AnaemiaPhase 2NCT01977482
Evaluation of Dose Response Relationship, Safety and Efficacy of GSK1278863 in Hemodialysis-dependent Subjects With Chronic Kidney Disease Associated Anemia
A Phase 2 study testing GSK1278863 and rhEPO in people with Anaemia, run by GlaxoSmithKline at 107 sites in 16 countries.
Trial summary
This study is intended to evaluate the dose-response relationship of GSK1278863 over the first 4 weeks of treatment and evaluate the safety and efficacy of GSK1278863 over 24 weeks to maintain hemoglobin (Hgb) level in hemodialysis-dependent (HDD) subjects with anemia associated with chronic kidney disease (CKD) who… 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
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 216 participants
- Where
- 107 sitesin 16 countries
- Study dates
- 1 Nov 2013to 6 Feb 2015
- 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
- - Subjects are eligible if they meet all of the inclusion criteria below:
- General 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 [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) 23.0-116.3 International units per liter (IU/L) and estradiol <=10 picomole per liter (pmol/L) 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 must 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;
- Q-T Interval Corrected for Heart Rate (QTc): Bazett's Correction of QT Interval (QTcB) <470 millisecond (msec) or QTcB <480 msec in subjects with bundle branch block. There is no QTc inclusion criterion for a subject with a predominantly paced rhythm.
- CKD-related criteria
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- Dialysis frequency: On hemodialysis (HD) three to five times weekly for at least 4 weeks prior to Week -4 Screening through Week 4. NOTE: Combination methods including hemofiltration (HF) or ultrafiltration (UF) with HD are allowed. However, the type of dialysis (HD, hemodiafiltration (HDF) or UF) should not change during the study.
- Dialysis adequacy: A single-pool dialyzer clearance multiplied by dialyzer time divided by volume of distribution of urea (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%. NOTE: Only needs confirming at Week -4.
- Hemoglobin: Baseline Hgb of 9.0-11.5 g/dL (may rescreen in a minimum of 2 weeks).
- 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 doses varied by no more than 50% during the screening period.
- Iron replacement therapy: Subjects may be on stable maintenance oral or IV (<=100 mg/week) iron supplementation. If subjects are on oral or IV iron, then doses must be stable for the 4 weeks prior to Week -4, during the screening phase, and through the first 4 weeks after Randomization.
Who cannot join
- Subjects are not eligible if they meet any of the exclusion criteria below:
- CKD-related criteria
- Dialysis modality: Planned change from HD to peritoneal dialysis within the study time period.
- Renal transplant: Pre-emptive or scheduled renal transplant.
- High rhEPO dose: An epoetin dose of >=360 IU/Kg/Week IV or >=250 IU/kg/week subcutaneous (SC) or darbepoetin dose of >=1.8 microgram (µg)/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).
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- Laboratory test-based criteria (Week -4 verification only)
- Vitamin B12: At or below the lower limit of the reference range (may rescreen in a minimum of 8 weeks).
- Folate: <2.0 nanogram (ng)/mL (<4.5 nanomole (nmol)/L) (may rescreen in a minimum of 4 weeks).
- Ferritin: <100 ng/mL (<100 Micrograms per liter).
- Transferrin saturation (TSAT): Outside of the reference range.
- Cardiovascular disease-related criteria
- 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).
- Hypertension: Defined using pre-dialysis vitals (Week -4, Day 1) of diastolic blood pressure (DBP) >100 millimeters of mercury (mmHg) or systolic blood pressure (SBP) >170 mmHg.
- 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).
- Other disease-related criteria
- 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. NOTE: Those with Hepatitis B or Hepatitis C are eligible provided these exclusions are not met.
- 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.
- 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 intravenous (IV) antibiotic therapy within the 8 weeks prior to Week -4 Screening through Day 1 (randomization). NOTE: IV antibiotics as prophylaxis are allowed.
- 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).
- Concomitant medication and other Investigational Product-related criteria
- Severe allergic 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 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).
- General health-related criteria
- Other Conditions: Any other condition, clinical or laboratory abnormality, or examination finding that the Investigator considers would put the subject at unacceptable risk.
- Pregnancy or Lactation: Pregnant females as determined by positive serum human chorionic gonadotropin (hCG) test OR women who are lactating at Week -4 Screening or during the trial.
