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NCT01977573

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

Completed Phase 2 Results posted Last updated 12 October 2018
What this trial tests

Phase 2 trial testing GSK1278863 in Anaemia in 252 participants. Completed in 15 June 2015.

Timeline
31 October 2013
Primary endpoint
1 May 2015
15 June 2015

Quick facts

Lead sponsorGlaxoSmithKline
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingsingle
Primary purposetreatment
Enrollment252
Start date31 October 2013
Primary completion1 May 2015
Estimated completion15 June 2015
Sites123 locations across Denmark, France, Japan, Russia, Sweden, United Kingdom, Germany, Hungary

Drugs / interventions tested

Conditions studied

Sponsor

GlaxoSmithKline — full company profile →

Who can join

Adults 18 to 99, any sex, with Anaemia. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Summary of Hemoglobin (Hgb) Concentration at Week 24 Primary · Week 24

The original Hgb Criteria for Group 1- rhEPO naive participants with a stable baseline Hgb of 8.0-10.0 g/dL (8.0-10.0 g/dL USA site only) and for Group 2- rhEPO users with a stable baseline Hgb of 9.0-10.5 g/dL (9.0-10.5 g/dL USA site only); the Hgb target range was 9.0 to 10.5 g/dL (9.0-10.5 g/dL USA site only). The study amended Hgb Criteria for Group 1- rhEPO naive participants with a stable baseline Hgb of 8.0-11.0 g/dL and Group 2- rhEPO users with a stable baseline Hgb of 9.0-11.5 g/dL; Hgb target range - 10.0 to 11.5 g/dL. Data are presented for those participants following the original

Original n=45,15,19,13
GroupValue95% CI
rhEPO-Naive GSK127886310.20± 0.906
rhEPO-Naive Control10.64± 0.664
rhEPO-User GSK127886310.03± 0.522
rhEPO-User Control10.66± 0.620
Amended n=61,21,11,17
GroupValue95% CI
rhEPO-Naive GSK127886310.96± 1.044
rhEPO-Naive Control11.05± 1.144
rhEPO-User GSK127886310.42± 0.827
rhEPO-User Control10.86± 1.182
Number of Participants With Hemoglobin (Hgb) in the Target Range at Week 24 Secondary · Week 24

Target range is defined as: Original Hgb Criteria of 9.0 to 10.5 gram/deciliter (g/dL), and Amended Hgb Criteria of 10.0 to 11.5 g/dL. Sites in the USA used 9.0 to 10.5 g/dL.

GroupValue95% CI
rhEPO-Naive GSK127886378
rhEPO-Naive Control20
rhEPO-User GSK127886322
rhEPO-User Control19
Number of Participants Reaching Pre-defined Hgb Stopping Criteria Secondary · Over a period of 24 Weeks

The Hgb stopping criteria was a value of \<7.5 mg/dL obtained on-site via a validated point-of-care Hgb measurement device, which necessitated permanent discontinuation of the study medication. None of the participants met the stopping criteria therefore there is no data to present for this outcome measure.

GroupValue95% CI
rhEPO-Naive GSK12788630
rhEPO-Naive Control0
rhEPO-User GSK12788630
rhEPO-User Control0
Percent Change From Baseline in Hepcidin Concentration at Week 24 Secondary · Baseline and Week 24

Baseline is the last pre-dose hepcidin value. Percent change was calculated as 100 multiplied by (exponential of mean change on log scale minus 1). Change was calculated by subtracting the Baseline value from the Week 24 value.

GroupValue95% CI
rhEPO-Naive GSK1278863-19.27-28.10 – -9.36
rhEPO-Naive Control6.67-13.62 – 31.72
rhEPO-User GSK1278863-9.87-28.59 – 13.76
rhEPO-User Control-17.12-33.22 – 2.86
Maximum Observed Change From Baseline in Serum Erythropoietin (EPO) Secondary · Baseline to Week 24

