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