Clinical presentation of scarring alopecia without active inflammation at screening.
Diagnosis consisting of frontal fibrosing alopecia (FFA) without active patches of classic LPP at screening
Clinical diagnosis, histology, or symptoms consistent with discoid lupus.
Hair transplant (e.g., follicular unit extraction, follicular unit transplantation) or facial reconstructive and/or aesthetic procedures involving the scalp and/or hair line (e.g., facial lifting procedures, facial tightening procedures, rhytidectomies, paramedian forehead flap reconstruction) within 1 year of baseline (Day 1/Visit 2).
Any surgical procedure on the scalp (except those described in Exclusion #4) within 6 months prior to baseline (Day 1/Visit 2).
Clinically significant manifestations of LP other than LPP (e.g., mucosal or cutaneous LP) at screening that, in the opinion of the investigator, would pose any additional safety risks or impact compliance with study procedures (e.g., discontinuation of LP-directed therapies).
Ongoing or planned treatment with any prohibited medications, including topical or systemic anti-inflammatory or immunomodulatory therapies for LPP.
Diagnosis of active inflammatory diseases of the scalp other than LPP that may interfere with the assessment of the study disease or require treatment with prohibited medications.
History of any lymphoproliferative disorder (such as Epstein-Barr virus [EBV]-related lymphoproliferative disorder, lymphoma, leukemia).
Cancer-associated condition, cancer, or history meeting any of the following conditions:
Active malignancy;
History of cancer within 5 years prior to randomization, with the exception of the following cancers with documentation of complete resection and no evidence of recurrence for ≥ 1 year:
Basal cell carcinoma, squamous cell carcinoma, ductal carcinoma in situ of the breast, carcinoma in situ of the uterine cervix, or thyroid carcinoma
Severe hepatic impairment, indicated by a Child-Pugh class C designation at screening.
History of any of the following:
Thrombosis or cerebrovascular ischemic event within the last 12 months prior to baseline (Day 1/Visit 2), or history of recurrent (≥ 2) venous thrombosis or arterial thromboembolism;
Known hypercoagulable state (for example, protein C deficiency, protein S deficiency, Factor V Leiden mutation, sickle cell disease, etc.), which in the opinion of the investigator, places the participant at high risk for thrombosis.
Any of the following cardiovascular risk factors:
A history of cardiac insufficiency defined as meeting either New York Heart Association (NYHA) Class III or Class IV criteria:
NYHA Class III: Marked limitation of physical activity; comfortable at rest; less than ordinary activity causes fatigue, palpitation, or dyspnea;
NYHA Class IV: Unable to carry on any physical activity without discomfort; symptoms of heart failure at rest; if any physical activity is undertaken, discomfort increases;
Current or not definitively managed clinically significant cardiac dysrhythmia;
Fridericia corrected QT interval (QTcF) > 450 msec for male participants or > 470 msec for female participants at screening, and confirmed by repeat ECG, if deemed necessary;
Unstable angina within 3 months prior to baseline (Day 1/Visit 2);
Myocardial infarction (MI) within 1 year prior to baseline (Day 1/Visit 2) (if ECG is indicative of current or prior coronary artery disease, and there is no known cardiac history, a cardiology consultation is required prior to entry);
Coronary artery bypass graft surgery within 1 year prior to baseline (Day 1/Visit 2).
Recipient of a solid organ or allogenic transplant who is currently receiving systemic immunosuppressive therapy.
Any condition possibly affecting oral drug absorption (e.g., gastrectomy, clinically significant diabetic gastroenteropathy, or certain types of bariatric surgery such as gastric bypass).
Any other acute or chronic medical condition, psychiatric condition, laboratory abnormality, or disease activity measures that, in the judgment of the investigator or sponsor, may increase the risk associated with study participation or investigational medicinal product (IMP) administration, or may interfere with the interpretation of study results, and would make the participant inappropriate for entry into this study.
Prior exposure to brepocitinib or participation in a brepocitinib clinical trial (randomized participants in Phase 2 of this protocol are not eligible for Phase 3); no therapeutic response, despite an adequate trial, of a marketed JAK inhibitor for prior treatment of lichen planus; or intolerance to a prior JAK or TYK2 inhibitor for any indication.
History of hypersensitivity to any constituents of the IMP formulation or other JAK inhibitors.
Has been exposed to a live vaccine within 6 weeks prior to baseline (Day 1/Visit 2) or is expected to need/receive a live vaccine during the course of the study. Participants must not have received a Bacillus Calmette-Guerin (BCG) vaccination within 52 weeks prior to baseline (Day 1/Visit 2).
Diagnosis of active infectious diseases of the scalp (e.g, bacterial, viral or fungal infections) that may interfere with the assessment of the study disease or require treatment with prohibited medications.
Active bacterial (with the exception of uncomplicated urinary tract infection), viral, fungal, mycobacterial, or other infections (including but not limited to tuberculosis and atypical mycobacterial disease, or allergic aspergillosis on chest x-ray), with the exception of infections that only require topical therapy, that would substantially increase the risk to the participant if they participate in the study.
