetected pregnancy. Documentation of this review
should be included in the participant’s medical record for the study.
5. Must meet the following AA criteria:
a. Have a clinical diagnosis of AA with no other etiology of hair loss (eg, telogen
effluvium, androgenetic alopecia, etc.).
b. 50% hair loss of the scalp, including alopecia totalis (AT) and alopecia
universalis (AU), without evidence of terminal hair regrowth within 6 months at
both the screening and baseline visits.
 AT is defined as complete (100%) scalp hair loss.
 AU is defined as complete (100%) scalp, facial, and body hair loss.
 Percentage of hair loss on the scalp will be measured by SALT (Appendix 5).
 Photographs taken at Screening must be submitted to the Sponsor or designee
for verification of SALT score 50 and hair loss due to AA. Subjects must
not be randomized until verification has been confirmed.
c. Current episode of hair loss ≤10 years.
6. If receiving permitted concomitant medications for any reason other than AA,
subjects should be on a stable regimen, which is defined as not starting a new drug or
changing dosage within 7 days or 5 half-lives (whichever is longer) prior to Day 1.
Subject must be willing to stay on a stable regimen during the duration of the study (see Section 5.8).
7. Must agree to avoid prolonged exposure to the sun and not to use tanning booths, sun
lamps or other ultraviolet light sources during the study.

1. Investigator site staff members directly involved in the conduct of the study and their
family members, site staff members otherwise supervised by the investigator, or
subjects who are Pfizer employees, including their family members, directly involved
in the conduct of the study.
2. Participation in other studies involving investigational drug(s) within 8 weeks or
within 5 half-lives (if known), whichever is longer, prior to study entry and/or during
study participation.
3. Other types of alopecia (including, but not limited to traction and scarring alopecia,
telogen effluvium). Subjects with known androgenetic alopecia will be excluded.
4. Other scalp disease that may impact AA assessment (eg, scalp psoriasis, dermatitis, etc).
5. Active systemic diseases that may cause hair loss (eg, lupus erythematosus,
thyroiditis, systemic sclerosis, lichen planus, etc).
6. Any psychiatric condition including recent or active suicidal ideation or behavior that
meets any of the following criteria:
a. Suicidal ideation associated with actual intent and a method or plan in the past
year: “Yes” answers on items 4 or 5 of the Columbia Suicide Severity Rating Scale (C-SSRS) (Appendix 6).
b. For subjects who had previous history of suicidal behaviors in the past >1 year to
<5 years: “Yes” answer (for events that occurred in the past 5 years) to any of the
suicidal behavior items of the C-SSRS or any lifetime history of serious or
recurrent suicidal behavior, a risk assessment must be performed, and
documented, by a qualified mental health professional to assess whether it is safe
for the subject to participate in the trial.
c. Clinically significant depression as indicated by a Patient Health Questionnaire -
8 Items (PHQ-8) (Appendix 13) total score ≥15.
d. The presence of any current major psychiatric disorder that is not explicitly
permitted in the inclusion/exclusion criteria.
7. Have hearing loss with progression over the previous 5 years, or sudden hearing loss,
or middle or inner ear disease such as otitis media, cholesteatoma, Meniere’s disease,
labyrinthitis, or other auditory condition that is considered acute, fluctuating or
progressive.
8. Received any of the following treatment regimens specified in the timeframes
outlined below:
a. At any time: previous use of any JAK inhibitor for use in any disease indication
or any non-B-cell selective lymphocyte-depleting agent (eg, alefacept,
alemtuzumab).
b. Within 6 months of first dose of study drug or 5 half-lives (if known), or until
lymphocyte count returns to normal, whichever is longer: any B-cell-depleting
agents including but not limited to rituximab.
c. Within 12 weeks of first dose of study drug or 5 half-lives (if known), whichever
is longer: other immunomodulatory biologic agents.
d. Within 8 weeks of first dose of study drug or within 5 half-lives (if known),
whichever is longer:
 Other systemic treatments that could affect AA including:
 Immune suppressants (eg, cyclosporine A, azathioprine, methotrexate
[MTX], sulfasalazine, mycophenolate mofetil [MMF]).
 Intralesional, oral, or injectable steroids.
 5α-Reductase inhibitors (5-ARIs) (eg, finasteride, dutasteride).
 Oral minoxidil.
