Active Non-segmental Vitiligo

Primary Objectives:  To evaluate the efficacy of PF-06651600 dose/dosing regimens at Week 24 in adult subjects with active non-segmental vitiligo.  To evaluate the safety and tolerability of PF-06651600 over time in adult subjects with active non-segmental vitiligo. Secondary Objectives:  To evaluate the efficacy of PF-06651600 compared to placebo as measured by other clinical assessments over time in adult subjects with active non-segmental vitiligo. Tertiary/Exploratory Objectives:  To evaluate the efficacy of PF-06651600 compared to placebo by other efficacy markers in adult subjects with active non-segmental vitiligo.  To assess PD and disease-related biomarkers over time in adult subjects with active non-segmental vitiligo.  To characterize PK of PF-06651600 over 24 weeks in adult subjects with active non-segmental vitiligo.  To collect banked biospecimens for exploratory research, unless prohibited by local regulations or ethics committee decision.  To evaluate the effect of PF-06651600 on psychological assessments over time in adult subjects with active non-segmental vitiligo.  To collect biopsy sub-studies samples in adult subjects with active non-segmental vitiligo.

PF-06651600 and PF-06700841

PF-06651600
PF-06700841

tablet
tablet

10 and 50
5 and 25

Primary Outcome Measures :
Percent change from baseline in central read facial- vitiligo area scoring index (facial-VASI) at Week 24 [ Time Frame: baseline, 24 weeks ]
central assessment of facial vitiligo lesion to measure efficacy of PF-06651600

Number of treatment emergent adverse events (TEAEs) [ Time Frame: baseline up to end of study (56 weeks) ]
Number of subjects with change from baseline in laboratory tests results [ Time Frame: baseline to end of study (56 weeks) ]
Number of subjects reporting TEAEs [ Time Frame: baseline up to end of study (56 weeks) ]
Number of specific clinical laboratory abnormalities [ Time Frame: baseline to end of study (56 weeks) ]
Number of treatment emergent serious adverse events (TESAEs) [ Time Frame: baseline to end of study (56 weeks) ]
number of subjects who experienced TESAEs [ Time Frame: baseline to end of study (56 weeks) ]

1. Evidence of a personally signed and dated informed consent document indicating that
the subject 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 between 18-65 years of age, inclusive, at time of informed consent.
4. Female subjects of childbearing potential and at risk for pregnancy must agree to use
one method of contraception (per Section 4.4.1) throughout the study and for at least
28 days after the last dose of assigned treatment.
Female subjects of non-childbearing potential must meet at least 1 of the following criteria:
a. Achieved postmenopausal status, defined as follows: cessation of regular menses
for at least 12 consecutive months with no alternative pathological or
physiological cause; status may be confirmed with a serum follicle-stimulating
hormone (FSH) level confirming the postmenopausal state;
b. Have undergone a documented hysterectomy and/or bilateral oophorectomy;
c. Have medically confirmed ovarian failure.
All other female subjects (including female subjects with tubal ligations) are considered to be of childbearing potential.
Note: For all subjects assigned to Group 1 in the Extension Period, please refer to Section 4.4.1.
5. Must meet the following active non-segmental vitiligo criteria at the Screening Visit and the Baseline Visit:
a. Have a clinical diagnosis of non-segmental vitiligo for at least 3 months; and
b. Body surface area (BSA) involvement 4% - 50% excluding involvements at
palms of the hands, dorsal aspect of fingers and thumbs including
metacarpophalangeal joints, soles of the feet, or dorsal aspect of the feet; and
c. BSA 0.25% involvement on the face excluding involvement at vermilion (confirmed by photographs); and
d. Subjects should have at least one active lesion defined as one of the following:
(i) New/extending lesion(s) in the past 3 months (confirmed by photographs or medical record);
(ii) Confetti-like lesion(s);
(iii) Trichrome lesion(s);
(iv) Koebner phenomenon/ phenomena [excluding Type 1 (history based isomorphic reaction)];
e. Coexistence of halo nevus/nevi (also known as Sutton nevus/ nevi) is permitted.
6. If receiving concomitant medications for any reason other than vitiligo, must 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 (Section 5.8.1).
7. Must agree to avoid prolonged exposure to the sun and not to use tanning booths, sun
lamps or other ultraviolet light sources other than provided/requested by the study
team during the study (Section 4.4 Lifestyle Requirements).

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. Other acute or chronic medical or laboratory abnormality that may increase the risk
associated with study participation or investigational product administration or may
interfere with the interpretation of study results and, in the judgment of the
investigator or sponsor, would make the subject inappropriate for entry into this study.
3. Any psychiatric condition including recent or active suicidal ideation or behavior that
meets any of the following criteria:
 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) (Section 7.5).
 Previous history of suicidal behaviors in the past 5 years: “Yes” answer (for events that occurred in the past 5 years) to any of the suicidal behavior items of the C-SSRS.
 Any lifetime history of serious or recurrent suicidal behavior.
 Clinically significant depression: patient health questionnaire – 8 items (PHQ-8) (Section 7.6.5) total score 15.
 The presence of any current major psychiatric disorder that is not explicitly permitted in the inclusion/exclusion criteria.
 In the opinion of the investigator or Pfizer Medical Monitor (or designee), exclusion is required.
4. Subjects considered in imminent need for surgery (for example in the next 6 months) or with elective surgery scheduled to occur during the study.
5. Subjects that have other types of vitiligo (including but not limited to segmental vitiligo). Note: Mixed vitiligo is permitted.
6. Currently have active forms of other hypopigmentation (including but not limited to Vogt-Koyanagi-Harada disease, malignancy-induced hypopigmentation [melanoma and mycosis fungoides], post-inflammatory hypopigmentation, pityriasis alba [minor manifestation of atopic dermatitis], senile leukoderma [age-related depigmentation],
chemical/ drug-induced leukoderma, ataxia telangiectasia, tuberous sclerosis, melasma, and congenital hypopigmentation disorders including piebaldism, Waardenburg syndrome, hypomelanosis of Ito, incontinentia pigmenti,
dyschromatosis symmetrica hereditaria, xeroderma pigmentosum, and nevus depigmentosus). Note: Coexistence of halo nevus/ nevi (also known as Sutton nevus/ nevi) is permitted.
7. Currently have active forms of inflammatory skin disease(s) or evidence of skin conditions (including but not limited to morphea, discoid lupus, leprosy, syphilis, psoriasis, seborrheic dermatitis) at the time of the Screening or Day 1 Visit that in the
opinion of the investigator would interfere with evaluation of vitiligo or response to treatment.
8. Have received any of the following treatment regiments specified in the timeframes outlined below:
At any time:
 Use of permanent depigmentation treatment for vitiligo and/or other types of pigmentation disorders (eg, monobenzone or phenol).
Within 6 months of Day 1:
 Any cell-depleting agents including but not limited to rituximab: within 6 months of Day 1, or 5 half-lives (if known), or until lymphocyte count returns to normal, whichever is longer.
Within 12 weeks of Day 1:
 Use of JAK inhibitors
 Other biologics: within 12 weeks of Day 1 or 5 half-lives (if known), whichever is longer.
Within 8 weeks of Day 1:
 Systemic treatments that could affect vitiligo within 8 weeks of Day 1 or within 5 half-lives (if known), whichever is longer.
 Use of oral immune suppressants (eg, cyclosporine A, azathioprine, methotrexate [MTX], sulfasalazine, systemic corticosteroids, mycophenolate-mofetil,) within 8 weeks of Day 1 or within 5 half-lives (if known), whichever is longer.
 Intralesional steroid injection within 8 weeks of Day 1 or within 5 half-lives (if known), whichever is longer.
 Participation in other studies involving investigational drug(s) within 8 weeks of Day 1 or within 5 half-lives (if known), whichever is longer and/or during study participation.
Note: Any investigational or experimental therapy taken or procedure performed for vitiligo and other diseases including but not limited to rheumatoid arthritis, psoriasis, alopecia areata, thyroid disease, allergic rhinitis, or atopic dermatitis
within the previous 1 year should be discussed with the Pfizer Medical Monitor (or designee). Subjects cannot participate in studies of other investigational or experimental therapies or procedures at any time during their participation in this study.
Within 6 weeks of Day 1:
 Live or attenuated live vaccine.
Within 4 weeks of Day 1:
 Ultra-Violet B (UVB) phototherapy, Psoralen Ultra-Violet A therapy, or other phototherapy.
Within 2 weeks of Day 1:
 Topical treatments that could affect vitiligo (eg, corticosteroids, vitamin D3, and calcineurin inhibitor).
Within 1 week of Day 1:
 Herbal medications with unknown properties or known beneficial effects for vitiligo.
9. Pregnant female subjects; breastfeeding female subjects; and female subjects of
childbearing potential who are unwilling or unable to use one method of
contraception as outlined in this protocol for the duration of the study and for at least
28 days after the last dose of investigational product.
10. Have 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, 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; history of severe allergic or anaphylactoid reaction to kinase inhibitors; 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 Section 6 Study Procedures
and Section 4.4 Lifestyle Requirements.
11. Have hearing loss with progression over the previous 5 years, 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 current, fluctuating or
progressive.
12. Have a 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. Have a history (single episode) of disseminated herpes zoster or disseminated herpes
simplex, or a recurrent (more than one episode of) localized, dermatomal herpes zoster.
14. Have a 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.
15. Have active acute or chronic skin infection requiring treatment with systemic
antibiotics, antivirals, antiparasitics, antiprotozoals, or antifungals within 4 weeks
prior to Day 1, or superficial skin infections within 2 weeks prior to Day 1.
NOTE: patients may be rescreened after the infection resolves.
16. Have a history of alcohol or substance abuse within 6 months prior to Day 1 that in
the opinion of the investigator or Pfizer (or designee) will preclude participation in
the study or protocol adherence in the study.
17. ANY of the following conditions at screening:
a. 12-lead electrocardiogram (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 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.
18. Have a known immunodeficiency disorder or a first-degree relative with a hereditary immunodeficiency.
19. Abnormal findings on the screening chest radiographs (eg, chest X-ray) including, but
not limited to, presence of TB, general infections, heart failure, or malignancy. Chest
radiographs examination may be performed up to 12 weeks prior to Day 1.
Documentation of the official reading must be available in the source documentation.
20. Have any malignancies or have a 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.
21. Have undergone significant trauma or major surgery within 1 month of the first dose of IP.
22. Require treatment with prohibited concomitant medication(s) (Section 5.8.3 and
Appendix 2) or have received a prohibited concomitant medication within 7 days or
5 half-lives (whichever is longer) prior to Day 1.
23. History of human immunodeficiency virus (HIV) or positive HIV serology at screening.
24. Infected with hepatitis B or hepatitis C viruses. For Hepatitis B, all subjects will
undergo testing for Hepatitis B Surface Antigen (HBsAg) and Hepatitis B Core
Antibody (HBcAb) during Screening. Subjects who are HBsAg positive are not
eligible for the study. Subjects who are HBsAg negative and HBcAb positive will be
reflex tested for Hepatitis B Surface Antibody (HBsAb) and if HBsAb is positive,
may be enrolled in the study; if HBsAb is negative, the subject is not eligible for the
study. For Hepatitis C, all subjects will undergo testing for Hepatitis C antibody
(HCVAb) during Screening. Subjects who are HCVAb positive are not eligible for
the study. Note: For Japan, Korea and Taiwan, please refer to Appendix 10.
25. Infected with Mycobacterium tuberculosis (TB) as defined by the following:
a. A positive Interferon Gamma Release Assay (IGRA) test or positive
Mantoux/Purified Protein Derivative (PPD) tuberculin skin test performed at or
within the 12 weeks prior to Day 1 is exclusionary; a negative test is required for
eligibility. It is strongly recommended that subjects with a history of Bacille
Calmette Guérin (BCG) vaccination be tested with the IGRA test since the
Mantoux/PPD tuberculin skin test may be positive due to vaccination. See
Section 7.3.5 for requirements for Mantoux/PPD tuberculin skin testing. The
following are acceptable IGRA assays: QuantiFERON
- TB Gold test (QFT-G), QuantiFERON
- TB Gold In-Tube test (QFT-GIT) and T-SPOT

 If the results of the IGRA are indeterminate, the test may be repeated, and if a negative result is obtained, enrollment may proceed. A positive test on repeat is exclusionary.
 Subjects with repeat indeterminate IGRA results may be enrolled after
consultation with pulmonary or infectious disease specialist who determines
that the risk of infection is low (ie, subject would be acceptable for
immunosuppressant treatment without additional action).
 Subjects who test positive for IGRA test (including borderline T-SPOT
result), but in the opinion of the principal investigator (PI) are at low risk of
TB infection may be referred to pulmonary or infectious disease specialist for
consultation and may have the IGRA test repeated once. Subjects will be
eligible if the repeat test is negative before the randomization.
b. Chest radiograph taken at screening (or performed and documented within
3 months prior to Day 1) with changes suggestive of active TB infection.
c. A subject who has been treated or is currently being treated for active or latent TB infection is to be excluded.
d. A history of either untreated or inadequately treated latent or active TB infection is to be excluded.
26. Donation of blood in excess of 500 mL within 8 weeks prior to Day 1.
27. 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:
 Absolute neutrophil count of <2.5 x 109 /L (<2500/mm3);
 Hemoglobin <10.0 g/dL or hematocrit <30%;
 Platelet count below the lower limit of normal (LLN) at Screening;
 Absolute lymphocyte count of <0.8 x 109 /L (<800/mm3);
 Serum creatinine > upper limit of normal (ULN) or eGFR <60 ml/min/1.73m2 based on the age appropriate calculation;
 Enzymes aspartate transaminase (AST) or alanine transaminase (ALT) values >2 times the ULN;
 Total bilirubin 1.5 times the ULN; subjects with a history of Gilbert's syndrome may have a direct bilirubin measured and would be eligible for this study provided the direct bilirubin is
 ULN;
 Creatine kinase (CK) >3 times the ULN and positive urine myoglobin;
 Glycosylated hemoglobin A1c (HbA1c) >10%;
 In the opinion of the investigator or Pfizer (or designee), have any uncontrolled
clinically significant laboratory abnormality that would affect interpretation of
study data or the subject’s participation in the study.