A 104-Week Study of Ritlecitinib Oral Capsules in Adults With Nonsegmental Vitiligo (Active and Stable) Tranquillo 2

Inclusion Criteria:

1. Participants aged 18 years (or the minimum age of consent in accordance with localregulations) or older (no upper age limit) at Screening.

• Meeting reproductive criteria for female participants. Disease Characteristics:

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

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

• BSA involvement 4% to 60% inclusive, excluding involvements at palms of thehands, 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 to the jawline vertically tothe jawline and laterally from the corner of the mouth to the tragus. Face willnot include scalp, ears, neck, or surface area of the lips, but will includethe nose and the eyelids; and

• F-VASI ≥0.5 and T-VASI ≥3; and

• Either active or stable nonsegmental vitiligo at Screening and BL visits. Allparticipants who do not have the features of active vitiligo (defined below)will be classified as having stable disease. Active vitiligo is defined as: Participants will be classified as having active vitiligo based on the presence ofat least one active lesion at BL defined as one of the following:

• New/extending lesions(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:

• Participants will be classified as having stable vitiligo based on an absence ofsigns of active disease. All participants who do not have the features of activevitiligo (defined above) will be classified as having 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.

3. Additional inclusion criteria are:

• If receiving concomitant medications for any reason other than vitiligo,participant must be on a stable regimen, which is defined as not starting a newdrug or changing dosage within 7 days or 5 half-lives (whichever is longer)prior to Day 1. Participant must be willing to stay on a stable regimen duringthe duration of the study.

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

Exclusion Criteria:

Medical Conditions:

1. Any medical or psychiatric condition including recent (within the past year) oractive suicidal ideation/behavior or laboratory abnormality that may increase therisk of study participation or, in the investigator's judgment, make the participantinappropriate for the study.

• Any psychiatric condition including recent or active suicidal ideation or behaviorthat meets defined criteria.

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 criteria (including but notlimited to segmental vitiligo and mixed vitiligo).

• Currently have active forms of other hypopigmentation (including but notlimited 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, ataxiatelangiectasia, tuberous sclerosis, melasma, and congenital hypopigmentationdisorder including piebaldism, Waardenburg syndrome, hypomelanosis of Ito,incontinentia pigmenti, dyschromatosis symmetrica hereditarian, xerodermapigmentosum, and nevus depigmentosus). NOTE: Coexistence of halo nevus/nevi (also known as Sutton nevus/nevi) is permitted.

• Currently have active forms of inflammatory skin disease(s) or evidence of skinconditions (for example, but not limited to morphea, discoid lupus, leprosy,syphilis, psoriasis, seborrheic dermatitis) at the time of the Screening or BLVisit that in the opinion of the investigator would interfere with evaluationof vitiligo or response 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 infection within 2 weeks prior to first dose on Day 1.NOTE: participants may be rescreened after the infection resolves.

3. General Infection History:

• Have 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 tuberculosis.

4. Specific Viral Infection History:

• History (single episode) of disseminated HZ or disseminated herpes simplex orrecurrent (more than one episode of) localized, dermatomal HZ.

• Infected with HBV or HCV: all participants will undergo screening for HBV andHBC 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. Other Medical Conditions:

• 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 current, 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). Chestimaging may be performed up to 12 weeks prior to screening. Documentation ofthe official reading must be located and available in the source 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: Any of the following abnormalities in clinical laboratory tests at Screening, asassessed by the study-specific laboratory and, if deemed necessary, confirmed by asingle repeat:

8. Renal impairment

9. Hepatic dysfunction

10. Other laboratory abnormalities

11. Standard 12-lead ECG that demonstrates clinically relevant abnormalities Other Exclusion Criteria:

12. 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.

13. In South Africa only participants are excluded without one of the following:

• Document evidence form a health professional of having received varicellavaccination (two doses); or

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