A Phase 2 Multicenter Study to Evaluate PF-06823859 in Adult Participants With Active CLE or SLE With Cutaneous Manifestations

Prior treatment

• Significant trauma or major surgery or blood transfusion within 5 weeks of screening, or scheduled to occur during the study, excluding diagnostic surgery.
• History of alcohol or drug abuse in investigator’s opinion unless in full remission for greater than 12 months prior to first dose of study intervention.
• Screening chest X-ray with changes suggestive of active infection, prior untreated TB, heart failure, suspected malignancy, or any other clinically significant disease in the chest.
• Additional immunomodulatory drug exclusions.
• Have received plasmapheresis within 12 weeks of screening or IVIg within 24 weeks of screening.
• Treatment with any investigational drug(s) within 12 weeks of Day 1 for investigational biologics or within one month or 5 half-lives for investigational small molecules whichever is longer, and/or during study participation.
• Has been exposed to a live vaccine within 8 weeks of Day 1 or are expected to need/receive a live vaccine during the course of the study. Participants should not have received a BCG vaccination within 52 weeks of randomization.
• Participation in other interventional studies within 12 weeks or 5 half-lives, if known, whichever is longer, prior to study entry and/or during study participation.
• Active, severe lupus nephritis that requires or may require treatment with cytotoxic agents or high-dose CS.

Other illness

• Have another skin disorder that would confound the results of the skin biopsy or clinical assessments in the study.
• Cancer or any history of cancer within 5 years of screening (except adequately resected skin basal cell carcinoma, squamous cell carcinoma, or carcinoma in situ of the uterine cervix without recurrence within the previous 5 years).
• History of a major organ transplant or hematopoietic stem cell/marrow transplant or total lymphoid irradiation.
• Have a history of: • A history of major cardiovascular or cerebrovascular event (stroke) or acute cardiac syndrome (MI, unstable angina pectoris, coronary stenting) within 24 months of screening. • known pulmonary arterial hypertension, • history of pulmonary embolism within 6 months of screening.
• Preexisting demyelinating disorder such as multiple sclerosis, or other severe neurological deficits.
• Have any autoimmune or inflammatory disease that would interfere with interpretation of test results or clinical assessments.
• History of any lymphoproliferative disorder such as EBV related lymphoproliferative disorder, history of lymphoma, leukemia, or signs and symptoms suggestive of lymphoproliferative disease, including lymphadenopathy or splenomegaly.
• Have required management of acute or chronic infections.
• Participants with a history of hypersensitivity reactions to active drug or any of the excipients in the rug product or placebo.
• Infected with Mycobacterium TB: active TB or latent TB.
• Known history of HIV based on documented history with positive test, or positive HIV test at screening.
• Have evidence of active or latent infection of hepatitis B or hepatitis C based on screening tests.
• Screening 12-lead ECG that demonstrates clinically significant abnormalities requiring treatment or that are indicative of serious underlying heart disease and other clinically relevant abnormalities which may affect participant safety or interpretation of study results.

Lab values

• Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation.
• Use of filgrastim, pegfilgrastim, erythropoietin or other bone marrow stimulants to improve cell counts within 12-week of screening.

Other

• History (single episode) of disseminated herpes zoster or disseminated herpes simplex, or recurrent (more than 1 episode within last 5 years) localized, dermatomal herpes zoster.
• Participants who are currently vaping or using e-cigarettes.
• Severe active CNS lupus requiring therapeutic intervention within 60 days of Day 1.
• Clinically significant lab abnormalities.
• Investigator or site staff directly involved in the conduct of the study and their family members.

• Male or female participants between the ages of 18 (or the minimum country specific age of consent if >18) and 75 years, inclusive, at the time of signing the ICD.
• Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.
• Participants must be willing to avoid application of topical medications to the index lesions (4 index lesions should be identified at screening and baseline) that are identified for potential biopsies in the study until after Week 32.
• Participants must have adequate IV access for administration of study intervention and on-study blood sampling.
• Have a diagnosis of histologically confirmed active CLE or SLE with cutaneous manifestations despite treatment with standard of care medications for at least 12 weeks defined as a score of ≥8 on the CLASI-A, an erythema score of ≥2 in the CLASI and historical biopsy (report to be available to disease activity adjudicators) within the past 10 years with either: a. Subacute cutaneous lupus erythematosus, or b. Discoid lupus erythematosus with at least one active discoid lesion (panniculitis, tumidus and chilblain lesions are excluded for the purposes of disease activity qualifying for eligibility and biopsy but are not exclusionary), or c. Both subacute and chronic cutaneous lupus erythematosus
• All participants may be currently receiving EITHER a stable dose of an immunosuppressant (MTX, AZA, 6-MP, leflunomide, mizoribine, MMF), or dapsone or colchicine with or without antimalarials and/or corticosteroids, OR anti-malarials (hydroxychloroquine, chloroquine or quinacrine) in combination with corticosteroids (dose of oral corticosteroids must be between 5 and 10 mg/day prednisone equivalent) or permitted topical agents.
• Participants weighing greater than 40 kg and less than 130 kg and with a BMI of <40 kg/m2.