Blood samples for control arm were collected pre-dose for EPO measurement. Blood samples for GSK1278863 arms were collected on Day 1 (pre-dose ), Week 4 (6-12 hours post-dose ), Week 4 (7-13, 8-14, 9-15, hours post-dose ), Week 8 (pre -dose ), Week 12 (pre -dose ), Week 16 (pre -dose ), Week 20 (pre -dose , 3 hour post-dose ) Week 24 (pre -dose ), and Week 28 (pre -dose ) for EPO measurement. The maximum observed change from baseline in EPO was recorded for each arm. Baseline value for EPO is the pre-dose value on Day 1. Change from Baseline in EPO was calculated as the individual post-baselin

GroupValue95% CI
rhEPO-Naive GSK12788637.27± 12.744
rhEPO-Naive Control27.05± 94.999
rhEPO-User GSK12788633.69± 20.554
rhEPO-User Control25.85± 38.890
Maximum Observed Percent Change From Baseline in Vascular Endothelial Growth Factor (VEGF) Secondary · Baseline and up to Week 24

Blood samples for control arm were collected pre-dose for VEGF measurement. Blood samples for GSK1278863 arms were collected on Day 1 (pre-dose ), Week 4 (6-12 hours post-dose ), Week 4 (7-13, 8-14, 9-15, hours post-dose ), Week 8 (pre -dose ), Week 12 (pre -dose ), Week 16 (pre -dose ), Week 20 (pre -dose , 3 hour post-dose ) Week 24 (pre -dose ), and Week 28 (pre -dose ) for VEGF measurement. The maximum observed change from baseline in VEGF was recorded for each arm . Baseline value for VEGF is the pre-dose value on Day 1. Change from Baseline in VEGF was calculated as the individual post-b

GroupValue95% CI
rhEPO-Naive GSK127886376.3659.46 – 95.06
rhEPO-Naive Control26.841.73 – 58.15
rhEPO-User GSK127886349.9928.28 – 75.39
rhEPO-User Control40.8519.14 – 66.52
Percentage of Time Within, Below, and Above Hemoglobin (Hgb) Target Range, Between Weeks 12 and 24 Secondary · Weeks 12 to 24

The number of days a participant's Hgb was within target range was calculated by estimating (using linear interpolation) the number of days within target range between two scheduled Hgb visits. Percentage of time within range for a participant was calculated by dividing the total number of days that Hgb was within range during Weeks 12 to 24 by the total number of days the participant remained on treatment during Weeks 12 to 24. Similary, percent of time above and below Hgb target range was calculated. Target range was defined as: Original Hgb Criteria of 9.0 to 10.5 g/dL, and Amended Hgb Crit

Percentage of time within target range
GroupValue95% CI
rhEPO-Naive GSK127886368.99± 34.612
rhEPO-Naive Control51.01± 41.403
rhEPO-User GSK127886375.06± 32.485
rhEPO-User Control61.29± 43.352
Percentage of time above target range
GroupValue95% CI
rhEPO-Naive GSK127886322.84± 33.825
rhEPO-Naive Control45.10± 42.579
rhEPO-User GSK127886317.96± 28.809
rhEPO-User Control31.10± 41.683
Percentage of time below target range
GroupValue95% CI
rhEPO-Naive GSK12788638.17± 20.301
rhEPO-Naive Control3.89± 16.175
rhEPO-User GSK12788636.98± 21.118
rhEPO-User Control7.61± 25.113
Change From Baseline in Ferritin Concentration at Week 24 Secondary · Baseline and Week 24

Baseline is the last pre-dose ferritin value. Change was calculated by subtracting the Baseline value from the Week 24 value.

GroupValue95% CI
rhEPO-Naive GSK1278863-30.8± 110.50
rhEPO-Naive Control-2.4± 77.06
rhEPO-User GSK1278863-63.4± 141.93
rhEPO-User Control-20.4± 63.38
Change From Baseline in Transferrin Concentration at Week 24 Secondary · Baseline and Week 24

Baseline is the last pre-dose transferrin value. Change from Baseline in transferrin was calculated by subtracting the Baseline value from the Week 24 value.

