AnaemiaPhase 2NCT01587924
4 Week Switch Study in Hemodialysis-dependent Subjects With Anemia Associated With Chronic Kidney Disease
A Phase 2 study testing GSK1278863 and rhEPO in people with Anaemia, run by GlaxoSmithKline at 62 sites in 6 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Anaemia
- What is being tested?
- GSK1278863 and rhEPO
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 62 sitesin 6 countries
- Study dates
- 23 May 2012to 27 May 2013
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age and weight: >/=18 years of age and >/=45 kg (weight post-dialysis).
- On three times weekly hemodialysis for at least 8 weeks, irrespective of eGFR values and stage of chronic kidney disease (CKD).
- A single-pool Kt/Vurea of >/=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%.
- rhEPO use: Using the same rhEPO (epoetins or darbepoetin) with total weekly doses that varied by no more than 50% during the prior 4 weeks (i.e., maximum vs. minimum total weekly doses </=50%).
- Hgb concentrations 9.5-12.0 g/dL (inclusive).
- Vitamin B12 above the lower limit of the reference range (may rescreen in two months).
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- Folate: >/= 2.0 ng/mL (may rescreen in one month).
- Ferritin: >/=40 ng/mL with the absence of microcytic or hypochromic RBCs.
- Transferrin saturation (TSAT): Within the reference range.
- Iron replacement therapy: Stable maintenance dose of oral iron replacement therapy, if required, that will be maintained throughout the study. NOTE: IV iron replacement therapy is not allowed the two weeks prior to Screening through the end of the study (Week 6).
- QTc: QTcB <470 msec or QTcB <480 msec in subjects with bundle branch block obtained at Screening Visit (based on Central Reader's interpretation).
- Females: Eligible to participate if she is of childbearing potential, and 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 of hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH)>40MIU/ml and estradiol <40pg/ml is confirmatory]. 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. For most forms of HRT, at least 2 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method.
- Males: Must agree to use one of the approved contraceptive methods from the time of Screening until completion of the Follow-up Visit.
Who cannot join
- Dialysis modality: On peritoneal dialysis OR planned change in dialysis modality within the study time period.
- rhEPO Hyporesponders: As defined by an epoetin dose of >/=360 IU/kg/week IV or darbepoetin dose of >/=1.8 µg/kg/week IV within the prior 8 weeks.
- Renal transplant: Renal transplant anticipated or scheduled within the study time period or subjects with a functioning renal transplant.
- Mircera or Peginesatide: Current or prior use (within the prior 8 weeks) of Mircera (methoxy polyethylene glycol epoetin beta) OR peginesatide.
- Total CPK: >5x the upper limit of the reference range.
- HIV: Positive HIV antibody.
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- History of myocardial infarction or acute coronary syndrome within the prior 6 months.
- History of stroke or transient ischemic attacks (TIAs) within the prior 6 months.
- Heart failure: Class III/IV heart failure, as defined by the New York Heart Association (NYHA) functional classification system.
- Hypertension: Poorly controlled hypertension, whether due to inadequate treatment, or lack of treatment, is defined as follows:
- DBP >100 mmHg or SBP>160 mmHg for subjects taking hypertension medication(s) before screening and dialysis, if required.
- DBP >105 mmHg or SBP>170 mmHg for subjects who are asked to hold hypertension medication(s) before screening and dialysis.
- 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), or other thrombosis related condition except shunt thrombosis) within the prior 6 months.
- Pulmonary hypertension: Known pulmonary hypertension and those at higher risk (than normally associated with CKD) for pre-existing elevation in pulmonary pressure (e.g., significant heart failure or lung disease requiring supplemental oxygen, or those with connective tissue diseases).
- Inflammatory disease: Chronic inflammatory disease that could impact erythropoiesis (e.g., scleroderma, systemic lupus erythematosis, rheumatoid arthritis, celiac disease).
