4 Week Switch Study in Hemodialysis-dependent Subjects With Anemia Associated With Chronic Kidney Disease
Condition: Anaemia
MeSH terms: Kidney Diseases; Renal Insufficiency, Chronic; Anemia
Study type: Interventional
Phase: Phase 2

Summary: 
      This is a four-week, Phase IIa, randomized, active-controlled, parallel-group, multi-center
      study to evaluate the safety, efficacy and pharmacokinetics of switching subjects from stable
      rhEPO to GSK1278863 in approximately 68 hemodialysis-dependent subjects with anemia
      associated with chronic kidney disease. The study consists of a screening phase of 2 weeks, a
      4-week treatment phase and a 2-week follow-up phase. The range of Hgb values for study
      eligibility is 9.5-12.0 g/dL and the subjects must have received the same rhEPO product with
      total weekly doses that varied by no more than 50% during the 4 weeks prior to the Screening
      visit (Week -1. This study aims to estimate the relationship between dose of GSK1278863 and
      Hgb response in hemodialysis-dependent (HDD) subjects with anemia associated with chronic
      kidney disease after switching from a stable maintenance dose of recombinant human
      erythropoetin (rhEPO).
    

Detailed description: 
      This is a four-week, Phase IIa, randomized, active-controlled, parallel-group, multi-center
      study to evaluate the safety, efficacy and pharmacokinetics of switching subjects from stable
      rhEPO to GSK1278863 in approximately 68 hemodialysis-dependent subjects with anemia
      associated with chronic kidney disease. The study consists of a screening phase of 2 weeks, a
      4-week treatment phase and a 2-week follow-up phase. The range of Hgb values for study
      eligibility is 9.5-12.0 g/dL and the subjects must have received the same rhEPO product with
      total weekly doses that varied by no more than 50% during the 4 weeks prior to the Screening
      visit (Week -1. Eligible subjects, stratified by their prior rhEPO dose will be randomized in
      equal proportions to receive double-blind GSK1278863 0.5 mg, 2 mg or 5 mg QD (after
      discontinuing their rhEPO), or to continue to receive their existing type and dose of rhEPO
      (epoetins or their biosimilars, or darbepoetin). Study treatment will be stopped if Hgb
      values fall outside of the protocol pre-specified ranges. Subject completion is defined as
      completion of all study phases including the follow-up phase.

      This study aims to estimate the relationship between dose of GSK1278863 and Hgb response in
      hemodialysis-dependent (HDD) subjects with anemia associated with chronic kidney disease
      after switching from a stable maintenance dose of recombinant human erythropoetin (rhEPO). In
      addition, the study will characterize the effect of GSK1278863 on various pharmacokinetic
      (PK)/pharmacodynamic (PD) markers, and will investigate the safety and tolerability of
      GSK1278863.

      An early interim analysis of the Hgb data is planned after approximately 20 subjects from
      cohort 1 have completed 3 weeks of treatment. Depending upon the interim findings, a second
      cohort of subjects may be added to investigate an additional GSK1278863 dose arm. Recruitment
      to the first cohort will continue during the interim analysis.

      A second interim analysis is planned after approximately 48 subjects from cohort 1 have
      completed 4 weeks treatment. The purpose of this interim is three-fold, to investigate if a
      second cohort of subjects may be added, to facilitate early development of dose-response and
      PK/PD statistical models, and to generate interim results to facilitate design and dosing
      decisions for the next trial.
    

Intervention name(s): GSK1278863; rhEPO
Intervention type(s): Drug; Drug
Intervention description(s): tablet; injection
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Renal Impairment; Anemia; pharmacokinetics; hemodialysis; Chronic kidney disease; GSK1278863; hemoglobin; Prolyl hydroxylase inhibitor; recombinant human erythropoietin; erythropoiesis stimulating agents; Dialysis, Renal