- Other Eligibility Criteria Considerations
- Laboratory eligibility criteria will be assessed according to the central laboratory results for the screening samples.
- Subjects who fail screening may be rescreened as soon as the investigator feels they may have become eligible. However, an individual subject may not rescreen more than twice. There is no predetermined amount of time that the investigator needs to wait to rescreen a previously ineligible subject, except those excluded for Hgb or folate who may only rescreen in 2 and 4 weeks, respectively, and those excluded for Vitamin B12 who may rescreen in 8 weeks
Trial locations and contacts
107 sites in 16 countries.
107 sites in 16 countries
United States17 sites
GSK Investigational Site
Amherst, New York, 14226
GSK Investigational Site
Azusa, California, 91702
GSK Investigational Site
Bethesda, Maryland, 20814
GSK Investigational Site
Charlotte, North Carolina
GSK Investigational Site
Evergreen Park, Illinois, 60805
GSK Investigational Site
Farmington, Missouri, 63640
GSK Investigational Site
Knoxville, Tennessee, 37923
GSK Investigational Site
Lauderdale Lakes, Florida, 33313
GSK Investigational Site
Los Angeles, California, 90022
GSK Investigational Site
Los Angeles, California, 90025
GSK Investigational Site
Macon, Georgia, 31217
GSK Investigational Site
Pembroke Pines, Florida, 33028
GSK Investigational Site
San Antonio, Texas, 78229
GSK Investigational Site
San Dimas, California, 91773
GSK Investigational Site
Temple, Texas, 76502
GSK Investigational Site
The Bronx, New York, 10461
GSK Investigational Site
West Hills, California, 91307
Spain12 sites
GSK Investigational Site
Alcalá de Henares, 28805
GSK Investigational Site
Alicante, 03010
GSK Investigational Site
Almería, 04009
GSK Investigational Site
Badalona, 08916
GSK Investigational Site
Barcelona, 08907
GSK Investigational Site
Córdoba, 14004
GSK Investigational Site
Granada, 18014
GSK Investigational Site
Madrid, 28007
GSK Investigational Site
Madrid, 28224
GSK Investigational Site
San Sebastián de los Reyes, 28702
GSK Investigational Site
Santander, 39008
GSK Investigational Site
Santiago de Compostela, 15706
Russia9 sites
GSK Investigational Site
Kaluga, 248007
GSK Investigational Site
Krasnodar, 350029
GSK Investigational Site
Krasnogorsk, 143400
GSK Investigational Site
Moscow, 125101
GSK Investigational Site
Mytischi, 141009
GSK Investigational Site
Novosibirsk, 630087
GSK Investigational Site
Saint Petersburg, 191104
GSK Investigational Site
Saint Petersburg, 194354
GSK Investigational Site
Yaroslavl, 150062
Japan8 sites
GSK Investigational Site
Aichi, 441-8023
GSK Investigational Site
Ehime, 790-0952
GSK Investigational Site
Ehime, 790-0962
GSK Investigational Site
Fukuoka, 803-0844
GSK Investigational Site
Kyoto, 617-0813
GSK Investigational Site
Niigata, 940-0053
GSK Investigational Site
Wakayama, 640-8335
GSK Investigational Site
Yamagata, 990-0834
Czechia7 sites
GSK Investigational Site
Liberec, 460 63
GSK Investigational Site
Louny, 440 01
GSK Investigational Site
Most, 434 64
GSK Investigational Site
Prague, 100 34
GSK Investigational Site
Prague, 128 08
GSK Investigational Site
Prague, 142 00
GSK Investigational Site
Sokolov, 356 01
Germany7 sites
GSK Investigational Site
Berlin, 12053
GSK Investigational Site
Demmin, Mecklenburg-Vorpommern, 17109