- Haematological disease: Any haematological disease including those affecting platelets, the coagulation disorders (e.g., Protein C or S deficiency) or red blood cells (e.g. sickle cell anemia, myelodysplastic syndromes, haematological malignancy, myeloma, haemolytic anemia) or any other cause of anemia other than renal disease.
- 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 [alkaline phosphatase, 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: (excluding vascular access surgery) Within the prior 12 weeks or planned during the study.
- Transfusion: Blood transfusion within the prior 12 weeks or an anticipated need for blood transfusion during the study.
- Ulcer and Active GI Bleeding: Evidence of active peptic, duodenal, or esophageal ulcer disease OR GI bleeding within the prior 12 weeks.
- Acute infection: Clinical evidence of acute infection or history of infection requiring intravenous (IV) antibiotic therapy the eight weeks prior to Screening through Day 1 (randomization).
- Malignancy: History of malignancy within the prior 5 years or are receiving treatment for cancer or those with 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.
- Eyes: History of proliferative retinopathy requiring treatment within the prior 12 months or macular edema requiring treatment.
- Severe reactions: History of severe allergic or anaphylactic reactions or hypersensitivity to excipients in the investigational product.
- Drugs and supplements: Use of any prescription or non-prescription drugs or dietary supplements that are prohibited from Screening until the Follow-up Visit.
- Androgens: New androgen therapy or changes to pre-existing androgen regimen within the prior 12 weeks.
- Prior investigational product exposure: The Subject has participated in a clinical trial and has received an experimental investigational product within the prior 30 days.
- Protocol compliance: Unwillingness or inability to follow the procedures, or lifestyle and/or dietary restrictions outlined in the protocol.
- Other Conditions: Any condition which in the investigator's opinion should exclude the subject from participating in the study.
- Pregnancy or Lactation: Pregnant females as determined by positive serum hCG test OR women who are lactating at Screening or during the trial.
Trial locations and contacts
62 sites in 6 countries.
62 sites in 6 countries
United States42 sites
GSK Investigational Site
Arlington, Texas, 76011
GSK Investigational Site
Arvada, Colorado, 80002
GSK Investigational Site
Asheville, North Carolina, NC 28805
GSK Investigational Site
Azusa, California, 91702
GSK Investigational Site
Bakersfield, California, 93308
GSK Investigational Site
Bakersfield, California, 93309
GSK Investigational Site
Bethesda, Maryland, 20814
GSK Investigational Site
Brooklyn, New York, 11212
GSK Investigational Site
Charlotte, North Carolina
GSK Investigational Site
Coral Springs, Florida, 33071
GSK Investigational Site
Denver, Colorado, 80230
GSK Investigational Site
Detroit, Michigan, 48236
GSK Investigational Site
Durham, North Carolina, 27704
GSK Investigational Site
Erie, Pennsylvania, 16507
GSK Investigational Site
Greenville, Texas, 75402
GSK Investigational Site
Gurnee, Illinois, 60031
GSK Investigational Site
Houston, Texas, 77004
GSK Investigational Site
Houston, Texas, 77091
GSK Investigational Site
Killeen, Texas, TX 76543
GSK Investigational Site
Las Vegas, Nevada, 89106
GSK Investigational Site
Los Angeles, California, 90022
GSK Investigational Site
Los Angeles, California, 90025-4837
GSK Investigational Site
Los Angeles, California, 90057
GSK Investigational Site
Lynwood, California, 60262
GSK Investigational Site
Macon, Georgia, 31217
GSK Investigational Site
Miami, Florida, 33145
GSK Investigational Site
Miami, Florida, 33150
GSK Investigational Site
Oklahoma City, Oklahoma, 73116
