Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Immunogenicity of Efavaleukin Alfa in Participants With Systemic Lupus Erythematosus

Inclusion Criteria: Participants are eligible to be included in the study only if all of the following criteria apply: * Participant has provided informed consent prior to initiation of any study specific activities/procedures. * Age ≥ 18 years to ≤ 70 years at screening. * Fulfills diagnostic criteria for SLE according to the Systemic Lupus International Collaborating Clinics (SLICC) criteria or by at least 4 of the 11 criteria of the 1997 American College of Rheumatology (ACR) classification criteria for SLE, with a history of at least one of the following: * Antinuclear antibody ≥ 1:80; or * Elevated anti-dsDNA antibodies * May be taking ≤ 3 systemic SLE treatments and the dose must be stable for ≥ 4 weeks prior to day 1. * Prednisone dose ≤ 20 mg daily (or other equivalent oral corticosteroid) with stable dose ≥ 2 weeks prior to day 1. * Normal or clinically acceptable ECG values (12-lead reporting ventricular rate and PR, QRS, QT and QTc interval) at screening and baseline based on opinion of the investigator. * Immunizations (tetanus, diphtheria, pertussis \[Td/Tdap\]), seasonal influenza (during flu season), and pneumococcal (polysaccharide) vaccinations\] up to date per local standards as determined by the investigator. Exclusion Criteria: Participants are excluded from the study if any of the following criteria apply. Disease Related \- History of lupus nephritis requiring induction therapy and/or lupus cerebritis ≤ 1 year prior to screening. Other Medical Conditions * Diagnosis of inflammatory joint or skin disease other than SLE which would interfere with SLE disease assessment based on investigator judgement. * Diagnosis of fibromyalgia which would interfere with SLE assessment according to the investigator. * Prosthetic joint infection within 3 years of screening or native joint infection within 1 year prior to screening. * Active infection (including chronic or localized infections) for which anti-infectives were indicated within 4 weeks prior to day 1 OR presence of serious infection, defined as requiring hospitalization or intravenous anti-infectives within 8 weeks prior to day 1. * Known history of active tuberculosis. * Positive test for tuberculosis during screening defined as either: * positive purified protein derivative (PPD) (≥ 5 mm of induration at 48 to 72 hours after test is placed) OR positive Quantiferon test * a positive PPD and a history of Bacillus Calmette-Guérin vaccination are allowed with a negative Quantiferon test and negative chest X-ray. * a positive PPD test (without a history of Bacillus Calmette-Guérin vaccination) or a positive or indeterminate Quantiferon test are allowed if they have ALL of the following at screening: * no symptoms per tuberculosis worksheet provided by Amgen * documented history of a completed course of adequate prophylaxis (completed treatment for latent tuberculosis per local standard of care prior to the start of investigational product) * no known exposure to a case of active tuberculosis after most recent prophylaxis * negative chest X-ray. * Positive for hepatitis B surface antigen, hepatitis B core antibody (confirmed by hepatitis B DNA polymerase chain reaction \[PCR\] test) or detectable hepatitis C virus RNA by PCR (screening is generally done by hepatitis C antibody \[HepCAb\], followed by hepatitis C virus RNA by PCR if HepCAb is positive). A history of hepatitis B vaccination without history of hepatitis B is allowed. * Positive for Human Immunodeficiency Virus (HIV) at screening, or known to be HIV positive. * Presence of one or more significant concurrent medical conditions per investigator judgment, including but not limited to the following: * poorly controlled diabetes or hypertension * chronic kidney disease stage IIIb, IV, or V * symptomatic heart failure (New York Heart Association class II, III, or IV) * myocardial infarction or unstable angina pectoris within the past 12 months prior to randomization * severe chronic pulmonary disease (eg, requiring oxygen therapy) * multiple sclerosis or any other demyelinating disease * major chronic inflammatory disease or connective tissue disease other than SLE (eg, RA). * Malignancy except non-melanoma skin cancers, cervical or breast ductal carcinoma in situ within 5 years of screening. * Participants with a urine test positive for illicit drugs or alcohol at the screening visit. Prescription medications detected by the drug test are allowed if they are being taken under the direction of a physician. * History of alcohol or substance abuse within 6 months of screening. * Current smoker, and/or use of any nicotine or tobacco containing products within the last 6 months prior to day 1. These types of products include but are not limited to: snuff, chewing tobacco, cigars, cigarettes, electronic cigarettes, pipes, or nicotine patches. * Participant unwilling to limit alcohol consumption to ≤ 1 drink of alcohol per day and ≤3 drinks per week for the duration of the study, where a drink is equivalent to 12 ounces of regular beer, 8 to 9 ounces of malt liquor, 5 ounces of wine, or 1.5 ounces of 80 proof distilled spirits. Prior/Concomitant Therapy * Currently receiving or had treatment with: cyclophosphamide, chlorambucil, nitrogen mustard, or any other alkylating agent ≤ 6 months prior to day 1 OR oral calcineurin inhibitors (eg, cyclosporine, tacrolimus, sirolimus) ≤ 4 weeks prior to day 1. * Current or previous treatment for SLE with a biologic agent as follows: rituximab \< 6 months prior to day 1, belimumab \< 3 months prior to day 1, abatacept \< 8 weeks prior to day 1. * Currently receiving or had treatment with T cell depleting agents (eg, antithymocyte globulin, Campath) or recombinant IL-2 (eg, Proleukin). * Participants who have received intra-articular or systemic corticosteroid injections within 4 weeks prior to day 1 or topical steroids within 2 weeks prior to day 1. * Administration of herbal supplements, vitamins, or nutritional supplements within 30 days prior to the first dose of investigational product, and continuing use, if applicable, will be reviewed by the Investigator and the Amgen Medical Monitor to determine acceptability. Written documentation of this review and Amgen acknowledgment is required for participant participation. Prior/Concurrent Clinical Study Experience * Currently receiving treatment in another investigational device or drug study, or less than 30 days at day 1 since ending treatment on another investigational device or drug study(ies). Other investigational procedures while participating in this study are excluded. * Participant previously enrolled in this study may not be re-enrolled unless they fulfill the following criteria: * Have completed the study previously without any adverse events deemed related to study drug. * Have received the last dose of Efavaleukin Alfa/placebo \> 6 months prior to the screening visit. * Must not have tested positive for neutralizing antibodies against Efavaleukin Alfa at any time. Diagnostic Assessments * Presence of laboratory abnormalities at screening including the following: * Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \> 1.5x upper limit of normal (ULN) * Serum total bilirubin (TBL) ≥ 1.5 mg/dL (≥ 26 μmol/L) * Hemoglobin \< 9.0 g/dL(\< 90 g/L) * Platelet count \< 100,000/mm\^3 (100 x 10\^9/L) * White blood cell count \< 2,000 cells/mm\^3 (2.0 x 10\^9/L) * Absolute neutrophil count (ANC) \< 1,000/mm\^3 (1.0 x 10\^9/L) * Calculated glomerular filtration rate of ≤ 50 mL/min/1.73 m\^2 using the Modification of Diet in Renal Disease (MDRD) formula. * Any other laboratory abnormality, which, in the opinion of the investigator, poses a safety risk, will prevent the participant from completing the study, will interfere with the interpretation of the study results, or might cause the study to be detrimental to the participant.