 Spironolactone if used specifically for AA.
e. Within 6 weeks of first dose of study drug: vaccination with live or attenuated
live vaccine.
f. Within 4 weeks of first dose of study drug: Ultraviolet B (UVB) phototherapy,
Psoralen Ultraviolet A (PUVA) therapy, other phototherapy, contact
immunotherapy (eg, diphenylcyclopropenone [DPCP], squaric acid dibutylester
[SADBE], and 1-chloro-2,4-dinitrobenzene [DNCB]), topical irritants (eg,
anthralin), and liquid nitrogen cryotherapy.
g. Within 4 weeks of first dose of study drug or 5 half-lives (whichever is longer):
prohibited CYP3A inducers as described in Appendix 4
h. Within 2 weeks of first dose of study drug: topical treatments on areas under
assessment (ie, scalp, eyebrows, eyelashes, and fingernails) that could affect AA
(eg, steroid cream, medicated shampoo, minoxidil).
i. Within 10 days of first dose of study drug or 5 half-lives (if known), whichever is
longer: medications that prolong the time from the beginning of the QRS complex
to the end of the T wave (QT interval) (eg, azithromycin, citalopram, haloperidol).
A list of these medications can be found at
http://www.crediblemeds.org/index.php/login/dlcheck.
j. Within 1 week of first dose of study drug:
 Herbal medications with unknown properties or known effects for AA.
 Prohibited CYP3A inhibitors as described in Appendix 4 (within 7 days or
5 half-lives, whichever is longer).
 Prohibited CYP3A substrates as described in Appendix 4 (within 7 days or
5 half-lives, whichever is longer).
k. Subjects with shaved heads must not enter the study until hair has grown back and
is considered stable by the investigator.
9. Treatment anticipated with prohibited concomitant medication(s) (see Section 5.8.2
and Appendix 4) during the course of the study.
10. Current or recent history of clinically significant severe, progressive, or uncontrolled
renal (including but not limited to active renal disease or recent kidney stones),
hepatic, hematological, gastrointestinal, metabolic, endocrine (particularly thyroid
disease which can be associated with hair loss), pulmonary, cardiovascular,
psychiatric, immunologic/rheumatologic or neurologic disease; or have any other
severe acute or chronic medical or psychiatric condition or laboratory abnormality
that may increase the risk associated with study participation or investigational
product administration, or interfere with the interpretation of study results; or in the
opinion of the investigator or Pfizer (or designee), the subject is inappropriate for
entry into this study, or unwilling/unable to comply with STUDY PROCEDURES
and Lifestyle Requirements.
11. Any present malignancies or history of malignancies with the exception of adequately
treated or excised non-metastatic basal cell or squamous cell cancer of the skin or
cervical carcinoma in situ.
12. History of any lymphoproliferative disorder such as Epstein Barr Virus (EBV) related
lymphoproliferative disorder, history of lymphoma, history of leukemia, or signs and
symptoms suggestive of current lymphatic or lymphoid disease.
13. History (single episode) of disseminated herpes zoster or disseminated herpes
simplex, or a recurrent (more than one episode of) localized, dermatomal herpes
zoster.
14. Adolescent subjects 12 to <18 years-old without one of the following:
 Documented evidence of having received varicella vaccination (2 doses); or
 Evidence of prior exposure to varicella-zoster virus (VZV) based on serological
testing (ie, a positive VZV immunoglobulin G antibody [VZV IgG Ab] result) at
screening.
NOTE: Serological testing must be performed for VZV IgG Ab only in the
absence of documented evidence of having received varicella vaccination
(2 doses). If serological testing is performed, participants with a negative VZV
IgG Ab result are not eligible to enter the study, regardless of vaccination
history.
15. History of systemic infection requiring hospitalization, parenteral antimicrobial
therapy, or as otherwise judged clinically significant by the investigator within
6 months prior to Day 1 (for criteria regarding Tuberculosis [TB] infection, see
Exclusion Criterion 21).
16. Active acute or chronic infection requiring treatment with oral antibiotics, antivirals,
antiparasitics, antiprotozoals, or antifungals within 4 weeks prior to Day 1 or
superficial skin infection within 1 week prior to Day 1. NOTE: subjects may be
rescreened after the infection resolves.
17. Significant trauma or major surgery within 1 month of the first dose of study drug.
18. Considered in imminent need for surgery or with elective surgery scheduled to occur
during the study.
19. Known immunodeficiency disorder, including positive serology for human
immunodeficiency virus (HIV) at screening, or a first-degree relative with a
hereditary immunodeficiency.
20. Infection with hepatitis B or hepatitis C viruses according to protocol-specific testing
algorithm.
a. For hepatitis B, all subjects will undergo testing for hepatitis B surface antigen
(HBsAg) and hepatitis B core antibody (HBcAb). Subjects who are HBsAg
positive will not be eligible for this study. Subjects who are HBsAg negative but
HBcAb positive will be reflex tested for hepatitis B surface antibody (HBsAb).