GroupValue95% CI
rhEPO-Naive GSK12788630.077± 0.3577
rhEPO-Naive Control-0.008± 0.2694
rhEPO-User GSK12788630.171± 0.4124
rhEPO-User Control0.018± 0.2395
Percent Change From Baseline in Transferrin Saturation at Week 24 Secondary · Baseline and Week 24

Transferrin saturation is measured as a percentage; it is a ratio of serum iron and total iron-binding capacity. Baseline is the last pre-dose transferrin saturation value. Percent change was calculated as 100 multiplied by (exponential of mean change on log scale minus 1). Change was calculated by subtracting the Baseline value from the post-dose value.

GroupValue95% CI
rhEPO-Naive GSK1278863-1.1-8.0 – 6.4
rhEPO-Naive Control12.32.2 – 23.3
rhEPO-User GSK1278863-15.7-26.8 – -3.0
rhEPO-User Control11.4-14.7 – 45.6
Change From Baseline in Total Iron at Week 24 Secondary · Baseline and Week 24

Baseline is the last pre-dose total iron value. Change from Baseline was calculated by subtracting the Baseline value from the Week 24 value.

GroupValue95% CI
rhEPO-Naive GSK12788631.0± 5.01
rhEPO-Naive Control2.5± 5.98
rhEPO-User GSK1278863-1.8± 5.54
rhEPO-User Control0.7± 8.36
Change From Baseline in Total Iron Binding Capacity (TIBC) at Week 24 Secondary · Baseline and Week 24

TIBC measures the blood's capacity to bind iron with transferrin. Baseline is the last pre-dose TIBC value. Change from Baseline in TIBC was calculated by subtracting the Baseline value from the Week 24 value.

GroupValue95% CI
rhEPO-Naive GSK12788633.2± 6.46
rhEPO-Naive Control0.1± 5.17
rhEPO-User GSK12788633.0± 9.44
rhEPO-User Control-1.0± 6.69

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse events (AEs) and serious adverse events (SAEs) were collected from the start of study treatment until the follow-up contact (up to 28 weeks).. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

rhEPO-Naive GSK1278863
Serious: 23/134 (17%)
Deaths:
rhEPO-Naive Control
Serious: 7/45 (16%)
Deaths:
rhEPO-User GSK1278863
Serious: 7/36 (19%)
Deaths:
rhEPO-User Control
Serious: 7/35 (20%)
Deaths:

Serious adverse events (63 terms)

ReactionSystemrhEPO-Naive GSK1278863rhEPO-Naive ControlrhEPO-User GSK1278863rhEPO-User Control
ANY EVENTCardiac disorders
ANY EVENTRenal and urinary disorders
ANY EVENTInfections and infestations
RENAL FAILURE CHRONICRenal and urinary disorders
ANY EVENTMetabolism and nutrition disorders
ANY EVENTVascular disorders
ANY EVENTInvestigations
ANY EVENTPsychiatric disorders
GLOMERULONEPHRITIS CHRONICRenal and urinary disorders
DIABETIC NEPHROPATHYRenal and urinary disorders
RENAL FAILURERenal and urinary disorders
RENAL IMPAIRMENTRenal and urinary disorders
PNEUMONIAInfections and infestations
PYELONEPHRITIS CHRONICInfections and infestations
APPENDICITISInfections and infestations
CELLULITISInfections and infestations
PNEUMONIA PNEUMOCOCCALInfections and infestations
ANGINA PECTORISCardiac disorders
ATRIOVENTRICULAR BLOCK COMPLETECardiac disorders
CARDIAC FAILURE CONGESTIVECardiac disorders
MYOCARDIAL ISCHAEMIACardiac disorders
CARDIAC FAILURECardiac disorders
ANY EVENTGastrointestinal disorders
GASTRIC ULCERGastrointestinal disorders
SMALL INTESTINAL OBSTRUCTIONGastrointestinal disorders
Other adverse events (19 terms — click to expand)