GSK Investigational Site
Orange, California, 92868
GSK Investigational Site
Paragould, Arizona, 72450
GSK Investigational Site
Pembroke Pines, Florida, 33028
GSK Investigational Site
Pine Bluff, Arkansas, 71603
GSK Investigational Site
Riverside, California, 92505
GSK Investigational Site
San Antonio, Texas, 78229
GSK Investigational Site
Southgate, Michigan, 48195
GSK Investigational Site
Spring Hill, Florida, 34608
GSK Investigational Site
Tempe, Arizona, 85284
GSK Investigational Site
Waterbury, Connecticut, 06708
GSK Investigational Site
West Hills, California, 91307
GSK Investigational Site
Westminster, Colorado, 80031
GSK Investigational Site
Whittier, California, 90603
GSK Investigational Site
Winston-Salem, North Carolina, 27101
Germany7 sites
GSK Investigational Site
Aschaffenburg, Bavaria, 63741
GSK Investigational Site
Cologne, North Rhine-Westphalia, 50937
GSK Investigational Site
Demmin, Mecklenburg-Vorpommern, 17109
GSK Investigational Site
Hamburg, 22297
GSK Investigational Site
Heidelberg, Baden-Wurttemberg, 69120
GSK Investigational Site
Lehrte, Lower Saxony, 31275
GSK Investigational Site
Oberschleißheim, Bavaria, 85764
Canada5 sites
GSK Investigational Site
Calgary, Alberta, T2R 0X7
GSK Investigational Site
Edmonton, Alberta, T6G 2B7
GSK Investigational Site
Greater Sudbury, Ontario, P3E 5J1
GSK Investigational Site
Halifax, Nova Scotia, B3H 1V7
GSK Investigational Site
London, Ontario, N6A 5A5
Denmark3 sites
GSK Investigational Site
Aalborg, DK-9000
GSK Investigational Site
Odense, DK-5000
GSK Investigational Site
Roskilde, DK-4000
Sweden3 sites
GSK Investigational Site
Karlstad, SE-651 85
GSK Investigational Site
Stockholm, SE-141 86
GSK Investigational Site
Uppsala, SE-751 85
Norway2 sites
GSK Investigational Site
Oslo, 0027
GSK Investigational Site
Oslo, 0405
About this study
Official title: A Four-week, Phase IIa, Randomized, Active-controlled, Parallel-group, Multi-center Study to Evaluate the Safety, Efficacy and Pharmacokinetics of Switching Subjects From a Stable Dose of Recombinant Human Erythropoietin to GSK1278863 in Hemodialysis-dependent Subjects With Anemia Associated With Chronic Kidney Disease
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).
Read the 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.
- Conditions
- Anaemia
- Being tested
- GSK1278863, rhEPO
- Keywords
- Renal Impairment, Anemia, pharmacokinetics, hemodialysis, Chronic kidney disease, GSK1278863, hemoglobin, Prolyl hydroxylase inhibitor, recombinant human erythropoietin, erythropoiesis stimulating agents, Dialysis, Renal
- Medical subject headings
- Anemia, Renal Insufficiency, Renal Insufficiency, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GSK1278863Drug
tablet
rhEPODrug
injection
| Study group | Role | What they receive |
|---|---|---|
| 0.5 mg GSK1278863 | Experimental | once daily Receives: Drug: GSK1278863 |
| 2 mg GSK1278863 | Experimental | once daily Receives: Drug: GSK1278863 |
| 5 mg GSK1278863 | Experimental | once daily Receives: Drug: GSK1278863 |
| rhEPO | Active comparator | as required Receives: Drug: rhEPO |
What is being measured
The primary outcome is the main question the study is designed to answer.
Modeled Hemoglobin (Hgb) Change From Baseline (Pre-dose on Day 1) at 4 Weeks of Treatment
Modeled Hgb change from Baseline over 4 weeks of treatment. Change from Baseline is the actual value of Hgb at Week 4 minus the Baseline value. For modeled change at Week 4 participants required a Baseline and two or more non missing post-baseline values. Baseline is the average of Week -2, -1 and Day 1 values. The model included fixed effects for Baseline Hgb, treatment, and treatment by day interaction. Covariate analysis for modeled Hgb change was performed. Random effects were fitted in the intercept and the slope over time.
