Ritlecitinib (PF-06651600) in Participants With Chronic Spontaneous Urticaria

INCLUSION CRITERIA:

Participants are eligible to be included in the study only if all the following criteria apply:

• Participant has been informed about study procedures and medications and hasprovided informed consent prior to initiation of any study-specificactivities/procedures

• Participant is able to communicate with the investigator, and understands andcomplies with the requirements of the study

• Age ≥ 18 to ≤ 65 years of age at screening

• Participant has a negative Tuberculin purified protein derivative (PPD) orQuantiFERON TBGold test (QFT) at screening or within the last 12 months.

• Chronic spontaneous urticaria diagnosis ≥ 3 months at the time of screening visit 1

• Diagnosis of CSU inadequately controlled by second-generation H1-antihistamines (sgAH) at enrollment, as defined by the following:

• The presence of itch and hives for ≥ 6 consecutive weeks at any time prior toscreening visit 2 despite current use of an approved dose of H1-antihistamine

• Urticaria Activity Score over 7 days (UAS7) (range 0-42) ≥ 16 and Hive SeverityScore over 7 days (HSS7) (range 0-21) ≥ 8 during the 7 days prior to enrollment

• Participant must have been on or failed a sgAH at approved or increased doses (up to 2 or 4x the approved dose) for treatment of CSU prior to the Baseline visit and musthave documented current use on the day of screening visit ○ If participants arecurrently on a sgAH, they must continue the same dose throughout the trial

EXCLUSION CRITERIA:

Disease Related

• Urticaria is solely due to inducible urticaria

• Active dermatologic diseases (or conditions) other than chronic urticaria, withurticaria wheals or angioedema symptoms such as urticarial vasculitis, erythemamultiforme, cutaneous mastocytosis (urticaria pigmentosa) and hereditary or acquiredangioedema (eg, due to C1 inhibitor deficiency)

• Any other active skin disease associated with chronic itching that might influence,in the investigator's opinion, the study evaluations and results (eg, atopicdermatitis, dermatitis herpetiformis, senile pruritus, etc.)

Other Medical Conditions

• History of, or a concurrent, clinically significant illness, medical condition orlaboratory abnormality that, in the investigator's opinion, could affect the conductof the study

• Active immunosuppression by previous (5 x half-lives or 12 weeks, whichever islonger) or current systemic cytotoxic therapies

• Uncontrolled current illness, including, but not limited to the following: Ongoingor active infections requiring intravenous antimicrobials; symptomatic congestiveheart failure defined as NYHA class III or IV; unstable angina pectoris within 6months of study enrollment; history of myocardial infarction, stroke or intracranialhemorrhage within 6 months prior to enrollment; moderate to severe hepaticimpairment (Child-Pugh class B or C); psychiatric illness or social situations thatwould limit compliance with study requirements

• Previous or current cancer, except curatively treated basal or squamous cellcarcinoma of the skin, and curatively treated malignant melanoma stage 0-1A with alow risk of recurrence/metastasis as per assessment of the investigator, cervicalcarcinoma in situ, treated basal cell carcinoma, superficial bladder tumors (Ta, Tisand T1)

• Known HIV infection

• Infected with Hepatitis B or Hepatitis C viruses

• Participants with history of either untreated or inadequately treated latent oractive TB infections/currently being treated for active TB

• Recent (within 21 days before visit 1) major surgery

• Participants who have history of a single episode of disseminated HZ or disseminatedHS or recurrent (> 1 episode of) localized dermatomal HZ should be excluded

• Any gastrointestinal or metabolic condition that could interfere with the absorptionof the oral medication

• History of thrombosis/thromboembolic event, known coagulopathy

• 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'sdisease, labyrinthitis, or other auditory condition that is considered current,fluctuating, or progressive.

• Abnormality in hematology, chemistry profiles, or ECG during screening:

• Platelet count: <100,000/ mm3

• Lymphocytes: <600/ mm3

• Absolute neutrophil count: <1200/ mm3

• Hemoglobin: <9.0 g/dL

• ALT or AST: >3.0xULN

• eGFR: <30 mL/min

• ECG that demonstrates clinically relevant abnormalities that may affectparticipant safety

Prior/Concomitant Therapy

• Less than 3 months have elapsed since last JAK inhibitors

• Glucocorticosteroids when used systematically within 1 month prior to visit 2

• Prior treatment with other concomitant investigational agents

• Hypersensitivity or allergic reaction to compounds related to JAK inhibitors

• Treatment with medication that might interfere with blood levels or have a majorimpact on the clinical readout of the study drug, as per discretion of the studyinvestigator

• Participants who have received prohibited drugs that are CYP3A inducers within a 28day or 5 half-lives (whichever is longer) period prior to the first dose of studyintervention

• Participants who have received prohibited drugs that are CYP3A4 or CYP1A2 substrateswith narrow therapeutic index where small concentration changes may lead to seriousadverse reactions within 1 week or 5 half-lives (whichever is longer) period priorto the first dose of study intervention

• Participant has received a live attenuated vaccine ≤ 30 days prior to studyscreening

• Treatment with any anti-IgE therapies (eg, omalizumab, ligelizumab) within 1 monthsprior to screening visit

Other Exclusions

• Pregnant or breast-feeding women

• Unwillingness or inability to use a contraception method during the time ofparticipation in the trial

• Active alcohol and/or drug abuse

• Participant is unable to complete a participant diary or complete questionnaires, ordoes not meet the required level of compliance (≥ 80%) with the diary