Anemia associated with chronic kidney disease. MedDRA version: 14.1 Level: LLT Classification code 10064848 Term: Chronic kidney disease System Organ Class: 100000004857
Conditions
Sponsors
GlaxoSmithKline, S.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects are eligible if they meet all of the inclusion criteria below. Generalcriteria (Week -4 verification only) 1.Age: >18 years of age. 2.Gender: Female and male subjects. ? Females: If of childbearing potential, must agree to use one of the approved contraception methods as outlined in Section 11.5 from Screening until completion of the Follow-up Visit OR Of non-childbearing potential defined a pre-menopausal females with a documented tubal ligation, hysterectomy , or oophorectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) 23.0-116.3 IU/L and estradiol or=1.2 based on a historical value obtained within the prior month in order to ensure the adequacy of dialysis. If Kt/Vurea is not available, then an average of the last 2 values of urea reduction ratio (URR) of at least 65%. NOTE: Only needs confirming at Week -4. 6. Hemoglobin: Baseline Hgb of 9.0-11.5 g/dL as outlined in Section 4.2 (may rescreen in a minimum of 2 weeks). 7. Stable rhEPO dose: Using the same rhEPO (epoetins or their biosimilars, or darbepoetin) with total weekly doses varying by no more than 50% during the 4 weeks prior to Week -4. At Day 1 (randomization), confirm that total weekly dose varied by no more than 50% during the screening period. 8. Iron replacement therapy: Subjects may be on stable maintenance oral or IV (=65 years) yes F.1.3.1 Number of subjects for this age range 30
Exclusion criteria
Exclusion criteria: Subjects are not eligible if they meet any criteria below. CKD-relatedcriteria 1.Dialysis modality:Planned change from HD to peritoneal dialysis within the study time period. 2.Renal transplant:Pre-emptive or scheduled renal transplant. 3.High rhEPO dose:An epoetin dose of >or=360 IU/kg/week IV or darbepoetin dose of >or=1.8 µg/kg/week IV within the prior 8 weeks through Day 1 (randomization). 4.Mircera:Use of Mircera (methoxy polyethylene glycol epoetin beta) within the prior 8 weeks through Day 1 (randomization). Laboratorytest-based criteria (Week -4 verification only) 5.Vitamin B12: At or below the lower limit of the reference range (may rescreen in a minimum of 8 weeks). 6.Folate: 100 mmHg or SBP >170 mmHg. 13.Thrombotic disease:History of thrombotic disease, except vascular access thrombosis, within the 8 weeks prior to Week -4 Screening through Day 1 (randomization). Other disease-relatedcriteria 14.Ophthalmology disease:Meeting any ophthalmologic-related exclusion criteria determined at the Screening ophthalmology exam as outlined in Section 11.6. 15.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). 16.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 or any other cause of anemia other than renal disease diagnosed prior to Week -4 Screening through Day 1 (randomization). 17.Liver disease:Current liver disease, known hepatic or biliary abnormalities or evidence at Screening of abnormal liver function tests or other hepatic abnormalities that in the opinion of the investigator would preclude the subject from participation in the study. 18.Major surgery:Major surgery (excluding vascular access surgery) within the prior 8 weeks, during the Week -4 Screening phase or planned during the study. 19.Transfusion:Blood transfusion within the prior 8 weeks, during the Week -4 Screening phase or an anticipated need for blood transfusion during the study. 20.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). 21.Acute infection: Clinical evidence of acute infection or history of infection requiring intravenous (IV) antibiotic therapy within the 8 weeks prior to Week -4 Screening through Day 1 (rando
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Characterize the dose-response relationship between GSK1278863 and Hgb at Week 4.;Secondary Objective: -Characterize the ability of GSK1278863 to achieve Hgb within the target range (10.0 to 11.5 g/dL). -Characterize the effect of GSK1278863 on measures of iron metabolism and utilization, on indices of hematopoiesis, EPO and on Vascular Endothelial Growth Factor (VEGF) -Characterize the steady-state population pharmacokinetic (PK) of GSK1278863 and metabolites. -Assess the safety and tolerability of GSK1278863 following once daily (QD) administration for 24 weeks.;Primary end point(s): Hemoglobin change from baseline at Week 4;Timepoint(s) of evaluation of this end point: Week 4 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Hgb change from baseline at Week 24 - Percentage of time within, below, and above target range between Week 20 and 24 - Number (%) of subjects with Hgb in the target range at Week 24 - Change from baseline in hepcidin, ferritin, transferrin, transferrin saturation, total iron, total iron binding capacity (TIBC), reticulocyte Hgb (CHr), %hypochromic red blood cells (RBCs) at Week 24 - Change from baseline in hematocrit, RBC, reticulocyte number at Week 24 - Maximum observed change from baseline in EPO - Maximum observed change from baseline in VEGF - Population plasma PK parameters of GSK1278863 and metabolites - Incidence and severity of adverse events (AE)s and serious AEs (SAEs) - Reasons for discontinuation of study drug - Discontinuation for safety-related reasons, e.g. pre-specified stopping criteria or AE - Absolute values and changes from baseline in laboratory parameters, systolic pulmonary artery pressure (sPAP) left ventricular ejection fraction (LVEF), ophthalmology assessments, and vital signs - Preliminary assessment of major adverse cardiovascular events (MACE) and other cardiovascular (CV) events;Timepoint(s) of evaluation of this end point: week 24 | — |
Countries
Australia, Canada, Czech Republic, Denmark, France, Hungary, Japan, Korea, Republic of, Russian Federation, Spain, Sweden, United Kingdom, United States
Contacts
Public ContactClinical Trials Helpdesk
GlaxoSmithKline Research & Development Ltd
Outcome results
None listed