Measured: Baseline (pre-dose on Day 1) and up to week 4
Secondary outcomes (22)
Hgb Variability Over 4 Weeks
Within participant standard deviation for Hgb acts as a measure of Hgb variability. Hgb of participants was recorded over 4 weeks.
Measured: Up to 4 weeks
Evaluation of Change From Baseline in Hepcidin Over Period
Evaluation of change from baseline for hepcidin was performed over 4 weeks. Change from Baseline is the value at indicated time point minus the Baseline value. Baseline was the last pre-dose value. Adjusted mean change from Baseline is presented as Least square (LS) mean.
Measured: Baseline (pre-dose on Day 1) and up to 4 weeks
Evaluation of Change From Baseline (Pre-dose on Day 1) in High Sensitivity C-Reactive Protein (hsCRP) Over 4 Weeks
Evaluation of change from Baseline for hsCRP was analyzed over 4 weeks. Change from Baseline is the value at indicated time point minus the Baseline value. Baseline was the last pre-dose value. Peak change from Baseline also was calculated; however adjusted mean change from Baseline has been presented here as LS means.
Measured: Baseline (pre-dose on Day 1) and up to 4 weeks
Change From Baseline for Erythropoeitin (EPO) Over Period
Evaluation of change from Baseline (pre-dose on Day 1) for EPO was analyzed over 4 weeks. Change from Baseline is the value at indicated time point minus the Baseline value. Baseline was the pre-dose Day 1 value. Adjusted means are presented as LS means.
Measured: Baseline (pre-dose on Day 1) and up to 4 weeks
Evaluation of Change From Baseline (Pre-dose on Day 1) for Peak Vascular Endothelial Growth Factor (VEGF) Over 4 Weeks
Evaluation of change from Baseline for peak VEGF was analyzed up to 4 weeks. Baseline assessment was performed pre-dose on Day 1. Change from Baseline is the value at indicated time point minus the Baseline value. Absolute mean change and peak change from Baseline in peak VGEF were also calculated; however, only model adjusted peak change in peak VGEF from Baseline has been presented as LS means.
Measured: Baseline (pre-dose on Day 1) and up to 4 weeks
Evaluation of Change From Baseline (Pre-dose on Day 1) for Hematocrit Over 4 Weeks
Evaluation of change from Baseline for hematocrit over 4 weeks was performed. Change from Baseline is the value at indicated time point minus the Baseline value.
Measured: Baseline (pre-dose on Day 1) and up to 4 weeks
Residual Standard Deviation in Hgb (From the Linear Regression)
Residual standard deviation was derived by linear regression. Hgb of participants was recorded over 4 weeks
Measured: Up to 4 weeks
Number of Days Spent Within Hgb Range ( ±0.5 g/dL and ±1 g/dL ) From Baseline Hgb
Time spent with Hgb within range (where range was defined as +-0.5 g/dL and +-1 g/dL from baseline Hgb ) was analyzed. Baseline value of Hgb was recorded pre-dose on Day 1.
Measured: Baseline (pre-dose on Day 1) and up to 4 weeks
Evaluation of Change From Baseline (Pre-dose on Day 1) in Ferritin Over 4 Weeks
Change from Baseline (pre-dose on Day 1) in ferritin over 4 weeks was analyzed. Change from Baseline is the value at indicated time point minus the Baseline value. Model adjusted mean has been presented as LS mean.
Measured: Baseline (pre-dose on Day 1) and Week 4
Evaluation of Change From Baseline (Pre-dose on Day 1) for Transferrin Over 4 Weeks
Evaluation of change from Baseline for ferritin was performed over 4 weeks. Change from Baseline is the value at indicated time point minus the Baseline value. Model adjusted mean has been presented as LS mean.