GSK Investigational Site
Düsseldorf, North Rhine-Westphalia, 40210
GSK Investigational Site
Hamburg, 22297
GSK Investigational Site
Leipzig, Saxony, 04129
GSK Investigational Site
Mannheim, Baden-Wurttemberg, 68167
GSK Investigational Site
Munich, Bavaria, 81675
United Kingdom7 sites
GSK Investigational Site
Chelmsford, CM1 7ET
GSK Investigational Site
Dorchester, DT1 2JY
GSK Investigational Site
Dundee, DD1 9SY
GSK Investigational Site
Hull, HU3 2JZ
GSK Investigational Site
London, E1 1BB
GSK Investigational Site
Manchester, M13 9WL
GSK Investigational Site
Oxford, OX3 7LE
Canada6 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
Kitchener, Ontario, N2G 1G3
GSK Investigational Site
London, Ontario, N6A 5A5
GSK Investigational Site
Montreal, Quebec, H1T 2M4
South Korea6 sites
GSK Investigational Site
Anyang-Si Gyeonggi-do, 431-070
GSK Investigational Site
Daegu, 700-721
GSK Investigational Site
Daejeon, 301-721
GSK Investigational Site
Gwangju, 501-757
GSK Investigational Site
Incheon, 405-760
GSK Investigational Site
Seoul, 120-752
Australia5 sites
GSK Investigational Site
Adelaide, South Australia, 5000
GSK Investigational Site
Liverpool, New South Wales, 2170
GSK Investigational Site
Nedlands, Western Australia, 6009
GSK Investigational Site
Westmead, New South Wales, 2145
GSK Investigational Site
Woolloongabba, Queensland, 4102
Norway5 sites
GSK Investigational Site
Oslo, 0027
GSK Investigational Site
Oslo, 0405
GSK Investigational Site
Stavanger, 4011
GSK Investigational Site
Tønsberg, 3116
GSK Investigational Site
Trondheim, 7006
France4 sites
GSK Investigational Site
Amiens, 80054
GSK Investigational Site
Bordeaux, 33000
GSK Investigational Site
Caen, 14033
GSK Investigational Site
Paris, 75743
Hungary4 sites
GSK Investigational Site
Budapest, 1115
GSK Investigational Site
Esztergom, 2500
GSK Investigational Site
Pécs, 7624
GSK Investigational Site
Pécs, 7633
Poland4 sites
GSK Investigational Site
Krakow, 31-501
GSK Investigational Site
Tarnów, 33-100
GSK Investigational Site
Warsaw, 02-507
GSK Investigational Site
Zabrze, 41-800
Sweden4 sites
GSK Investigational Site
Karlstad, SE-651 85
GSK Investigational Site
Örebro, SE-701 85
GSK Investigational Site
Stockholm, SE-141 86
GSK Investigational Site
Uppsala, SE-751 85
Denmark2 sites
GSK Investigational Site
Odense C, 5000
GSK Investigational Site
Roskilde, DK-4000
About this study
Official title: A Phase IIB, Randomized, Blinded, Dose-ranging, Active-controlled, Parallel-group, Multi-center Study to Evaluate the Dose Response Relationship of GSK1278863 Over the First 4 Weeks of Treatment and Evaluate the Safety and Efficacy of GSK1278863 Over 24 Weeks in Hemodialysis-Dependent Subjects With Anemia Associated With Chronic Kidney Disease Who Switch From Recombinant Human Erythropoietin
This study is intended to evaluate the dose-response relationship of GSK1278863 over the first 4 weeks of treatment and evaluate the safety and efficacy of GSK1278863 over 24 weeks to maintain hemoglobin (Hgb) level in hemodialysis-dependent (HDD) subjects with anemia associated with chronic kidney disease (CKD) who are switched from a stable dose of recombinant human erythropoietin (rhEPO). The data generated will enable selection of the starting dose(s) and optimize dose adjustment regimen(s) for Phase 3 clinical trials.
