Safety and Efficacy of Efavaleukin Alfa in Subjects With Active Rheumatoid Arthritis

Inclusion Criteria: * Subject has provided informed consent prior to initiation of any study specific activities/procedures. * Age ≥ 18 to ≤ 70 years of age at screening. * A diagnosis of RA consistent with the 1987 or 2010 American College of Rheumatology (ACR)/European League Against Rheumatism classification criteria. * Active RA defined as: Phase 1b: DAS-28-CRP \> 2.6 at screening. The 28-joint count consists of the finger joints excluding the distal interphalangeal joints, the wrists, elbows, shoulders, and knees. Phase 2a: ≥ 6 swollen joints (based on 66-joint count) and ≥ 6 tender joints (based on 68-joint count) at screening and baseline. The distal interphalangeal joint should be evaluated but not included in the total count to determine eligibility. Additionally, C-reactive protein (CRP) must be greater than the upper limit of normal (ULN) per the central laboratory at screening. * Receiving treatment with methotrexate for ≥ 12 weeks and on a stable dose ≥ 15 mg weekly for ≥ 8 weeks prior to day 1. A lower methotrexate dose is acceptable (but no lower than 10 mg weekly) if it is the highest tolerated dose and gastrointestinal or hematologic toxicity at doses ≥ 15 mg weekly is documented by the investigator. * Receiving treatment with folic or folinic acid per investigator judgment or according to local standard of care. * Phase 1b only: Subject may be receiving a stable dose of leflunomide, sulfasalazine, hydroxychloroquine, minocycline in combination with methotrexate and the dose must be stable for ≥ 8 weeks prior to day 1. * Subject may be receiving a stable dose of prednisone ≤ 10mg daily or other equivalent corticosteroid dose and the dose must be stable for ≥ 2 weeks prior today 1. * Phase 1b only. Normal or clinically acceptable electrocardiogram (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, seasonal influenza \[during flu season\], and pneumococcal \[polysaccharide\] vaccinations) up to date per local standards as determined by the investigator. Exclusion Criteria: * Class IV RA according to ACR revised response criteria * Diagnosis of Felty's Syndrome (RA, splenomegaly and granulocytopenia). * 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 or sheet provided by Amgen; document 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 deoxyribonucleic acid (DNA) polymerase chain reaction \[PCR\] test) or detectable hepatitis C virus ribonucleic acid (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. * Phase 1b only: Positive for Human Immunodeficiency Virus (HIV) at screening or known to be HIV positive. Phase 2a only: Known history of HIV * Phase 1b only: Positive drug or alcohol urine test for illicit drugs at screening. Prescription medications detected by the drug test are allowed if they are being taken under the direction of a physician. * 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 RA (eg, systemic lupus erythematosus with the exception of secondary Sjögren's syndrome). * Malignancy except non-melanoma skin cancers, cervical or breast ductal carcinoma in situ within the last 5 years. * History of alcohol or substance abuse within 6 months of screening * Phase 1b only: 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, electronic cigarettes, cigarettes, pipes, or nicotine patches. * Phase 1b only: Subject 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. Phase 1b only: Unwilling or unable to abstain from alcohol consumption within 48 hours prior to each visit (including screening). * Subjects who have received intra-articular or systemic corticosteroid injections for treatment of acute RA flare (not being part of a regular therapeutic regimen) within 4 weeks prior to screening. * Currently receiving or had treatment with cyclophosphamide, chlorambucil, nitrogen mustard, or any other alkylating agent ≤ 6 months prior to day 1. * Prior treatment with more than a total of 3 therapies that include biologic disease modifying anti-rheumatic drug (DMARDs) or oral synthetic DMARDs (such as tofacinitib, baricitinib). Prior treatment consists of at least 4 doses of a given therapy where the doses were given solely for treatment of RA disease. Prior therapies must not have been used within the following time periods: * ≤ 4 weeks prior to day 1 for etanercept and anakinra * ≤ 6 months for rituximab * ≤ 2 weeks for oral janus kinase inhibitors * ≤ 9 weeks prior to day 1 for all therapies not listed above * Currently receiving or had treatment with any of the following ≤ 12 weeks prior to day 1: * azathioprine * cyclosporine * gold * mycophenolate mofetil * Prosorba column * Tacrolimus * Phase 2a only: Currently receiving or had treatment with leflunomide ≤ 12 weeks prior to day 1 unless an active washout with cholestyramine has been performed. * Phase 2a only: Currently receiving or had treatment with any of the following ≤ 4 weeks prior to day 1: * hydroxychloroquine * sulfasalazine * minocycline * oral janus kinase inhibitor (eg, tofacitinib, baricitinib) * intra-articular, intramuscular or intravenous corticosteroids, including adrenocorticotropic hormone * intra-articular hyaluronic acid injections * live vaccines -- For Phase 2 only: * Unstable dose of non-steroidal anti-inflammatory drugs (NSAID), acetaminophen, and/or analgesics which is taken on an unscheduled basis (ie, not daily or scheduled every certain number of hours) and/or initiated \<4 weeks prior to day 1. * Received the following within 12 hours prior to screening or day 1: acetaminophen, NSAIDs, tramadol, and/or any narcotic analgesics such as but not limited to hydrocodone, codeine, tramadol, propoxyphene and/or oxycodone (unless in the form of oxycontin). Subject has taken oxycontin within 24 hours prior to screening or day 1. * Phase 1b only: Received any herbal medicines (eg St John's wort),or non-vitamin dietary supplements (eg, magnesium) with the exception of calcium within 4 weeks prior to day 1. * Currently receiving treatment in another investigational device or drug study, or less than 30 days since ending treatment on another investigational device or drug study(ies). Other investigational procedures while participating in this study are excluded. * Presence of laboratory abnormalities at screening including the following: * Aspartate aminotransferase (AST) or alanine amino transferase (ALT) at screening \> 1.5X upper limit of normal (ULN) * Serum total bilirubin (TBL) ≥ 1.5 mg/dL (≥ 26 μmol/L) * Hemoglobin ≤ 10.5 g/dL(≤105 g/L) * Platelet count \< 100,000/mm\^3 (\<100 x 10\^9/L) * White blood cell count \< 2,500 cells/mm\^3 (2.5 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 subject from completing the study, will interfere with the interpretation of the study results, or might cause the study to be detrimental to the subject. * Female subject is pregnant or breastfeeding or planning to become pregnant or breastfeed during treatment and for an additional 6 weeks after the last dose of investigational product. * Females of child-bearing potential with a positive pregnancy test (assessed by a serum pregnancy test at screening and a urine pregnancy test at baseline). * Female subjects of childbearing potential unwilling to use 1 highly effective method of contraception during treatment and for an additional 6 weeks after the last dose of investigational product. * Subject has known sensitivity to any of the products or components to be administered during dosing. * Subject likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures (eg, Clinical Outcome Assessments \[COAs\]) to the best of the subject and investigator's knowledge. * History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures or completion