Measured: Baseline (pre-dose on Day 1) and Week 4
Change From Baseline (Pre-dose on Day 1) for Transferrin Saturation Over 4 Weeks
Transferrin saturation is a medical laboratory test and is the ratio of serum iron and total iron-binding capacity, multiplied by 100 and expressed as a ratio. Evaluation of change from baseline for transferrin saturation was performed up to 4 weeks. Change from Baseline is the value at indicated time point minus the Baseline value. Baseline value was recorded pre-dose on Day 1. Model adjusted mean values are presented as LS mean values.
Measured: Baseline (pre-dose on Day 1) and Week 4
Change From Baseline (Pre-dose on Day 1) for Total Iron Over 4 Weeks
Evaluation of change from Baseline for total iron was performed over 4 weeks. Change from Baseline is the value at indicated time point minus the Baseline value. Baseline was recorded pre-dose on Day 1. Adjusted mean was presented as LS mean.
Measured: Baseline (pre-dose on Day 1) and at Week 4
Change From Baseline (Pre-dose on Day 1) in Total Iron Binding Capacity Over 4 Weeks
Evaluation of change from Baseline in total iron binding capacity was performed over 4 weeks. Baseline was recorded pre-dose on Day 1. Change from Baseline is the value at indicated time point minus the Baseline value. Adjusted means are presented as LS means.
Measured: Baseline (pre-dose on Day 1) and Week 4
Change From Baseline (Pre-dose on Day 1) for Red Blood Cells (RBCs) Over 4 Weeks
Change from Baseline in RBCs was a pharmacodynamic (PD) biomarker. Change from Baseline is the value at indicated time point minus the Baseline value. Baseline was recorded pre-dose on Day 1. Change from Baseline (pre-dose on Day 1) in RBCs was calculated over 4 weeks.
Measured: Baseline (pre-dose on Day 1) and up to 4 weeks
Change From Baseline (Pre-dose on Day 1) for Reticulocytes Over 4 Weeks
Evaluation of change from Baseline for reticulocytes was a PD parameter. Change from Baseline is the value at indicated time point minus the Baseline value. Baseline value was recorded pre-dose on Day 1.
Measured: Baseline (pre-dose on Day 1) and up to 4 weeks
Number of Participants Reaching Hgb Stopping Criteria
Participants were analyzed whether they had any increase or decrease from the Baseline Hgb. Hgb increase based stopping criteria included analysis of Increase or decrease of more than or equal to (>=) 2 g/dL from the Baseline (pre-dose on Day 1) was recorded and also the participants with hemoglobin >=13 g/dL were recorded.
Measured: Up to 4 weeks
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE is an unfavorable change in the health of a participant, including abnormal laboratory findings, that happens during a clinical study or within a certain time period after the study has ended. This change may or may not be caused by the intervention being studied. An SAE is an adverse event that results in death, is life-threatening, requires inpatient hospitalization or extends a current hospital stay, results in an ongoing or significant incapacity or interferes substantially with normal life functions, or causes a congenital anomaly or birth defect. Medical events that do not result in death, are not life-threatening, or do not require hospitalization may be considered serious adverse events if they put the participant in danger or require medical or surgical intervention to prevent one of the results listed above. Only on-treatment data has been presented.
Measured: Up to 4 weeks
Number of Participants Discontinuing the Study Treatment Due to AEs
Discontinuation of the study drug could be due to safety-related reasons AE. The AEs responsible included anemia, gastrointestinal hemorrhage, and nausea.
Measured: Up to 4 weeks
Mean Plasma Concentration of GSK1278863 and GSK1278863 Metabolites Over 4 Weeks
Each of the plasma concentration-time plot contained one plot on the untransformed scale (i.e. a linear plot) and one plot on the log transformed scale (i.e. log-linear plot). Plasma concentrations were analyzed for the study drug (GSK1278863), and its metabolites namely GSK2391220 (M2), GSK2531403 (M3), GSK2487818A (M4), GSK2506102A (M5), GSK2531398 (M6), and GSK2531401A (M13). Pharmacokinetic analysis was done on Weeks (W) 2 and 4 at a fixed timely interval of 5 hours (h) on W2 and every hour on W4. Only the data for last visit for W2 and last visit of W4 has been presented.
