Efficacy and Safety of Efavaleukin Alfa in Subjects With Active Systemic Lupus Erythematosus

A Phase 2b Dose Ranging Study to Evaluate the Efficacy and Safety of Efavaleukin Alfa in Subjects With Active Systemic Lupus Erythematosus With Inadequate Response to Standard of Care Therapy

The primary objective is to evaluate the efficacy and safety of efavaleukin alfa in subjects with active systemic lupus erythematosus.

Inclusion Criteria:

• Participant has provided informed consent prior to initiation of any study specific activities/procedures.
• Participant is aged between 18 and 75.
• Fulfills classification criteria for systemic lupus erythematosus (SLE) according to the 2019 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) classification criteria for SLE with antinuclear antibody ≥ 1:80 by immunofluorescence on Hep-2 cells being present at screening.
• Hybrid SLEDAI score ≥ 6 points with a "Clinical" hSLEDAI score ≥ 4 points. The "Clinical" hSLEDAI is the hSLEDAI assessment score without the inclusion of points attributable to laboratory results, including urine or immunologic parameters.
• British-Isles Lupus Assessment Group (BILAG) index score (BILAG 2004) of ≥ 1 A item or ≥ 2 B items.
• Must be taking ≥ 1 of the following SLE treatments (or regional equivalent): hydroxychloroquine, chloroquine, quinacrine, mycophenolate mofetil, azathioprine, methotrexate, dapsone, or oral calcineurin inhibitors, or OCS. A participant may enter the study on OCS alone (prednisone ≥ 10 mg/day or equivalent) only if the participant has previously documented trial of anti-malarial or immunosuppressant treatment for SLE. Participants must be on a stable dose for ≥ 8 weeks prior to screening for all antimalarials and immunosuppressants, with the exception of OCS doses which must be stable for ≥ 2 weeks prior to screening.
• For participants taking OCS, dose must be ≤ 20 mg/day of prednisone or OCS equivalent, and the dose must be stable at baseline visit and for ≥ 2 weeks prior to screening visit.
• Stability of SLE treatments: OCS and other immunosuppressants/immunomodulator agents and doses must be stable since screening visit.
• Disease activity: active disease as indicated by clinical hSLEDAI score ≥ 4 must be observed (clinical hSLEDAI score is the hSLEDAI assessment score without the inclusion of points attributable to laboratory results including urine and immunologic parameters).

Exclusion Criteria:

• Lupus nephritis if any of the following are present: urine protein creatinine ratio ≥ 2000 mg/g (or equivalent) at screening, OR requiring induction therapy currently or within 1 year prior to screening, OR histological evidence (if available) of diffuse proliferative glomerulonephritis within 12 weeks prior to screening.

• Active CNS lupus within 1 year prior to screening including, but not limited to, aseptic meningitis, ataxia, CNS vasculitis, cranial neuropathy, demyelinating syndrome, optic neuritis, psychosis, seizures, or transverse myelitis.

• Currently present or within 1 year prior to screening a diagnosis of any chronic inflammatory disease other than SLE (eg, rheumatoid arthritis) which would interfere with SLE disease assessment.

• History of any disease other than SLE that has required treatment with oral or parenteral corticosteroids for > 2 weeks within 4 months prior to screening.

• Active infection (including chronic or localized infections) for which anti-infectives are indicated currently or within 4 weeks prior to screening visit OR presence of serious infection, defined as requiring hospitalization or intravenous anti-infectives within 8 weeks prior to screening visit.

• Active tuberculosis or latent tuberculosis with no documented past history of adequate treatment per local standard of care.

• Positive test for tuberculosis during creening defined as: either a positive or indeterminate QuantiFERON®-TB or T-spot test OR positive purified protein derivative (PPD) (≥5 mm of induration at 48 to 72 hours after test is placed).

• Positive for hepatitis B surface antigen (HBsAg); or positive for hepatitis B core antibody (HBcAb). A history of hepatitis B vaccination without history of hepatitis B infection (ie, positive hepatitis B surface antibody (HBsAb), negative HBsAg and negative HBcAb) is allowed.

• Positive for hepatitis C antibody.

• Known history of HIV or positive HIV test at screening.

• Presence of 1 or more significant concurrent medical conditions, including but not limited to the following:

  • poorly controlled diabetes (hemoglobin A1C > 7) or hypertension
  • symptomatic heart failure (New York Heart Association class III or IV)
  • myocardial infarction or unstable angina pectoris within the past 12 months prior to screening
  • severe chronic pulmonary disease requiring oxygen therapy
  • multiple sclerosis or any other demyelinating disease

• Any history of malignancy with the following exceptions:

• resolved non-melanoma skin cancers > 5 years prior to screening

• resolved cervical carcinoma > 5 years prior to screening

• resolved breast ductal carcinoma in situ > 5 years of screening

• Currently receiving or had treatment with: cyclophosphamide, chlorambucil, nitrogen mustard, or any other alkylating agent within 6 months prior to screening or sirolimus within 4 weeks prior screening.

• Currently receiving or had treatment with a Janus kinase (JAK) inhibitor within 3 months or less than 5 drug half-lives (whichever is longer) prior to screening.

• Currently receiving or had treatment with an immune checkpoint inhibitor (eg, programmed death 1 [PD-1] inhibitor, programmed death ligand 1 [PD-L1] inhibitor, cytotoxic T-lymphocyte associated protein 4 [CTLA-4] inhibitor).

Note: Abatacept is not considered a CTLA-4 inhibitor and is referred to below.

• Currently receiving or had treatment within 12 months prior to screening with T-cell depleting agents (eg, antithymocyte globulin, Campath).
• Currently receiving of had treatment with an interleukin 2 (IL-2) based therapy (eg, Proleukin).
• Current or previous treatment with a biologic agent with immunosuppressive/immunomodulatory activity as follows: rituximab within 6 months prior to screening; abatacept and belimumab within the past 3 months prior to screening; other biologics within < 5 drug half lives prior to screening.
• Participants who have received intraarticular, intralesional, or intramuscular corticosteroids within 2 weeks prior to screening or intravenous corticosteroids within 6 weeks prior to screening.
• Participants who have received live vaccines within 5 weeks prior to screening, or plan to receive live vaccines during the treatment period and up to 6 weeks after the end of treatment period in the study.
• Currently receiving treatment in another investigational device or drug study.
• Ending a treatment with an investigational drug or investigational device less than 3 months or 5 half-lives from the last dose of the investigational drug (whichever is longer) at screening.