A Study to Evaluate Safety and Efficacy of GSK1278863 in Non-Dialysis Dependent (NDD) Subjects With Anemia Associated With Chronic Kidney Diseases (CKD)

Inclusion Criteria:

- Age: >=18 years of age. (Week -4 verification only)

- Gender: Female and male subjects. (Week -4 verification only) Females: If of
childbearing potential, must agree to use one of the approved contraception methods,
from Screening until completion of the Follow-up Visit OR Of non-childbearing
potential defined as pre-menopausal females with a documented tubal ligation,
hysterectomy, or oophorectomy; or postmenopausal defined as 12 months of spontaneous
amenorrhea. Females on hormone replacement therapy (HRT) whose menopausal status is in
doubt will be required to use one of the approved contraception methods if they wish
to continue their HRT during the study. Otherwise they must discontinue HRT to allow
confirmation of post-menopausal status prior to study enrolment.

- Corrected QT interval (QTc): Bazett's Correction of QT Interval (QTcB) <470
milliseconds (msec) or QTcB <480 msec in subjects with bundle branch block. There is
no QTc criterion for subjects with a predominantly paced rhythm.

- CKD stage: Kidney Disease Outcomes Quality Initiative (KDOQI) CKD stages 3/4/5 defined
by electronic estimated glomerular filtration rate (eGFR) using the CKD Epidemiology
Collaboration (CKD-EPI) formula.

- Hgb: Group 1 (rhEPO naïve): Baseline Hgb of 8.0-11.0 g/dL (inclusive) (USA sites only:
8.0-10.0 g/dL, inclusive); Group 2 (rhEPO users): Baseline Hgb of 9.0-11.5 g/dL
(inclusive) (USA sites only: 9.0-10.5, inclusive).

- Stable rhEPO dose for rhEPO users: Group 2 subjects must be using the same rhEPO
(epoetins or their biosimilars, or darbepoetin) with total weekly doses that varied by
no more than 50% during the 4 weeks prior to Week -4. At Day 1 (randomization),
confirm that total weekly doses varied by no more than 50% during the screening
period.

- Oral iron therapy: If on oral iron, then doses must not be changed for the 4 weeks
prior to Week -4, during the screening phase, and through the first 4 weeks after
Randomization.

Exclusion Criteria:

- Dialysis: On dialysis or planning to initiate dialysis during the study.

- Renal transplant: Pre-emptive or scheduled renal transplant.

- High rhEPO dose: An epoetin dose of >=360 IU/kg/week intravenous (IV) or >=250
IU/kg/week subcutaneous (SC) or darbepoetin dose of >=1.8 microgram per kilogram per
week (mcg/kg/week) IV or SC within the prior 8 weeks through Day 1 (randomization).

- Use of methoxy polyethylene glycol epoetin beta within the prior 8 weeks through Day 1
(randomization).

- IV iron therapy: Use of IV iron for 4 weeks prior to Screening Week -4, during the
screening phase, and through the first 4 weeks after Randomization

- Vitamin B12: Below the lower limit of the reference range (may rescreen in a minimum
of 8 weeks).

- Folate: <2.0 nanogram per millilitre (ng/mL) (<4.5 nanomoles per liter [nmol/L]) (may
rescreen in a minimum of 4 weeks).

- Ferritin: <40 ng/mL (<40 mcg/L).

- Transferrin saturation (TSAT): Below the lower limit of the reference range

- Myocardial infarction or acute coronary syndrome: Within the 8 weeks prior to
Screening through Day 1 (randomization).

- Stroke or transient ischemic attack: Within the 8 weeks prior to Week -4 Screening
through Day 1 (randomization).

- Heart failure: Class III/IV heart failure as defined by the New York Heart Association
(NYHA) functional classification system diagnosed prior to Week -4 Screening through
Day 1 (randomization), symptomatic right heart failure diagnosed prior to Week -4
Screening through Day 1 (randomization).

- Uncontrolled hypertension: Defined as diastolic blood pressure (DBP) >100 mmHg or
systolic blood pressure (SBP) >170 mmHg at Week -4 and reconfirmed at Day 1.

- Thrombotic Disease: History of thrombotic disease (e.g., venous thrombosis such as
deep vein thrombosis or pulmonary embolism, or arterial thrombosis such as new onset
or worsening limb ischemia requiring intervention), except vascular access thrombosis
within the 8 weeks prior to Week -4 Screening through Day 1 (randomization).

- Ophthalmology disease: Meeting any ophthalmologic-related exclusion criteria
determined at the Screening ophthalmology exam.

- Inflammatory disease: Active chronic inflammatory disease that could impact
erythropoiesis (e.g., scleroderma, systemic lupus erythematosis, rheumatoid arthritis,
celiac disease) diagnosed prior to Week -4 Screening through Day 1 (randomization).

- Hematological disease: Any hematological disease including those affecting platelets,
white or red blood cells (e.g. sickle cell anemia, myelodysplastic syndromes,
hematological malignancy, myeloma, hemolytic anemia and thalassemia), coagulation
disorders (e.g., antiphospholipid syndrome, Protein C or S deficiency), or any other
cause of anemia other than renal disease diagnosed prior to Week -4 Screening through
Day 1 (randomization).

- Liver disease: Current liver disease, known hepatic or biliary abnormalities (with the
exception of Gilbert's syndrome or asymptomatic gallstones) or evidence at Screening
of abnormal liver function tests [alanine transaminase (ALT) or aspartate transaminase
(AST) >2.0 x upper limit of normal (ULN) or total bilirubin >1.5 x ULN]; or other
hepatic abnormalities that in the opinion of the investigator would preclude the
subject from participation in the study.

- Major surgery: Major surgery (excluding vascular access surgery) within the prior 8
weeks, during the Week -4 Screening phase or planned during the study.

- Transfusion: Blood transfusion within the prior 8 weeks, during the Week -4 Screening
phase or an anticipated need for blood transfusion during the study.

- Gastrointestinal (GI) Bleeding: Evidence of actively bleeding peptic, duodenal, or
esophageal ulcer disease OR clinically significant GI bleeding within the 8 weeks
prior to Week -4 Screening through Day 1 (randomization).

- Acute infection: Clinical evidence of acute infection or history of infection
requiring IV antibiotic therapy within the 8 weeks prior to Week -4 Screening through
Day 1 (randomization).

- Malignancy: Subjects with a history of malignancy within the prior 5 years, who
receiving treatment for cancer, or who have a strong family history of cancer (e.g.,
familial cancer disorders); with the exception of squamous cell or basal cell
carcinoma of the skin that has been definitively treated prior to Week -4 Screening
through Day 1 (randomization).

- Severe allergic reactions: History of severe allergic or anaphylactic reactions or
hypersensitivity to excipients in the investigational product (see GSK1278863 IB for
list of excipients and rhEPO (refer to local product labelling for details).

- Drugs and supplements: Use of any prescription or non-prescription drugs or dietary
supplements that are prohibited from Week -4 Screening until the Follow-up Visit.

- Prior investigational product exposure: The Subject has participated in a clinical
trial and has received an experimental investigational product within the prior 30
days from Week -4 Screening through Day 1 (randomization).

- Other Conditions: Any other condition, clinical or laboratory abnormality, or
examination finding that the Investigator considers would put the subject at
unacceptable risk.

- Patient participation: Unwillingness or inability of the subject to follow the
procedures or lifestyle or dietary restrictions outlined in the protocol.

- Pregnancy or Lactation: Pregnant females as determined by positive urine human
chorionic gonadotropin (hCG) test OR women who are lactating at Week -4 Screening or
during the trial.