- Conditions
- Anaemia
- Being tested
- GSK1278863, Placebo, rhEPO
- Keywords
- hemoglobin, recombinant human erythropoietin, Chronic kidney disease, hemodialysis, pharmacokinetics, erythropoiesis stimulating agents, Anemia, GSK1278863
- Medical subject headings
- Anemia, Renal Insufficiency, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GSK1278863Drug
Film coated tablets containing 1 mg, 2 mg, 5 mg, or 25 mg of GSK1278863
PlaceboDrug
Matching placebo tablet for GSK1278863
rhEPODrug
rhEPO will be procured from local market
| Study group | Role | What they receive |
|---|---|---|
| GSK1278863 4 mg | Experimental | Subjects will take GSK1278863 4 mg blinded once daily (OD) orally for 4 weeks with a glass of water. From Week 4, study medication will continue to be administered OD and the dose will be adjusted based on Hgb levels dose every 4 weeks till Week 24. Receives: Drug: GSK1278863 |
| GSK1278863 6 mg | Experimental | Subjects will take GSK1278863 6 mg blinded OD orally for 4 weeks with a glass of water. From Week 4, study medication will continue to be administered OD and the dose will be adjusted based on Hgb levels dose every 4 weeks till Week 24. Receives: Drug: GSK1278863 |
| GSK1278863 8 mg | Experimental | Subjects will take GSK1278863 8 mg blinded OD orally for 4 weeks with a glass of water. From Week 4, study medication will continue to be administered OD and the dose will be adjusted based on Hgb levels dose every 4 weeks till Week 24. Receives: Drug: GSK1278863 |
| GSK1278863 10 mg | Experimental | Subjects will take GSK1278863 10 mg blinded OD orally for 4 weeks with a glass of water. From Week 4, study medication will continue to be administered OD and the dose will be adjusted based on Hgb levels dose every 4 weeks till Week 24. Receives: Drug: GSK1278863 |
| GSK1278863 12 mg | Experimental | Subjects will take GSK1278863 12 mg blinded OD orally for 4 weeks with a glass of water. From Week 4, study medication will continue to be administered OD and the dose will be adjusted based on Hgb levels dose every 4 weeks till Week 24. Receives: Drug: GSK1278863 |
| Control | Active comparator | Subjects will take GSK1278863 matching placebo blinded OD orally for 4 weeks with a glass of water. From Week 4, rhEPO will be administered and the dose will be adjusted based on Hgb levels dose every 4 weeks till Week 24. Receives: Drug: Placebo; Drug: rhEPO |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in Hemoglobin (Hgb) at Week 4
Baseline Hgb value was the average of three Hgb values taken during screening period at Week (W) -4, W-2 and Day 1. Change from Baseline in Hgb was calculated as W4 value minus the Baseline value. To model the dose-response relationship a four-parameter Emax model was used. The dose response dataset was based on all non-missing data collected up to W4. Participants (par.) who had a Week 2 Hgb measurement, but a missing Week 4 Hgb measurement were included with a change from Baseline at Week 4 value imputed as twice the change from Baseline at Week 2. E0 is the expected Hgb change from Baseline for a par. receiving placebo and experiencing the average Hgb Baseline observed in the study. Emax is the expected Hgb change from Baseline for a par. receiving the highest dose above which no further increase in response can be achieved. ED50 is the dose that attains the intermediate response. Gamma is the slope parameter. Alpha is the coefficient of the model covariate for centred Baseline.
Measured: Baseline (Week -4, Week-2 and Day 1) and Week 4
Secondary outcomes (17)
Hgb Concentration at Week 24
Hgb values measured at Week 24 are presented.
Measured: Week 24
Percentage of Time Within, Below, and Above Hgb Target Range Between Weeks 20 and 24
The percentage of time in Hgb target range between Weeks 20 and 24 for a participant was calculated by dividing the total number of days that Hgb was within the target range (10.0 to 11.5 g/dL) while on treatment during Weeks 20 to 24 (using linear interpolation) by the total number of days the participant remained on treatment during the defined period. Similarly, percentage of time above Hgb target range and percentage of time below Hgb target range were calculated.
Measured: Week 20 to Week 24
Number of Participants With Hgb in the Target Range at Week 24
The number of participants with Hgb in the target range of 10.0 to 11.5 g/dL at Week 24 was recorded for each arm.
Measured: Week 24
Number of Participants Reaching Pre-defined Hgb Stopping Criteria
The number of participants who reached the Hgb stopping criteria of Hgb concentration <7.5 g/dL were presented.
Measured: Up to 24 weeks
Maximum Observed Change From Baseline in Erythropoietin (EPO)
Blood samples for control arm were collected on Day 1 (pre-dose), Week 4 (5-15 minutes post-dose), Week 8 (pre-dose), Week 12 (pre-dose), Week 16 (pre-dose), Week 20 (pre-dose, 5-15 minutes post-dose), Week 24 (pre-dose), and Week 28 (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-dose values minus the Baseline value.
