Trial document





This study has been imported from ClinicalTrials.gov without additional data checks.
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  DRKS00006481

Trial Description

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Title

A 24-week, Phase IIB, Randomized, Active-controlled, Parallel Group, Multi-center Study to Evaluate the Safety and Efficacy of GSK1278863 in Subjects With Anemia Associated With Chronic Kidney Diseases Who Are Not on Dialysis.

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Trial Acronym

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URL of the Trial

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Brief Summary in Lay Language

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
continue on rhEPO. 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.

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Brief Summary in Scientific Language

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Organizational Data

  •   DRKS00006481
  •   2015/03/27
  •   2013/10/24
  •   no
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Secondary IDs

  •   NCT01977573  (ClinicalTrials.gov)
  •   113747  (GlaxoSmithKline)
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Health Condition or Problem studied

  •   Anaemia
  •   D64.8 -  Other specified anaemias
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Interventions/Observational Groups

  •   Drug: GSK1278863
  •   Drug: rhEPO
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Characteristics

  •   Interventional
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  •   Randomized controlled trial
  •   Blinded
  •   patient/subject
  •   Active control
  •   Treatment
  •   Parallel
  •   II
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Primary Outcome

- Hemoglobin (Hgb) change from baseline at Week 24; time frame: Week 24; The mean change from baseline in Hgb at Week 24 in the GSK1278863 arm will be estimated. The data will be presented for Groups 1 and 2

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Secondary Outcome

- Number percentage (%) of subjects with Hgb in the target range at Week 24; time frame: Week 24; Number (%) of subjects with Hgb in target range at Week 24 and number (%) of subjects
- Number of subjects reaching pre-defined Hgb stopping criteria; time frame: Week 24
- Change from baseline in hepcidin concentration at Week 24; time frame: Week 24
- Maximum observed change from baseline in Erythropoietin (EPO); time frame: Week 4 and 20
- Maximum observed change from baseline in Vascular Endothelial Growth Factor (VEGF); time frame: Week 4 and 20
- Population pharmacokinetics; time frame: Week 4 and 20; Evaluation of population pharmacokinetic parameters of GSK1278863 and relevant metabolites. These include fixed-effect (clearance, volumes, covariate effects) and random-effect (within and between subject variability, residual variability) parameters.
- Percentage (%) of time within target range between Week 20 and 24; time frame: Week 20-24; The percentage of time in range between Weeks 20 and 24 for a subject will be calculated by dividing the total number of days that Hgb is within the target range (9.0 to 10.5 grams [g]/deciliter [dL]) while on treatment during Weeks 20 to 24 (using linear interpolation) by the total number of days the subject remained on treatment during the defined period.
- Percentage of time below target range between Week 20 and 24; time frame: Week 20-24; The percentage of time below range between Weeks 20 and 24 for a subject will be calculated by dividing the total number of days that Hgb is below the target range (9.0 to 10.5 grams [g]/deciliter [dL]) while on treatment during Weeks 20 to 24 (using linear interpolation) by the total number of days the subject remained on treatment during the defined period
- Percentage of time above target range between Week 20 and 24; time frame: Week 20-24; The percentage of time above range between Weeks 20 and 24 for a subject will be calculated by dividing the total number of days that Hgb is above the target range (9.0 to 10.5 grams [g]/deciliter [dL]) while on treatment during Weeks 20 to 24 (using linear interpolation) by the total number of days the subject remained on treatment during the defined period.
- Ferritin; time frame: Week 24; Evaluation of change from baseline for ferritin
- Transferrin; time frame: Week 24; Evaluation of change from baseline for transferrin
- Transferrin Saturation; time frame: Week 24; Evaluation of change from baseline for transferrin saturation
- Total Iron; time frame: Week 24; Evaluation of change from baseline for total iron
- Total Iron Binding Capacity (TIBC); time frame: Week 24; Evaluation of change from baseline for total iron binding capacity
- Reticulocyte Hemoglobin Content (CHr); time frame: Week 24; Evaluation of change from baseline for reticulocyte hemoglobin content

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Countries of Recruitment

  •   United States
  •   Australia
  •   Canada
  •   Czech Republic
  •   Denmark
  •   France
  •   Germany
  •   Hungary
  •   Japan
  •   Korea, Republic of
  •   Poland
  •   Russian Federation
  •   Spain
  •   Sweden
  •   United Kingdom
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Locations of Recruitment

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Recruitment

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  •   2013/10/31
  •   228
  •   Multicenter trial
  •   International
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Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   no maximum age
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Additional Inclusion 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. 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.

- Corrected QT interval (QTc): Bazett's Correction of QT Interval (QTcB) <470
milliseconds (msec) or QTcB <480 msec in subjects with bundle branch block. There is
no QTc criterion for subjects with a predominantly paced rhythm.

- CKD stage: Kidney Disease Outcomes Quality Initiative (KDOQI) CKD stages 3/4/5
defined by electronic estimated glomerular filtration rate (eGFR) using the CKD
Epidemiology Collaboration (CKD-EPI) formula.

- Hgb: Group 1 (rhEPO naïve): Baseline Hgb of 8.0-10.0 gram per deciliter (g/dL), Group
2 (rhEPO users): Baseline Hgb of 9.0-10.5 g/dL.

- Stable rhEPO dose for rhEPO users: Group 2 subjects must be using the same rhEPO
(epoetins or their biosimilars, or darbepoetin) with total weekly doses that varied
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.

- Oral iron therapy: If on oral iron, then doses must not be changed for the 4 weeks
prior to Week -4, during the screening phase, and through the first 4 weeks after
Randomization.

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Exclusion Criteria

- Dialysis: On dialysis or planning to initiate dialysis during the study.

- Renal transplant: Pre-emptive or scheduled renal transplant.

- High rhEPO dose: An epoetin dose of >=360 IU/kg/week intravenous (IV) or >=250
IU/kg/week subcutaneous (SC) or darbepoetin dose of >=1.8 microgram per kilogram per
week (mcg/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).

- IV iron therapy: Use of IV iron for 4 weeks prior to Screening Week -4, during the
screening phase, and through the first 4 weeks after Randomization

- Vitamin B12: Below the lower limit of the reference range (may rescreen in a minimum
of 8 weeks).

- Folate: <2.0 nanogram per millilitre (ng/mL) (<4.5 nanomoles per liter [nmol/L]) (may
rescreen in a minimum of 4 weeks).

- Ferritin: <40 ng/mL (<40 mcg/L).

- Transferrin saturation (TSAT): Outside of the reference range.

- 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 as diastolic blood pressure (DBP) >100 mmHg or systolic blood
pressure (SBP) >170 mmHg at Week -4 and reconfirmed at Day 1.

- 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).

- 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 [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: 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.

- Gastrointestinal (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 IV antibiotic therapy within the 8 weeks prior to Week -4 Screening through
Day 1 (randomization).

- 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).

- 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).

- Other Conditions: Any other condition, clinical or laboratory abnormality, or
examination finding that the Investigator considers would put the subject at
unacceptable risk.

- Patient participation: Unwillingness or inability of the subject to follow the
procedures or lifestyle or dietary restrictions outlined in the protocol.

- Pregnancy or Lactation: Pregnant females as determined by positive urine human
chorionic gonadotropin (hCG) test OR women who are lactating at Week -4 Screening or
during the trial.

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Addresses

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    • GlaxoSmithKline
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  • start of 1:1-Block address scientific-contact
    • GlaxoSmithKline
    • GSK Clinical Trials 
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    • US GSK Clinical Trials Call Center 
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Sources of Monetary or Material Support

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    • Bitte wenden Sie sich an den Sponsor / Please refer to primary sponsor
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Status

  •   Recruiting ongoing
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Trial Publications, Results and other Documents

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The parameters in ClinicalTrials.gov and DRKS are not identical. Therefore the data import from ClinicalTrials.gov required adjustments. For full details please see the DRKS FAQs .
  •   1
  •   2014/07/16
* This entry means the parameter is not applicable or has not been set.