Phase 2 Placebo-Controlled Study to Assess the Safety and Efficacy of ESK-001 in Active Systemic Lupus Erythematosus

Prior treatment

• Clinically significant chronic infection (eg, osteomyelitis, bronchiectasis) within 8 weeks prior to signing the ICF (chronic fungal nail infections are allowed)
• Any infection requiring hospitalization or treatment with IV anti-infectives not completed at least 4 weeks prior to signing the ICF
• Any infection requiring oral anti-infectives (including antivirals) within 2 weeks prior to Day 1
• Any severe herpes infection at any time prior to Week 0 (Day 1), including, but not limited to, disseminated herpes (ever), herpes encephalitis (ever), recurrent herpes zoster (defined as 2 episodes within 2 years), or ophthalmic herpes (ever)
  • Active herpes zoster infection within 12 weeks of prior to signing the ICF
  • Active herpes simplex virus within 4 weeks of Day 1

Other illness

• Drug-induced SLE or other autoimmune diseases that, in the opinion of the Investigator, are likely to confound efficacy assessments
• Current disease other than SLE that, in the opinion of the Investigator, is likely to interfere with SLE disease activity assessments. Examples include severe fibromyalgia, severe osteoarthritis and severe cardiorespiratory diseases.
• Active severe or unstable neuropsychiatric SLE including, but not limited to the following: aseptic meningitis; cerebral vasculitis; myelopathy; demyelination syndromes (ascending or transverse myelitis, acute inflammatory demyelinating polyradiculopathy); acute confusional state; impaired level of consciousness; psychosis; acute stroke or stroke syndrome; cranial neuropathy; new seizures; cerebellar ataxia; and mononeuritis multiplex.
  • That would make the patient unable to fully understand the ICF, or
  • Where, in the opinion of the Principal Investigator, protocol-specified SOC is insufficient and utilization of a more aggressive therapeutic approach not permitted in the protocol, is indicated
• Known history of a primary immunodeficiency or an underlying condition such as HIV infection or splenectomy that predisposes the patient to infection
• Currently active, clinically significant infection of any kind

Other

• Active, proliferative lupus nephritis that in the Investigator's opinion may require treatment not allowed by the protocol
• Other protocol-defined inclusion/exclusion criteria apply

• Patients with 6 or more months of SLE according to the 2019 EULAR/ACR criteria, have positive autoantibodies or low complement at screening, and have active SLE as measured by SLEDAI-2K of 6 or more, or 4 or more if joint involvement is present.
• Patients need to be on treatment which can be:
• A stable dose of oral corticosteroid (≤40 mg/day prednisone or equivalent) for a minimum of 2 weeks prior to signing of the informed consent form (ICF) at the Screening Visit. The dose of oral corticosteroid the patient is taking should not increase between screening and Week 0 (Day 1).
• And/or antimalarial treatment (e.g., hydroxychloroquine, chloroquine, quinacrine),
• And/or no more than 1 of the following conventional DMARDS:
  • Azathioprine ≤200 mg/day
  • Mycophenolate mofetil ≤2 g/day or mycophenolic acid ≤1.44 g/day
  • Oral, subcutaneous, or intramuscular (IM) methotrexate ≤20 mg/week.