A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Obexelimab in Patients With Systemic Lupus Erythematosus (Sunstone)

Summary of Study Intervention:

The purpose of this study is to learn if a new investigational drug called Obexelimab can safely help reduce disease activity in adults with lupus. Obexelimab is a bi-specific, inhibitory/noncytolytic monoclonal antibody targeting CD19 & FcyRIIb on B cells; simply put, it is designed to inhibit the activity of B cells, including a subset of plasma cells (which are the cells that produce the majority of antibodies and autoantibodies). Participants will be randomized 1:1 to obexelimab 250 mg or placebo (meaning that there is a 50% chance of receiving the investigational drug) for 24 weeks. The investigational medication is given as two injections under the skin (subcutaneous) once a week, which can be done at home by the patient or a caregiver. The total study duration (Screening, Treatment, and Follow-up) is 40 weeks. Approximately 190 patients will be enrolled in this Zenas Biopharma sponsored study, at approximately 100 sites in approximately 15 countries.

Inclusion/Exclusion Criteria:

Inclusion:

• • ≥ 18 to ≤ 70 years of age.
  • Diagnosed with SLE by a qualified physician at least 24 weeks prior to screening and meets the 2019 EULAR/ACR classification criteria.
  • At screening, at least one of the following:
    • antinuclear antibody (ANA) ≥ 1:80
    • positive anti-dsDNA
    • positive anti-Smith
  • Participant has all 3 of the following based on features active on the day of the visits:
    • hSLEDAI ≥ 6 and clinical hSLEDAI ≥ 4 at screening, and clinical hSLEDAI ≥ 4 at Day 1 (meaning presence of certain specific symptoms within the past months, such as arthritis, myositis, proteinuria, rash, alopecia, ulcers, pericarditis or pleurisy, low complements, anti-double-stranded-DNA, etc).
    • BILAG-2004 Grade A (meaning severe activity) or B (meaning moderate activity) in ≥ 1 organ system at screening and Day 1.
  • Participants must be treated with one or more of the following background nonbiologic lupus standard of care therapies: oral corticosteroid (i.e prednisone), antimalarial (i.e, Plaquenil/hydroxychloroquine), and/or immunosuppressant (i.e, Cellcept/mycophenolate mofetil, Imuran/azathioprine, methotrexate, Lupkynis/voclosporin, etc).
  • Female participants who are women of childbearing potential must agree to use a highly effective form of contraception. Male participants with female partners of childbearing potential must use effective barrier contraception (i.e., condoms) during the study and for at least 120 days after last exposure to study drug. Also, participants may not proceed with sperm or egg donation during the study and for at least 120 days after the last exposure to study drug.

Exclusion:

• • Active lupus nephritis
  • 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.
  • 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.
  • Active severe neuropsychiatric or central nervous system SLE.
  • 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. 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.
  • Major surgery within 4 weeks before screening, or planned surgery during the study.
  • History of relevant allergies, including allergy to study drug or any murine or human-derived protein or immunoglobulin products that could make inclusion in the study inappropriate.
  • Malignancy within 5 years except successfully treated in situ cervical cancer, resected squamous cell or basal cell carcinoma of the skin.
  • History of drug or alcohol abuse in the previous 12 months before screening.
  • Use prior to screening of one or more of the following:

1. 1. Within 6 months: rituximab or similar major B cell-depleting biologic therapy, or T cell-depleting agent such as Campath (alemtuzumab).
   2. Within 1 month: belimumab (Benlysta), anifrolumab (Saphnelo), abatacept (Orencia), infliximab (Remicade), adalimumab (Humira), certolizumab (Simzia), golimumab (Simponi), etanercept (Enbrel), tocilizumab (Actemra), anakinra (Kineret), immunoglobulin (i.e IVIG), blood products (ie blood transfusions, etc), cyclophosphamide intravenous or oral (Cytoxan), live or live-attenuated vaccine, or other biologics with immunomodulating/immunosuppressive activity.
   3. Within 5 half-lives or 30 days, whichever is longer: any investigational drug.

• • Use after the Screening visit of medical treatment (including prescription and non-prescription drugs, biological products, Chinese or herbal medicines, diet supplements, etc.) or health care products that could potentially impact the interpretation of study results.
  • Currently enrolled in another interventional clinical study.
  • Spot urine protein-creatinine ratio > 3.0 mg/mg (339 mg/mmol) or estimated glomerular filtration (eGFR) rate < 30 mL/min/1.73 m2 at screening.
  • Body mass index < 18 or > 40.0 kg/m2.
  • Acute hepatitis B infection (hepatitis B surface antigen-positive), active hepatitis C virus, or HIV infection. Participants will be excluded from the study if they have a positive test for active hepatitis B through detection of (a) hepatitis B surface antigen or (b) hepatitis B core antibody.
  • Evidence of active tuberculosis (TB) or at high risk for TB.
  • Bacteria, mycobacteria, virus, systemic fungi, parasites, or opportunistic infection that are not resolved within 14 days before randomization.
  • Alanine aminotransferase ≥ 2.5 × upper limit of normal (ULN) or aspartate aminotransferase ≥ 2.5 × ULN; total bilirubin ≥ 1.5 × ULN at screening.
  • Total white blood cell count < 2,000/μL; absolute neutrophil count < 1,500/μL; platelet count < 50,000/μL; hemoglobin < 9.0 g/dL, at screening.
  • History or evidence of comorbidities that would pose a risk to patient safety.

Contact Information for the Study:

Christele Felix

felixc@hss.edu

646.714.6196