Measured: Baseline (Day 1) to Week 28
Maximum Observed Percent Change From Baseline in Vascular Endothelial Growth Factor (VEGF)
Blood samples for control arm were collected on Day 1 (pre-dose), Week 4 (5-15 minutes post-dose), Week 8 (pre-dose), Week 12 (pre-dose), Week 16 (pre-dose), Week 20 (pre-dose, 5-15 minutes post-dose), Week 24 (pre-dose), and Week 28 (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 percent change from Baseline in VEGF was recorded for each arm. Baseline value for VEGF is the pre-dose value on Day 1. Percent change from Baseline was calculated as 100 multiplied by exponential of mean change in log scale minus 1.
Measured: Baseline (Day 1) to Week 28
Population Plasma PK Parameters of GSK1278863 and Metabolites
Blood samples were collected for individual plasma GSK1278863and metabolite (GSK2391220, GSK2499166, GSK2531403, GSK2531400, GSK2531399, and GSK2531398) concentrations measurement on Day (D) 1 (pre-dose [PrD), at Week (W) 4 (6-12, 7-13, 8-14, and 9-15 hour [hr] post-dose [PoD), and at W20 (PrD, 1, 2, and 3 hour PoD). Pharmacokinetic population: All participants from whom a PK sample has been obtained and analyzed.
Measured: Day 1, Week 4, and Week 20
Percent Change From Baseline in Hepcidin at Week 24
Hepcidin is a regulator of iron metabolism. Baseline value for transferrin saturation is the pre-dose value on Day 1. Percent change from Baseline was calculated as 100 multiplied by exponential of mean change in log scale minus 1.
Measured: Baseline (Day 1) and Week 24
Change From Baseline in Ferritin at Week 24
Baseline value for ferritin is the pre-dose value on Day 1. Change from Baseline in ferritin was calculated as the Week 24 value minus the Baseline value.
Measured: Baseline (Day 1) and Week 24
Change From Baseline in Transferrin at Week 24
Baseline value for transferrin is the pre-dose value on Day 1. Change from Baseline in transferrin was calculated as the Week 24 value minus the Baseline value.
Measured: Baseline (Day 1) and Week 24
Percent Change From Baseline in Transferrin Saturation at Week 24
Transferrin saturation is measured as a percentage, it is the ratio of serum iron and total iron-binding capacity, multiplied by 100. Baseline value for transferrin saturation is the pre-dose value on Day 1. Percent change from Baseline =: 100*(exp(Mean change log scale)-1).
Measured: Baseline (Day 1) and Week 24
Change From Baseline in Total Iron at Week 24
Baseline value for total iron is the pre-dose value on Day 1. Change from Baseline in total iron was calculated as the Week 24 value minus the Baseline value.
Measured: Baseline (Day 1) and Week 24
Change From Baseline in Total Iron Binding Capacity at Week 24
Total iron-binding capacity is a medical laboratory test that measures the blood's capacity to bind iron with transferrin. Baseline value for total iron binding capacity is the pre-dose value on Day 1. Change from Baseline in total iron binding capacity was calculated as the Week 24 value minus the Baseline value.
Measured: Baseline (Day 1) and Week 24
Change From Baseline in Reticulocyte Hemoglobin at Week 24
Baseline value for reticulocyte hemoglobin is the pre-dose value on Day 1. Change from Baseline in reticulocyte hemoglobin was calculated as the Week 24 value minus the Baseline value.
Measured: Baseline (Day 1) and Week 24
Change From Baseline in Hematocrit at Week 24
Hematocrit is the ratio of the volume of red blood cells to the total volume of blood. Baseline value for hematocrit is the pre-dose value on Day 1. Change from Baseline in hematocrit was calculated as the Week 24 value minus the Baseline value.
Measured: Baseline (Day 1) and Week 24
Change From Baseline in Red Blood Cells at Week 24
Baseline value for red blood cells is the pre-dose value on Day 1. Change from Baseline in red blood cells was calculated as the Week 24 value minus the Baseline value.
Measured: Baseline (Day 1) and Week 24
Change From Baseline in Reticulocyte Count at Week 24
A reticulocyte count is a blood test that measures the percentage of reticulocytes in the blood. Reticulocytes are slightly immature red blood cells. Baseline value for reticulocyte count is the pre-dose value on Day 1. Change from Baseline in reticulocyte count was calculated as the Week 24 value minus the Baseline value.
Measured: Baseline (Day 1) and Week 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Nov 2013 (estimated)
- Study start1 Nov 2013
- Primary completion1 Feb 2015
- Study completion6 Feb 2015
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 (1)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
- 216 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01977482
- Sponsor's protocol ID
- 113633
- Status last verified
- May 2018
- First submitted
- 24 Oct 2013
- Last updated
- 8 Jun 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
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 36005278
Study at a glance
From the registry record, last updated by the sponsor on 8 Jun 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase IIB, Randomized, Blinded, Dose-ranging, Active-controlled, Parallel-group, Multi-center Study to Evaluate the Dose Response Relationship of GSK1278863 Over the First 4 Weeks of Treatment and Evaluate the Safety and Efficacy of GSK1278863 Over 24 Weeks in Hemodialysis-Dependent Subjects With Anemia Associated With Chronic Kidney Disease Who Switch From Recombinant Human Erythropoietin
- ClinicalTrials.gov ID
- NCT01977482
- Acronym / sponsor ID
- 113633
- Conditions
- Anaemia
- Keywords
- hemoglobin, recombinant human erythropoietin, Chronic kidney disease, hemodialysis, pharmacokinetics, erythropoiesis stimulating agents, Anemia, GSK1278863
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 216 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 1 Nov 2013
- Primary completion
- 1 Feb 2015 (actual)
- Study completion
- 6 Feb 2015 (actual)
- First posted
- 6 Nov 2013 (estimated)
- Results
- Posted 14 Feb 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is intended to evaluate the dose-response relationship of GSK1278863 over the first 4 weeks of treatment and evaluate the safety and efficacy of GSK1278863 over 24 weeks to maintain hemoglobin (Hgb) level in hemodialysis-dependent (HDD) subjects with anemia associated with chronic kidney disease (CKD) who are switched from a stable dose of recombinant human erythropoietin (rhEPO). The data generated will enable selection of the starting dose(s) and optimize dose adjustment regimen(s) for Phase 3 clinical trials.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| GSK1278863 4 mg | Experimental | Drug: GSK1278863Subjects will take GSK1278863 4 mg blinded once daily (OD) orally for 4 weeks with a glass of water. From Week 4, study medication will continue to be administered OD and the dose will be adjusted based on Hgb levels dose every 4 weeks till Week 24. |
| GSK1278863 6 mg | Experimental | Drug: GSK1278863Subjects will take GSK1278863 6 mg blinded OD orally for 4 weeks with a glass of water. From Week 4, study medication will continue to be administered OD and the dose will be adjusted based on Hgb levels dose every 4 weeks till Week 24. |
| GSK1278863 8 mg | Experimental | Drug: GSK1278863Subjects will take GSK1278863 8 mg blinded OD orally for 4 weeks with a glass of water. From Week 4, study medication will continue to be administered OD and the dose will be adjusted based on Hgb levels dose every 4 weeks till Week 24. |
| GSK1278863 10 mg | Experimental | Drug: GSK1278863Subjects will take GSK1278863 10 mg blinded OD orally for 4 weeks with a glass of water. From Week 4, study medication will continue to be administered OD and the dose will be adjusted based on Hgb levels dose every 4 weeks till Week 24. |
| GSK1278863 12 mg | Experimental | Drug: GSK1278863Subjects will take GSK1278863 12 mg blinded OD orally for 4 weeks with a glass of water. From Week 4, study medication will continue to be administered OD and the dose will be adjusted based on Hgb levels dose every 4 weeks till Week 24. |
| Control | Active comparator | Drug: Placebo, Drug: rhEPOSubjects will take GSK1278863 matching placebo blinded OD orally for 4 weeks with a glass of water. From Week 4, rhEPO will be administered and the dose will be adjusted based on Hgb levels dose every 4 weeks till Week 24. |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- - Subjects are eligible if they meet all of the inclusion criteria below:
- General 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 [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) 23.0-116.3 International units per liter (IU/L) and estradiol <=10 picomole per liter (pmol/L) 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 must 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;
- Q-T Interval Corrected for Heart Rate (QTc): Bazett's Correction of QT Interval (QTcB) <470 millisecond (msec) or QTcB <480 msec in subjects with bundle branch block. There is no QTc inclusion criterion for a subject with a predominantly paced rhythm.
Key exclusion criteria (37 listed)
- Subjects are not eligible if they meet any of the exclusion criteria below:
- CKD-related criteria
- Dialysis modality: Planned change from HD to peritoneal dialysis within the study time period.