Measured: Up to 4 weeks
Number of Participants With Abnormal Hematology and Clinical Chemistry Parameters of Potential Clinical Concern (PCI)
Participants were analyzed up to 6 weeks for hematological and clinical chemistry parameters of PCI whether they had any higher or lower values than the reference range post screening. Normal alkaline phosphatase (ALP) was 0-46 U/L, aspartate amino transferase (AST) 0-42 U/L, ALP 20-125 U/L, total bilirubin 0-1.3 mg/dL, troponin 0-0.1ng/mL, Hgb 12 - 16 g/dL, platelets 140-450 G/L, creatine phosphokinase 29-168 U/L, creatinine 0.57 - 1.25 mg/dL, Potassium 3.6-5.0 mmol/L, hematocrit 38-45%; however, no participants with abnormal hematology and clinical chemistry parameters were recorded.
Measured: Up to 6 weeks (including follow-up)
Number of Participants With Abnormal Vital Signs of PCI
Vital signs include systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR). Three measurements of SBP, DBP and HR were recorded from the participant in a supine position for at least 5 minutes (allowing enough time between measurement to completely deflate and loosen the inflatable cuff). Data has been presented for vital signs with values high and low from the reference range.
Measured: Up to 6 weeks
Number of Participants With Electrocardiogram (ECG) Findings Over Period
Participants were analyzed for any abnormality in ECG and was categorized as abnormal clinically significant and abnormal and clinically insignificant. The parameters that were analyzed for ECG were atrial fibrillation, Atrial premature complex, Bigeminy, First degree AV block (PR interval > 200 msec), Incomplete right bundle branch block, Junctional rhythm, Junctional tachycardia (heart rate >100 beats/min), Left anterior hemi block (synonymous to left anterior fascicular block), Left atrial abnormality, Left axis deviation (QRS axis more negative than -30 degrees), Left bundle branch block, Left ventricular hypertrophy, Myocardial infarction, anterior, Myocardial infarction, inferior, Non-specific ST-T changes, Normal sinus rhythm, Poor R wave progression, Right atrial abnormality, Right QRS axis deviation, bundle block, ventricular hypertrophy, ST depression or abnormality, AV block, arrhythmia, short PR interval, bradycardia, tachycardia, and T-wave abnormality.
Measured: Up to 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Apr 2012 (estimated)
- Study start23 May 2012
- Primary completion27 May 2013
- Study completion27 May 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for AnaemiaStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 80 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- PPD Development, LP
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01587924
- Sponsor's protocol ID
- 116582
- Status last verified
- Aug 2017
- First submitted
- 23 Apr 2012
- Last updated
- 14 Nov 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Yes: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
Publications
Natale P, Palmer SC, Jaure A, Hodson EM, Ruospo M, Cooper TE, Hahn D, Saglimbene VM, Craig JC, Strippoli GF. Hypoxia-inducible factor stabilisers for the anaemia of chronic kidney disease. Cochrane Database Syst Rev. 2022 Aug 25;8(8):CD013751. doi: 10.1002/14651858.CD013751.pub2.
PubMed 36005278Holdstock L, Meadowcroft AM, Maier R, Johnson BM, Jones D, Rastogi A, Zeig S, Lepore JJ, Cobitz AR. Four-Week Studies of Oral Hypoxia-Inducible Factor-Prolyl Hydroxylase Inhibitor GSK1278863 for Treatment of Anemia. J Am Soc Nephrol. 2016 Apr;27(4):1234-44. doi: 10.1681/ASN.2014111139. Epub 2015 Oct 22.
