Safety and Efficacy of AMG 592 in Subjects With Active Systemic Lupus Erythematosus

Inclusion Criteria:

Subjects are eligible to be included in the study only if all of the following criteria
apply:

- 101 Subject has provided informed consent prior to initiation of any study specific
activities/procedures.

- 102 Age ≥ 18 years to ≤ 60 years at screening.

- 103 Fulfils 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 at least
one of the following being present at screening:

- Antinuclear antibody ≥ 1:80; or

- Elevated anti-dsDNA antibodies

- 104 Phase 2a Subjects Only: At least one of the following at screening:

- SLEDAI 2K ≥ 6 without including anti-dsDNA or C3 and C4 complement toward the total
score. If a subject qualifies for the study by scoring for arthritis on the SLEDAI 2K
form, they must have ≥ 3 swollen and/or tender joints; or

- CLASI score ≥10

- 105 Phase 2a Subjects Only: Meets SLE diagnostic and severity requirements per Central
Review team at screening

- 106 Phase 2a Subjects Only: Taking at least 1 but not more than 3 of the following SLE
treatments: mycophenolate mofetil, azathioprine, methotrexate, hydroxychloroquine,
chloroquine, dapsone (confirmed by blood specific drug levels) or quinacrine. Subjects
must be on SLE treatment for ≥ 12 weeks and have a stable dose for ≥ 4 weeks prior to
day 1.

- 107 Phase 1b Subjects only: May be taking ≤ 3 systemic SLE treatments and the dose
must be stable for ≥ 4 weeks prior to day 1.

- 108 Prednisone dose ≤ 20 mg daily (or other equivalent oral corticosteroid) with
stable dose ≥ 2 weeks prior to day 1

- 109 Phase 1b Subjects Only: 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.

- 110 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:

- Subjects are excluded from the study if any of the following criteria apply. Disease
Related

- 201 History of lupus nephritis requiring induction therapy and/or lupus cerebritis ≤ 1
year prior to screening

- 202 Phase 2a only: Spot urine protein to creatinine ratio > 2 mg/g at screening Other
Medical Conditions

- 203 Diagnosis of inflammatory joint or skin disease other than SLE which would
interfere with SLE disease assessment based on investigator judgement.

- 204 Diagnosis of fibromyalgia which would interfere with SLE assessment according to
the investigator

- 205 Prosthetic joint infection within 3 years of screening or native joint infection
within 1 year prior to screening.

- 206 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.

- 207 Known history of active tuberculosis

- 208 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

- 209 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.

- 210 Phase 1b Subjects Only: Positive for Human Immunodeficiency Virus (HIV) at
screening, or known to be HIV positive Phase 2a Subjects Only: Known history of HIV

- 211 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)

- 212 Malignancy except non-melanoma skin cancers, cervical or breast ductal carcinoma
in situ within 5 years of screening

- 213 Positive drug or alcohol urine test at screening

- 214 History of alcohol or substance abuse within 6 months of screening 215 Phase 1b
Subjects 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, cigarettes, electronic cigarettes,
pipes, or nicotine patches.

- 216 Phase 1b Subjects 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.

Prior/Concomitant Therapy

- 217 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.

- 218 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.

- 219 Currently receiving or had treatment with T cell depleting agents (eg,
antithymocyte globulin, Campath) or recombinant IL-2 (eg, Proleukin).

- 220 Subjects 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.

- 221 Phase 1b Subjects only: 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 subject participation.

Prior/Concurrent Clinical Study Experience

- 222 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.

- 223 Subject previously enrolled in this study Diagnostic Assessments

- 224 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/mm3 (100 x 109/L)

- White blood cell count < 3,000 cells/mm3 (3.0 x 109/L)

- Absolute neutrophil count (ANC) < 1,500/mm3 (1.5 x 109/L)

- Calculated glomerular filtration rate of ≤ 50 mL/min/1.73 m2 using the Modification of
Diet in Renal Disease (MDRD) formula

- 225 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.