- Renal transplant: Pre-emptive or scheduled renal transplant.
- High rhEPO dose: An epoetin dose of >=360 IU/Kg/Week IV or >=250 IU/kg/week subcutaneous (SC) or darbepoetin dose of >=1.8 microgram (µg)/Kg/Week IV or SC within the prior 8 weeks through Day 1 (randomization).
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 |
|---|---|---|
| GSK1278863Film coated tablets containing 1 mg, 2 mg, 5 mg, or 25 mg of GSK1278863 | Drug | GSK1278863 10 mg, GSK1278863 12 mg, GSK1278863 4 mg, GSK1278863 6 mg, GSK1278863 8 mg |
| PlaceboMatching placebo tablet for GSK1278863 | Drug | Control |
| rhEPOrhEPO will be procured from local market | Drug | Control |
Primary outcome
Change From Baseline in Hemoglobin (Hgb) at Week 4
Time frame: Baseline (Week -4, Week-2 and Day 1) and Week 4
Baseline Hgb value was the average of three Hgb values taken during screening period at Week (W) -4, W-2 and Day 1. Change from Baseline in Hgb was calculated as W4 value minus the Baseline value. To model the dose-response relationship a four-parameter Emax model was used. The dose response dataset was based on all non-missing data collected up to W4. Participants (par.) who had a Week 2 Hgb measurement, but a missing Week 4 Hgb measurement were included with a change from Baseline at Week 4 value imputed as twice the change from Baseline at Week 2. E0 is the expected Hgb change from Baseline for a par. receiving placebo and experiencing the average Hgb Baseline observed in the study. Emax is the expected Hgb change from Baseline for a par. receiving the highest dose above which no further increase in response can be achieved. ED50 is the dose that attains the intermediate response. Gamma is the slope parameter. Alpha is the coefficient of the model covariate for centred Baseline.
17 secondary outcomes
Hgb Concentration at Week 24
Time frame: Week 24
Percentage of Time Within, Below, and Above Hgb Target Range Between Weeks 20 and 24
Time frame: Week 20 to Week 24
Number of Participants With Hgb in the Target Range at Week 24
Time frame: Week 24
Number of Participants Reaching Pre-defined Hgb Stopping Criteria
Time frame: Up to 24 weeks
Maximum Observed Change From Baseline in Erythropoietin (EPO)
Time frame: Baseline (Day 1) to Week 28
Maximum Observed Percent Change From Baseline in Vascular Endothelial Growth Factor (VEGF)
Time frame: Baseline (Day 1) to Week 28
Population Plasma PK Parameters of GSK1278863 and Metabolites
Time frame: Day 1, Week 4, and Week 20
Percent Change From Baseline in Hepcidin at Week 24
Time frame: Baseline (Day 1) and Week 24
Change From Baseline in Ferritin at Week 24
Time frame: Baseline (Day 1) and Week 24
Change From Baseline in Transferrin at Week 24
Time frame: Baseline (Day 1) and Week 24
Percent Change From Baseline in Transferrin Saturation at Week 24
Time frame: Baseline (Day 1) and Week 24
Change From Baseline in Total Iron at Week 24
Time frame: Baseline (Day 1) and Week 24
Change From Baseline in Total Iron Binding Capacity at Week 24
Time frame: Baseline (Day 1) and Week 24
Change From Baseline in Reticulocyte Hemoglobin at Week 24
Time frame: Baseline (Day 1) and Week 24
Change From Baseline in Hematocrit at Week 24
Time frame: Baseline (Day 1) and Week 24
Change From Baseline in Red Blood Cells at Week 24
Time frame: Baseline (Day 1) and Week 24
Change From Baseline in Reticulocyte Count at Week 24
Time frame: Baseline (Day 1) and Week 24
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jun 2018.
- 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.
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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
107 sites in 16 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 107 sites in 16 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 11 inclusion and 37 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 8 Jun 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 107 sites in United States, Spain, Russia, Japan, Czechia and 11 more countries. 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 14 Feb 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?
Change From Baseline in Hemoglobin (Hgb) at Week 4 (time frame: Baseline (Week -4, Week-2 and Day 1) and 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 NCT01977482, which also lists 1 linked publication.
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 8 Jun 2018.