PubMed 26494831
Study at a glance
From the registry record, last updated by the sponsor on 14 Nov 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Four-week, Phase IIa, Randomized, Active-controlled, Parallel-group, Multi-center Study to Evaluate the Safety, Efficacy and Pharmacokinetics of Switching Subjects From a Stable Dose of Recombinant Human Erythropoietin to GSK1278863 in Hemodialysis-dependent Subjects With Anemia Associated With Chronic Kidney Disease
- ClinicalTrials.gov ID
- NCT01587924
- Acronym / sponsor ID
- 116582
- Conditions
- Anaemia
- Keywords
- Renal Impairment, Anemia, pharmacokinetics, hemodialysis, Chronic kidney disease, GSK1278863, hemoglobin, Prolyl hydroxylase inhibitor
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 80 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Collaborators
- PPD Development, LP
- Study start
- 23 May 2012 (actual)
- Primary completion
- 27 May 2013 (actual)
- Study completion
- 27 May 2013 (actual)
- First posted
- 30 Apr 2012 (estimated)
- Results
- Posted 12 Sep 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 0.5 mg GSK1278863 | Experimental | Drug: GSK1278863once daily |
| 2 mg GSK1278863 | Experimental | Drug: GSK1278863once daily |
| 5 mg GSK1278863 | Experimental | Drug: GSK1278863once daily |
| rhEPO | Active comparator | Drug: rhEPOas required |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Age and weight: >/=18 years of age and >/=45 kg (weight post-dialysis).
- On three times weekly hemodialysis for at least 8 weeks, irrespective of eGFR values and stage of chronic kidney disease (CKD).
- A single-pool Kt/Vurea of >/=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%.
- rhEPO use: Using the same rhEPO (epoetins or darbepoetin) with total weekly doses that varied by no more than 50% during the prior 4 weeks (i.e., maximum vs. minimum total weekly doses </=50%).
- Hgb concentrations 9.5-12.0 g/dL (inclusive).
Key exclusion criteria (30 listed)
- Dialysis modality: On peritoneal dialysis OR planned change in dialysis modality within the study time period.
- rhEPO Hyporesponders: As defined by an epoetin dose of >/=360 IU/kg/week IV or darbepoetin dose of >/=1.8 µg/kg/week IV within the prior 8 weeks.
- Renal transplant: Renal transplant anticipated or scheduled within the study time period or subjects with a functioning renal transplant.
- Mircera or Peginesatide: Current or prior use (within the prior 8 weeks) of Mircera (methoxy polyethylene glycol epoetin beta) OR peginesatide.
- Total CPK: >5x the upper limit of the reference range.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GSK1278863tablet | Drug | 0.5 mg GSK1278863, 2 mg GSK1278863, 5 mg GSK1278863 |
| rhEPOinjection | Drug | rhEPO |
Primary outcome
Modeled Hemoglobin (Hgb) Change From Baseline (Pre-dose on Day 1) at 4 Weeks of Treatment
Time frame: Baseline (pre-dose on Day 1) and up to week 4
Modeled Hgb change from Baseline over 4 weeks of treatment. Change from Baseline is the actual value of Hgb at Week 4 minus the Baseline value. For modeled change at Week 4 participants required a Baseline and two or more non missing post-baseline values. Baseline is the average of Week -2, -1 and Day 1 values. The model included fixed effects for Baseline Hgb, treatment, and treatment by day interaction. Covariate analysis for modeled Hgb change was performed. Random effects were fitted in the intercept and the slope over time.