Additional reflex testing for hepatitis B virus DNA testing (HBVDNA) is also
required for HBcAb positive subjects in countries in which Hep B prevalence has
been reported at a rate of >5.0% or if required by local standard of care. Please
refer to Appendix 2 for testing algorithm, reflex testing, and full eligibility
criteria. For Japan-specific requirements, see Appendix 18.1.
b. For hepatitis C, all subjects will undergo testing for hepatitis C antibody
(HCVAb) during Screening.
 Subjects who are HCVAb positive will be reflex-tested for hepatitis C RNA
(HCV RNA). Subjects who are HCVAb and HCV RNA positive are not
eligible for the study.
21. Have evidence of untreated or inadequately treated active or latent Mycobacterium
tuberculosis (TB) infection as evidenced by the following:
a. A positive QuantiFERON
-TB Gold In-Tube (QFT-G) test or positive or
borderline T-SPOT
.TB (T-Spot) test performed within the 3 months prior to
Baseline (Visit 2). If the laboratory reports the test as indeterminate, the test
should be repeated. If the result of the repeat test is indeterminate, a purified
protein derivative (PPD) test may be substituted for the QFT-G test or T-Spot test
only with approval from the Pfizer Medical Monitor on a case-by-case basis.
b. Chest radiograph with changes suggestive of active TB infection within 3 months
prior to Screening. Chest radiograph should be performed according to local
standards of care or country-specific guidelines.
c. History of either untreated or inadequately treated latent or active TB infection.
If a subject has previously received an adequate course of therapy for either latent
(9 months of isoniazid in a locale where rates of primary multi-drug resistant TB
infection are <5% or an acceptable alternative regimen) or active (acceptable
multi-drug regimen) TB infection, neither a QFT-G test, a T-Spot test, nor a PPD
test need be obtained. Details of the previous course of therapy (eg, medication(s)
used, dose, duration of therapy) should be documented in the source
documentation.
A chest radiograph should be obtained if not done within the 3 months prior to
Screening. To be considered eligible for the study, the chest radiograph must be
negative for active TB infection.
A subject who is currently being treated for active TB infection must be excluded
from the study.
A subject who is being treated for latent TB infection can only be enrolled with
confirmation of current incidence rates of multi-drug resistant TB infection,
documentation of an adequate treatment regimen, and prior approval of the
Sponsor.
22. Abnormal findings on the Screening chest radiographs (eg, chest x-ray) including, but
not limited to, presence of active TB, general infections, cardiomyopathy, or
malignancy. NOTE: Chest radiograph examination may be performed up to 3 months
prior to Screening visit. Documentation of the reading by a qualified radiologist or
pulmonologist must be available in the source documentation.
23. ANY of the following conditions at screening:
a. Screening 12-lead ECG that demonstrates:
 Clinically significant abnormalities requiring treatment (eg, acute myocardial
infarction, serious tachy- or brady-arrhythmias) or indicating serious
underlying heart disease (eg, cardiomyopathy, Wolff-Parkinson–White
syndrome);
 Confirmed QT interval corrected using Fridericia’s correction factor QTcF
(QTcF) prolongation (>450 milliseconds).
b. Long QT Syndrome, a family history of Long QT Syndrome, or a history of
Torsades de Pointes;
c. Use of concomitant medications that prolong the QT interval (as noted in
Exclusion Criterion 8i).
24. ANY of the following abnormalities in clinical laboratory tests at screening, as
assessed by the study-specific laboratory and confirmed by a single repeat, if deemed
necessary:
a. Absolute neutrophil count <1.2 x 109
/L (<1200/mm3
);
b. Hemoglobin <11.0 g/dL or hematocrit <33%;
c. Platelet count <150 × 109
/L or <150,000/mm3
;
d. Absolute lymphocyte count of <0.8 x 109
/L (<800/mm3
);
e. Estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m
2
based on the age
appropriate calculation;
f. Enzymes aspartate transaminase (AST) or alanine transaminase (ALT) values
>2 × upper limit of normal (ULN);
g. Total bilirubin >1.5 × ULN; subjects with Gilbert's syndrome would be eligible
for this study provided the direct bilirubin is ≤ULN;
h. In the opinion of the investigator or Pfizer (or designee), have any clinically
significant laboratory abnormality that that could affect interpretation of study
data or the subject’s participation in the study.
25. Have an active history of alcohol or substance abuse within 1 year prior to Day 1.
26. Donation of blood in excess of 500 mL within 8 weeks prior to Day 1.