ReactionSystemrhEPO-Naive GSK1278863rhEPO-Naive ControlrhEPO-User GSK1278863rhEPO-User Control
NASOPHARYNGITISInfections and infestations
DIARRHOEAGastrointestinal disorders
NAUSEAGastrointestinal disorders
CONSTIPATIONGastrointestinal disorders
OEDEMA PERIPHERALGeneral disorders
PRURITUSSkin and subcutaneous tissue disorders
HYPERTENSIONVascular disorders
BRONCHITISInfections and infestations
ARTHRALGIAMusculoskeletal and connective tissue disorders
FATIGUEGeneral disorders
EPISTAXISRespiratory, thoracic and mediastinal disorders
AnaemiaBlood and lymphatic system disorders
AstheniaGeneral disorders
CONJUNCTIVITISInfections and infestations
BACK PAINMusculoskeletal and connective tissue disorders
HYPERKALAEMIAMetabolism and nutrition disorders
GOUTMetabolism and nutrition disorders
BLOOD PRESSURE INCREASEDInvestigations
HypoglycaemiaMetabolism and nutrition disorders

Most-reported serious reactions: ANY EVENT, ANY EVENT, ANY EVENT, RENAL FAILURE CHRONIC, ANY EVENT, ANY EVENT, ANY EVENT, ANY EVENT.

Data from ClinicalTrials.gov NCT01977573 adverse events section.

Sponsor's own description

This study will be conducted in approximately 228 subjects with anemia associated with CKD who are not on dialysis. Two groups of subjects will be enrolled into the study: Group 1: recombinant human erythropoietin (rhEPO) naive subjects; Group 2: rhEPO users, who are currently receiving rhEPO. Subjects who are rhEPO naive will be randomized to receive either GSK1278863 once daily (QD) or rhEPO in a 3:1 fashion; subjects who are receiving an rhEPO before enrolling (rhEPO users) will be randomized in a 1:1 fashion to GSK1278863 QD or to the control arm. For those randomized to the control arm, the decision around whether the subject requires rhEPO, the selection of the type of rhEPO (if needed) and the choice of rhEPO dose to achieve and maintain Hgb concentrations within the target range should be based on Investigator clinical judgment, with the historical rhEPO dose and the current Hgb value being considered. The study consists of a screening phase of at least 4 weeks, a 24-week treatment phase and a follow-up visit that will occur approximately 4 weeks after completing treatment. It is anticipated that the data generated will enable selection of the starting dose(s) and optimize dose adjustment regimen(s) for Phase 3 clinical trials.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Targeting hypoxia signalling for the treatment of ischaemic and inflammatory diseases.
    Eltzschig HK, Bratton DL, Colgan SP. · · 2014 · cited 307× · PMID 25359381 · DOI 10.1038/nrd4422
  2. Anaemia in kidney disease: harnessing hypoxia responses for therapy.
    Koury MJ, Haase VH. · · 2015 · cited 245× · PMID 26055355 · DOI 10.1038/nrneph.2015.82
  3. Burden of Anemia in Chronic Kidney Disease: Beyond Erythropoietin.
    Hanna RM, Streja E, Kalantar-Zadeh K. · · 2021 · cited 114× · PMID 33123967 · DOI 10.1007/s12325-020-01524-6
  4. Daprodustat for anemia: a 24-week, open-label, randomized controlled trial in participants with chronic kidney disease.
    Holdstock L, Cizman B, Meadowcroft AM, Biswas N, et al · · 2019 · cited 69× · PMID 30746140 · DOI 10.1093/ckj/sfy013
  5. Role of Hypoxia Inducible Factor-1α (HIF-1α) in Innate Defense against Uropathogenic Escherichia coli Infection.
    Lin AE, Beasley FC, Olson J, Keller N, et al · · 2015 · cited 58× · PMID 25927232 · DOI 10.1371/journal.ppat.1004818
  6. Daprodustat: First Approval.
    Dhillon S. · · 2020 · cited 47× · PMID 32880805 · DOI 10.1007/s40265-020-01384-y
  7. Iron metabolism and management: focus on chronic kidney disease.
    Agarwal AK. · · 2021 · cited 31× · PMID 33777495 · DOI 10.1016/j.kisu.2020.12.003
  8. Profile of Daprodustat in the Treatment of Renal Anemia Due to Chronic Kidney Disease.
    Ishii T, Tanaka T, Nangaku M. · · 2021 · cited 9× · PMID 33628028 · DOI 10.2147/tcrm.s293879

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Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT01977573.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing