A 52-Week Study of Ritlecitinib Oral Capsules in Adults and Adolescents With Nonsegmental Vitiligo (Active and Stable) Tranquillo

Inclusion Criteria:

1. Participants ≥18 years of age at Screening. Adolescents (12 to <18 years of age) arealso eligible for this study, but only if approved by the local IRB/EC andregulatory health authority. Where these approvals have not been granted, onlyparticipants ≥18 years of age will be enrolled. Disease Characteristics:

2. Eligible participants must have at both Screening and Baseline:

• A clinical diagnosis of nonsegmental vitiligo for at least 3 months; and

• BSA involvement 4%-60% inclusive, excluding involvements at palms of the hands,soles of the feet, or dorsal aspect of the feet; and

• BSA ≥0.5% involvement on the face (face is defined as including the area on theforehead to the original hairline, on the cheek vertically to the jawline, andlaterally from the corner of the mouth to the tragus. The face will not includescalp, ears, neck, or surface area of the lips, but will include the nose andthe eyelids; and

• F-VASI ≥0.5 & T-VASI ≥3; and

• Either active or stable disease nonsegmental vitiligo at both Screening andBaseline visits. All participants who do not have the features of activevitiligo (defined below) are required to have stable disease. Active vitiligo is defined as:

• Participants will be classified as having active vitiligo based on the presenceof at least one active lesion at baseline defined as one of the following:

• New/extending lesion(s) in the 3 months prior to Screening visit (confirmed byphotographs or medical record):

• Confetti-like lesion(s); Confetti-like depigmentation is characterized by thepresence of numerous 1-mm to 5-mm depigmented macules in clusters;

• Trichrome lesion(s);Trichrome lesions have a hypopigmented zone of varyingwidth between normal and completely depigmented skin, resulting in 3 differenthues of skin;

• Koebner phenomenon/phenomena (excluding Type 1 [history based on isomorphicreaction]). The Koebner phenomenon manifests as depigmentation at sites oftrauma, usually in a linear arrangement. Stable vitiligo is defined as an absence of signs of active disease. Allparticipants who do not have the features of active vitiligo (defined above) arerequired to have stable disease. Eligibility is determined at Screening and Baseline based on the resulting scoresfrom the local in-person reads of F-VASI, T-VASI, and BSA. Other Inclusion Criteria:

3. If receiving concomitant medications for any reason other than vitiligo, participantmust be on a stable regimen, which is defined as not starting a new drug or changingdosage within 7 days or 5 half-lives (whichever is longer) prior to Day 1.Participant must be willing to stay on a stable regimen during the duration of thestudy.

4. Must agree to stop all other treatments for vitiligo from Screening through thefinal follow-up visit.

Exclusion Criteria:

1. Any psychiatric condition including recent or active suicidal ideation or behaviorthat meets any of the following criteria:

• Suicidal ideation associated with actual intent and a method or plan in thepast year: "Yes" answers on items 4 or 5 of the C-SSRS administered at thescreening visit.

• Previous history of suicidal behaviors in the past 5 years: "Yes" answer (forevents that occurred in the past 5 years) to any of the suicidal behavior itemsof the C-SSRS.

• For adults, any lifetime history of serious suicidal behavior or recurrentsuicidal behavior. For adolescents, any previous lifetime history of suicidalbehavior.

2. Medical conditions pertaining to vitiligo and other diseases/conditions affectingthe skin:

• Participants that have other types of vitiligo that do not meet criteria foractive or stable vitiligo as noted in inclusion criterion #2 (including, butnot limited to, segmental vitiligo and mixed vitiligo).

• Currently have active forms of other disorders of pigmentation (including butnot limited to Vogt-Koyanagi-Harada disease, malignancy-inducedhypopigmentation [melanoma and mycosis fungoides], post-inflammatoryhypopigmentation, pityriasis alba [minor manifestation of atopic dermatitis],senile leukoderma [age-related depigmentation], chemical/drug-inducedleukoderma, ataxia telangiectasia, tuberous sclerosis, melasma (all types,including mixed), and congenital hypopigmentation disorder includingpiebaldism, Waardenburg syndrome, hypomelanosis of Ito, incontinentia pigmenti,dyschromatosis symmetrica hereditarian, xeroderma pigmentosum, and nevusdepigmentosus). NOTE: Coexistence of halo nevus/nevi (also known as Suttonnevus/nevi) is permitted.

• Currently have active forms of inflammatory skin disease(s) or evidence of skinconditions (for example, morphea, discoid lupus, leprosy, syphilis, psoriasis,seborrheic dermatitis) at the time of the Screening or Baseline Visit that inthe opinion of the investigator would interfere with evaluation of vitiligo orresponse to treatment.

• Leukotrichia in more than 33% of the face surface area affected with vitiligolesions OR leukotrichia in more than 33% of the total body surface areaaffected with vitiligo lesions.

• Have a superficial skin infections within 2 weeks prior to first dose on Day 1.NOTE: participants may be rescreened after the infection resolves.

3. General Infection History:

• Having a history of systemic infection requiring hospitalization, parenteralantimicrobial, antiviral (including biologic treatment), antiparasitic,antiprotozoal, or antifungal therapy, or as otherwise judged clinicallysignificant by the investigator within 6 months prior to Day 1.

• Have active acute or chronic infection requiring treatment with oralantibiotics, antivirals, antiparasitics, antiprotozoals, or antifungals within 4 weeks prior to Day 1. NOTE: participants may be rescreened after theinfection resolves.

• Evidence or history of untreated, currently treated or inadequately treatedactive or latent infection with Mycobacterium TB

4. Specific Viral Infection History:

• History (single episode) of disseminated herpes zoster or disseminated herpessimplex, or a recurrent (more than one episode of) localized, dermatomal herpeszoster.

• Infected with hepatitis B or hepatitis C viruses: all participants will undergoscreening for hepatitis B and C for eligibility.

• Participants who are positive for HCVAb and HCV RNA will not be eligible forthis study.

• Have a known immunodeficiency disorder (including positive serology for HIV atscreening) or a first-degree relative with a hereditary immunodeficiency.

5. Medical Conditions, Other:

• Current or recent history of clinically significant severe, progressive, oruncontrolled renal (including but not limited to active renal disease or recentkidney stones), hepatic, hematological, gastrointestinal, metabolic, endocrine (eg, untreated hypovitaminosis D or hypothyroidism), pulmonary, cardiovascular,psychiatric, immunologic/rheumatologic or neurologic disease; or have any othersevere acute or chronic medical or psychiatric condition or laboratoryabnormality that may increase the risk associated with study participation orinvestigational product administration, or interfere with the interpretation ofstudy results; or in the opinion of the investigator or Pfizer (or designee),the participant is inappropriate for entry into this study, or unwilling/unableto comply with study procedures and lifestyle requirements.

• History of severe allergic or anaphylactoid reaction to any kinase inhibitor ora known allergy/hypersensitivity to any component (including excipients) of thestudy intervention.

• Have hearing loss with progression over the previous 5 years, sudden hearingloss, or middle or inner ear disease such as otitis media, cholesteatoma,Meniere's disease, labyrinthitis, or other auditory condition that isconsidered acute, fluctuating or progressive.

• Have a history of any lymphoproliferative disorder such as EBV-relatedlymphoproliferative disorder, history of lymphoma, history of leukemia, orsigns and symptoms suggestive of current lymphatic or lymphoid disease.

• Abnormal findings on the Screening chest imaging (eg, chest x-ray) that mayincrease the risk associated with study participation including, but notlimited to, presence of active TB, general infections, cardiomyopathy, ormalignancy. Chest imaging may be performed up to 12 weeks prior to screening.Documentation of the official reading must be located and available in thesource documentation.

• Long QT Syndrome, a family history of Long QT Syndrome, or a history of TdP.

• Have any malignancies or have a history of malignancies with the exception ofadequately treated or excised nonmetastatic basal cell or squamous cell cancerof the skin or cervical carcinoma in situ.

• Significant trauma or major surgery within 1 month of the first dose of studydrug or considered in imminent need for surgery or with elective surgeryscheduled to occur during the study. Prior/Concomitant Therapy:

6. Have received any of the prohibited treatment regimens specified. Prior/Concurrent Clinical Study Experience:

7. Previous administration with an investigational drug or vaccine that do not affectvitiligo within 4 weeks of Day 1 [Baseline] or within 5 half-lives, whichever islonger. Diagnostic Assessments:

8. Any of the following abnormalities in laboratory values at Screening, as assessed bythe study-specific laboratory and, if deemed necessary, confirmed by a singlerepeat:

• Renal impairment

• Hepatic dysfunction

9. Screening standard 12-lead ECG that demonstrates clinically relevant abnormalities Other Exclusion Criteria:

10. Investigator site staff directly involved in the conduct of the study and theirfamily members, site staff otherwise supervised by the investigator, and sponsor andsponsor delegate employees directly involved in the conduct of the study and theirfamily members.

11. Adolescent participants 12 to <18 years of age without one of the following:

• Documented evidence from a health professional of having received varicellavaccination (2 doses); or

• Evidence of prior exposure to VZV based on serological testing (ie, a positiveVZV IgG Ab result) at Screening.