A Phase 2 Study of Obexelimab in Patients with Systemic Lupus Erythematosus

Prior treatment

• Patients are excluded from the study if any of the following criteria apply: 1. Active lupus nephritis for which, in the opinion of the investigator or the central adjudicator, current medications are insufficient for patient’s safety or additional therapy that is not permitted in the protocol is needed.
• History of drug or alcohol abuse in the previous 12 months before screening in the opinion of the investigator.
• Use after the Screening visit of medical treatment (including prescription drugs, non-prescription drugs, biological products, Chinese or herbal medicines, diet supplements, etc.) or health care products considered by the investigator or central adjudicator to potentially impact the interpretation of study results.
• A history of thrombosis or embolism in the previous 6 months before the Screening visit, or thrombotic history in the previous 12 months associated with antiphospholipid syndrome (APS) or another relevant hypercoagulable state. A thrombotic history associated with APS or another relevant hypercoagulable state more than 12 months prior to Screening visit is excluded if it is not treated per local standards with prophylactic anticoagulation.
• Surgery (not considered minor by the investigator or the central adjudicator) within 4 weeks before Screening, or planned surgery during the study.

Other illness

• Malignancy within 5 years except successfully treated in situ cervical cancer, resected squamous cell or basal cell carcinoma of the skin.
• Any active skin conditions other than cutaneous lupus erythematosus (CLE) that may interfere with the study assessment of CLE, such as, but not limited to, psoriasis, dermatomyositis, and systemic sclerosis.
• Current inflammatory disease other than SLE (including, but not limited to, rheumatoid arthritis, psoriatic arthritis, spondyloarthropathy, reactive arthritis, scleroderma, dermatomyositis) that may interfere with the assessment of lupus signs and symptoms in the opinion of the investigator or central adjudicator. Current diagnosis of thyroiditis or secondary Sjogren's Syndrome is permitted.
• Presence of uncontrolled or New York Heart Association Class III or IV congestive heart failure.
• History of relevant allergies, including allergy to study drug or any murine or human-derived protein or immunoglobulin products that, in the opinion of the investigator or central adjudicator, make inclusion in the study inappropriate.

Lab values

• Use prior to screening of one or more of the following: a) Within 6 months: rituximab or similar major B cell-depleting biologic therapy, or T cell-depleting agent such as Campath (alemtuzumab). Note: Patients who received B-cell-targeted therapy > 6 and ≤ 12 months prior to randomization must have a B-cell count that is within the laboratory reference range at screening, as measured by the central laboratory. b) Within 1 month: belimumab or any inhibitor of B cell activating factor (BAFF) and/or APRIL, anifrolumab, abatacept, infliximab, adalimumab, certolizumab, golimumab, etanercept, tocilizumab, anakinra, immunoglobulin, blood products, cyclophosphamide IV or oral, live or live-attenuated vaccine, or other biologics with immunomodulating/immunosuppressive activity. c) Within 5 half-lives or 30 days, whichever is longer: any investigational drug.
• Any condition or finding on physical exam, current or previous medical history, vital signs, 12-lead ECG, or laboratory tests that, in the opinion of the investigator or central adjudicator, might interfere with the evaluation of the investigational product or should otherwise exclude a patient.

Other

• Currently enrolled in another interventional clinical study. Note: Patients enrolled in ongoing cohort or non-interventional studies may not donate blood or tissue samples for such studies during their participation in this study (including the Follow-up Period). All the other exclusion criteria can be found in the protocol (section 5.2.2).
• Active severe neuropsychiatric or CNS SLE.

• ≥ 18 to ≤ 70 years of age.
• Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF.
• Diagnosed with SLE at least 24 weeks prior to screening and meets the 2019 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) classification criteria.
• At screening, at least one of the following: a) anti-nuclear antibody (ANA) ≥ 1:80 b) positive anti-dsDNA c) positive anti-Sm
• Patient has all 3 of the following based on features active on the day of the visits: a) hSLEDAI ≥ 6 and clinical hSLEDAI ≥ 4 at screening, and clinical hSLEDAI ≥ 4 at Day 1. Note: Clinical points exclude laboratory tests, except proteinuria. Patients with proteinuria scored as present (i.e., urine protein/creatinine > 500 mg/g) at screening will also be scored as present on Day 1 if a dipstick performed at the site on Day 1 is at least 2+ proteinuria. If the urine protein/creatinine > 500 mg/g at screening is not known to be stable based on recent past proteinuria testing, then a repeat urine protein/creatinine measurement is required during the Screening Period. b) BILAG-2004 Grade A or B in ≥ 1 organ system at screening and Day 1. c) In the opinion of the investigator and the central adjudicator, there is sufficient disease activity to warrant enrollment into a clinical study with an investigational agent.
• Patients must be treated with one or more of the following background nonbiologic lupus standard of care therapies: oral corticosteroid, antimalarial, and/or immunosuppressant. The treatment regimen must be as below: a) If taking oral corticosteroid: No increase in dosing regimen during the Screening Period, and at stable dose ≤ 20 mg/day prednisone-equivalent at least 2 weeks prior to Day 1. b) If taking antimalarial: - No dose increase within 8 weeks prior to the Screening visit. - After the Screening visit (i.e., during the Screening Period and the Treatment Period), dosing must be stable and as follows: hydroxychloroquine ≤ 400 mg/day, quinacrine ≤ 100 mg/day, or chloroquine ≤ 250 mg/day. c) If taking immunosuppressant: - No dose increase within 8 weeks prior to the Screening visit. - After the Screening visit (i.e., during the Screening period and the Treatment period), must be taking no more than 1 immunosuppressant and at a stable dose as follows: mycophenolate mofetil ≤ 3 g/day, mycophenolate sodium ≤ 2160 mg/day, azathioprine ≤ 200 mg/day, 6- mercaptopurine ≤ 100 mg/day, methotrexate ≤ 25 mg/week, cyclosporine ≤ 2 mg/kg/day, tacrolimus ≤ 3 mg/day, or voclosporin ≤ 23.7 mg twice daily.
• Female patient is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: a) Not a woman of childbearing potential (WOCBP) as defined in Appendix 5. OR b) A WOCBP who meets all of the following: - Agrees to either sexual abstinence or use of contraception (as detailed in Appendix 5) until at least 8 weeks after the last administration of IMP. - Has a negative serum pregnancy test at screening and a negative urine pregnancy test at Day 1 prior to the first dose of IMP. - Agrees to refrain from egg donation until at least 8 weeks after the last dose of IMP.
• A male patient is eligible if the following conditions apply: - Agrees to either sexual abstinence or use of contraception (as detailed in Appendix 5) until at least 8 weeks after the last dose of IMP or is surgically sterile. AND Agrees to refrain from donating sperm until at least 8 weeks after the last dose of IMP.