History of recurrent bacterial (with the exception of uncomplicated urinary tract infection), viral, fungal (with the exception of infections that only required topical antifungal therapy), mycobacterial, or other infections (including but not limited to pyelonephritis, TB and atypical mycobacterial disease on chest x-ray) that would substantially increase the risk to the participant if they participate in the study.
Have required management of acute or chronic infections as follows:
Currently on suppressive therapy for any chronic infection (e.g., pneumocystis, cytomegalovirus [CMV], and atypical mycobacteria) that, in the opinion of the investigator and sponsor, would place the participant at risk for reactivation and/or infection
Hospitalization for infection within 60 days prior to baseline (Day 1/Visit 2).
Use of intravenous (IV) or intramuscular (IM) antibacterials, antivirals, antifungals, or anti-parasitic agents within 60 days prior to baseline (Day 1/Visit 2)
Use of oral antibiotics to treat an active infection within 14 days prior to baseline (Day 1/Visit 2).
History of disseminated herpes zoster, history of disseminated herpes simplex, or recurrent (≥ 2 episodes within last 5 years prior to baseline, Day 1/Visit 2) localized, single unilateral dermatomal herpes zoster.
Infection with Mycobacterium tuberculosis as defined by any of the following with a tuberculosis (TB) test performed at screening or within 12 weeks prior to screening:
A positive interferon gamma release assay (IGRA), noting the following:
If the results of the IGRA are indeterminate, the test may be repeated once, and if a negative result is obtained, enrollment may proceed. A positive test on repeat is exclusionary.
Participants with repeat indeterminate IGRA results should have a different IGRA performed (e.g., T spot) and may be enrolled after consultation with an infectious disease and/or pulmonary specialist and sponsor agreement.
Participants who have previously completed an adequate course of therapy (in the opinion of an infectious disease and/or pulmonary specialist provided within the 6 months prior to screening) for latent TB infection may be enrolled regardless of screening IGRA results provided that 1) there are no current signs or symptoms of active TB and 2) the treatment is well documented in the participant’s medical records.
Participants who are diagnosed with latent TB prior to or during screening and require current treatment should initiate the treatment before enrollment. Participants in this case will be eligible for the study only if the participant is seen by an infectious disease and/or pulmonary specialist and confirmed to have no findings of active TB and if the consultant agrees that the participant’s latent TB can be adequately treated with isoniazid (INH) plus vitamin B6. The participant must agree to complete the course of INH and vitamin B6 during the study. Additional management of latent TB should follow local guidelines or recommendations.
Note: A historical NEGATIVE IGRA result from a test that was performed within the 12 weeks prior to screening can be used to establish eligibility, and repeat testing is not required.
Chest x-ray taken at screening with changes suggestive of active TB infection. Note: A chest x-ray or computed tomography [CT] or positron emission tomography [PET]-CT scan previously performed and documented within 6 months prior to screening does not require repeat.
Confirmed positive screening result for hepatitis B (hepatitis B surface antigen [HBsAg] positive; HBsAg negative, hepatitis B core antibody [HBcAb] positive, and hepatitis B surface antibody [HBsAb] negative; or HBV deoxyribonucleic acid [DNA] positive on reflex testing), hepatitis C (hepatitis C virus antibody [HCVAb] positive and hepatitis C virus [HCV] RNA positive on reflex testing), or human immunodeficiency virus [HIV] infection.
Confirmed positive screening result for hepatitis B (hepatitis B surface antigen [HBsAg] positive; HBsAg negative, hepatitis B core antibody [HBcAb] positive, and hepatitis B surface antibody [HBsAb] negative; or HBV deoxyribonucleic acid [DNA] positive on reflex testing), hepatitis C (hepatitis C virus antibody [HCVAb] positive and hepatitis C virus [HCV] RNA positive on reflex testing), or human immunodeficiency virus [HIV] infection.
Any of the following abnormalities in clinical laboratory tests at screening and confirmed by repeat test, if deemed necessary:
Hemoglobin < 10 g/dL (100 g/L);
Platelet count < 100 × 109 /L (< 100,000/mm3 );
Absolute neutrophil count (ANC) < 1.5 × 109 /L (< 1500/mm3 );
Absolute lymphocyte count (ALC) < 0.80 × 109 /L (< 800/mm3 );
AST or ALT values > 3 × upper limit of normal (ULN);
Total bilirubin > 1.5 × ULN; participants 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;
CK > 3 × ULN. Participants with CK > 3 × ULN and ≤ 5 × ULN will be permitted with approval of the medical monitor if the CK elevation is considered physiologic or benign in nature.
Have had significant trauma, invasive surgery, or blood transfusion within 8 weeks prior to baseline (Day 1/Visit 2) or scheduled to occur during the study, unless approved by the medical monitor.
History of alcohol or drug abuse, in the investigator’s opinion, unless in full remission for greater than 12 months prior to baseline (Day 1/Visit 2).
Women who are breastfeeding, pregnant, or planning to become pregnant, or WOCBP who are unwilling to apply a highly effective birth control method for the time periods specified, and up to 28 days after the last dose of study drug.
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 Priovant Therapeutics, Inc. or affiliate employees, including their family members, directly involved in the conduct of the study