22 secondary outcomes
Hgb Variability Over 4 Weeks
Time frame: Up to 4 weeks
Evaluation of Change From Baseline in Hepcidin Over Period
Time frame: Baseline (pre-dose on Day 1) and up to 4 weeks
Evaluation of Change From Baseline (Pre-dose on Day 1) in High Sensitivity C-Reactive Protein (hsCRP) Over 4 Weeks
Time frame: Baseline (pre-dose on Day 1) and up to 4 weeks
Change From Baseline for Erythropoeitin (EPO) Over Period
Time frame: Baseline (pre-dose on Day 1) and up to 4 weeks
Evaluation of Change From Baseline (Pre-dose on Day 1) for Peak Vascular Endothelial Growth Factor (VEGF) Over 4 Weeks
Time frame: Baseline (pre-dose on Day 1) and up to 4 weeks
Evaluation of Change From Baseline (Pre-dose on Day 1) for Hematocrit Over 4 Weeks
Time frame: Baseline (pre-dose on Day 1) and up to 4 weeks
Residual Standard Deviation in Hgb (From the Linear Regression)
Time frame: Up to 4 weeks
Number of Days Spent Within Hgb Range ( ±0.5 g/dL and ±1 g/dL ) From Baseline Hgb
Time frame: Baseline (pre-dose on Day 1) and up to 4 weeks
Evaluation of Change From Baseline (Pre-dose on Day 1) in Ferritin Over 4 Weeks
Time frame: Baseline (pre-dose on Day 1) and Week 4
Evaluation of Change From Baseline (Pre-dose on Day 1) for Transferrin Over 4 Weeks
Time frame: Baseline (pre-dose on Day 1) and Week 4
Change From Baseline (Pre-dose on Day 1) for Transferrin Saturation Over 4 Weeks
Time frame: Baseline (pre-dose on Day 1) and Week 4
Change From Baseline (Pre-dose on Day 1) for Total Iron Over 4 Weeks
Time frame: Baseline (pre-dose on Day 1) and at Week 4
Change From Baseline (Pre-dose on Day 1) in Total Iron Binding Capacity Over 4 Weeks
Time frame: Baseline (pre-dose on Day 1) and Week 4
Change From Baseline (Pre-dose on Day 1) for Red Blood Cells (RBCs) Over 4 Weeks
Time frame: Baseline (pre-dose on Day 1) and up to 4 weeks
Change From Baseline (Pre-dose on Day 1) for Reticulocytes Over 4 Weeks
Time frame: Baseline (pre-dose on Day 1) and up to 4 weeks
Number of Participants Reaching Hgb Stopping Criteria
Time frame: Up to 4 weeks
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: Up to 4 weeks
Number of Participants Discontinuing the Study Treatment Due to AEs
Time frame: Up to 4 weeks
Mean Plasma Concentration of GSK1278863 and GSK1278863 Metabolites Over 4 Weeks
Time frame: Up to 4 weeks
Number of Participants With Abnormal Hematology and Clinical Chemistry Parameters of Potential Clinical Concern (PCI)
Time frame: Up to 6 weeks (including follow-up)
Number of Participants With Abnormal Vital Signs of PCI
Time frame: Up to 6 weeks
Number of Participants With Electrocardiogram (ECG) Findings Over Period
Time frame: Up to 6 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Nov 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36005278Natale P, Palmer SC, Jaure A, Hodson EM, Ruospo M, Cooper TE, Hahn D, Saglimbene VM, Craig JC, Strippoli GF. Hypoxia-inducible factor stabilisers for the anaemia of chronic kidney disease. Cochrane Database Syst Rev. 2022 Aug 25;8(8):CD013751. doi: 10.1002/14651858.CD013751.pub2.
- Derived from this study: PubMed 26494831Holdstock L, Meadowcroft AM, Maier R, Johnson BM, Jones D, Rastogi A, Zeig S, Lepore JJ, Cobitz AR. Four-Week Studies of Oral Hypoxia-Inducible Factor-Prolyl Hydroxylase Inhibitor GSK1278863 for Treatment of Anemia. J Am Soc Nephrol. 2016 Apr;27(4):1234-44. doi: 10.1681/ASN.2014111139. Epub 2015 Oct 22.
- Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
62 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing GSK1278863 and rhEPO in people with Anaemia, run by GlaxoSmithKline at 62 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Nov 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 62 sites in United States, Germany, Canada, Denmark, Sweden and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Sep 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Modeled Hemoglobin (Hgb) Change From Baseline (Pre-dose on Day 1) at 4 Weeks of Treatment (time frame: Baseline (pre-dose on Day 1) and up to week 4). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01587924, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Nov 2017.