Ritlecitinib in Patients With Keloids or Those Undergoing Keloidectomy

Inclusion Criteria:

• Male or female patients ≥ 18 years of age at the time of signing the informedconsent document (not more than 10% of the patients can be > 50 years of age).

• Patient is able to understand and voluntarily sign an informed consent documentprior to participation in any study assessments or procedures.

• Patient is able to adhere to the study visit schedule and other protocolrequirements.

• Patients who receive keloidectomy at Day 1/ Baseline only (Group 1): Patient hasminimum of one keloid measuring ≥2 cm in length on earlobe or ≥3.0 cm in length onareas) other than earlobe, which has failed prior minimally invasive treatments forkeloids including topicals and intralesional corticosteroid injections and that canbe surgically resected at Day 1/ Baseline.

• Patients who do not receive keloidectomy at Day 1/ Baseline only (Group 2):

• Patient has a minimum of either one keloid measuring ≥3 cm in length, ormultiple keloids, each measuring ≥1 cm in length , which failed prior minimallyinvasive treatments for keloids including topicals and intralesionalcorticosteroid injections. However, at least one keloid should not have beentreated with surgery, cryotherapy, radiation, or any other procedure that leadsto a deformity that interferes with proper clinical assessments.

• Patient reports either Pain-NRS ≥4 , Itch-NRS ≥4, or DLQI ≥8both at Visit 1 (Screening) and Visit 2 (Baseline)

• Patient is judged to be in otherwise good overall health as judged by theinvestigator, based on medical history, physical examination, and laboratorytesting. (NOTE: The definition of good health means a patient does not haveuncontrolled significant co-morbid conditions).

• Ability to take oral medication without crushing, dissolving or chewing tablets.

• Females of childbearing potential (FOCBP) must have a negative pregnancy test atScreening and Day 1/ Baseline. While on ritlecitinib and for at least 28 days aftertaking the last dose of ritlecitinib, FOCBP who engage in activity in whichconception is possible must use the approved contraceptive methods.

Exclusion Criteria:

• Patient has a persistent or recurring bacterial infection requiring systemicantibiotics, or clinically significant viral or fungal or helminth parasiticinfections, within 2 weeks of the Screening Visit. Any treatment of such infectionsmust have been completed at least 2 weeks prior to the Screening Visit and nonew/recurrent infections should have occurred prior to the Baseline Visit.

• Patient with current or history of positive human immunodeficiency virus (HIV), orcongenital or acquired immunodeficiency (i.e., Common Variable Immunodeficiency [CVID]), or active or untreated latent tuberculosis.

• Infected with hepatitis B or C virus.

• Patients who have history of single episode of disseminated herpes zoster (HZ) ordisseminated herpes simplex or recurrent (> 1 episode of) localized dermatomal HZ

• Patient has clinically significant (as determined by the investigator) renal,hepatic, hematologic, intestinal, endocrine, pulmonary, cardiovascular,neurological, psychiatric, immunologic, or other major uncontrolled diseases thatwill affect the health of the patient during the study or interfere with theinterpretation of study results.

• Patient has a suspected or active lymphoproliferative disorder or malignancy; OR ahistory of malignancy within 5 years before the Baseline assessment, except forcompletely treated in situ non-melanoma skin and cervical cancers without evidenceof metastasis.

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

• Active alcohol and/or drug abuse.

• History of thrombosis/ thromboembolic event, known coagulopathy.

• Additional skin disease that might interfere with keloid clinical assessments.

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

• Patient has received a live attenuated vaccine ≤ 30 days prior to study initiation.

• History of adverse systemic or allergic reactions to any component of the studydrug.

• Recent surgery excluding keloidectomy within 4 weeks and keloidectomy within 6months prior to trial initiation.

• Recent cryotherapy within 3 months, laser therapy within 3 months, or radiation orany other procedure within 6 months.

• Use of systemic immunosuppressive medications, including, but not limited to,cyclosporine, systemic or intralesional corticosteroids, mycophenolate mofetil,azathioprine, methotrexate, tacrolimus, or ultraviolet (UV) phototherapy with orwithout Psoralen Ultraviolet A (PUVA) therapy within 4 weeks prior to trialinitiation. Compression garments and silicone sheets may be allowed.

• Treatment with medication that might interfere with blood levels or have a majorimpact on the clinical readout of the study drug. This includes the following:

• Patient on concomitant medications that are substrates of CYP3A4 or CYP1A2 withnarrow therapeutic index where small concentration changes may lead to seriousadverse reactions

• Patient on concomitant medications that are strong inducers of CYP3A4 as thismight cause loss of efficacy of ritlecitinib

• Use of an oral JAK inhibitor (tofacitinib, ruxolitinib, ritlecitinib) within 3months prior to the Baseline visit.

• Patient has used topical corticosteroids, and/or tacrolimus, and/or pimecrolimus,and/or topical chemotherapy on any keloid lesions within 2 weeks prior to theBaseline visit. These will be allowed during the study on areas other than keloidlesions (if applicable) but not on any keloid lesions.

• Female patient who is pregnant or breast feeding

• FOCBP with unwillingness or inability to use a contraception method during the timeof participation in the trial (Appendix 1)

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

• Platelet count: <75000/ 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 affect patientsafety