A 24-week, Phase 2B, randomized, active-controlled, parallel group, multi-center study to evaluate the safety and efficacy of GSK1278863 in subjects with anemia associated with chronic kidney disease who are not on dialysis
- Conditions
- Anemia associated with chronic kidney diseaseMedDRA version: 16.1Level: LLTClassification code 10064848Term: Chronic kidney diseaseSystem Organ Class: 100000004857Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]
- Registration Number
- EUCTR2013-002681-39-HU
- Lead Sponsor
- GlaxoSmithKline Research and development
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 252
General criteria (Week -4 verification only)
1. Age: >or=18 years of age.
2. Gender: Female and male subjects
•Females: If of childbearing potential, must agree to use one of the approved contraception methods as outlined in Section 11.6 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 IU/L and estradiol •Males: must agree to use one of the approved contraceptive methods as outlined in Section 11.6 from the time of Screening until completion of the Follow-up Visit.
3. QTc: QTcB <470 msec or QTcB <480 msec in subjects with bundle branch block.
There is no QTc criterion for subjects with a predominantly paced rhythm.
CKD-related criteria
4. CKD stage: Kidney Disease Outcomes Quality Initiative (KDOQI) CKD stages 3/4/5 defined by eGFR using the CKD Epidemiology Collaboration (CKD-EPI) formula. The exception is that the Japanese Society of Nephrology-Chronic Kidney Disease Initiatives (JSN-CKDI) equation will be used for Japanese subjects from (or recruited at) Japan sites.
5. Hemoglobin: See Section 4.2 for details
a. Group 1 (rhEPO naïve): Baseline Hgb of 8.0-10.0 g/dL.
b. Group 2 (rhEPO users): Baseline Hgb of 9.0-10.5 g/dL.
6. rhEPO user:
Group 1: No current or prior rhEPO use within the past 8 weeks; e.g.,
epoetins (or their biosimilars), darbepoetin, Mircera (methoxy
polyethylene glycol epoetin beta), or their biosimilars.
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.
7. 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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 200
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 28
Subjects are not eligible if they meet any of the following criteria.
CKD-related criteria
1. Dialysis: On dialysis or planning to initiate dialysis during the study
2. Renal transplant: Pre-emptive or scheduled renal transplant
3. High rhEPO dose: An epoetin dose of >or=360 IU/kg/week IV or darbepoetin dose of >or=1.8 µg/kg/week IV within the prior 8 weeks through Day 1
4. Mircera: Use of Mircera (methoxy polyethylene glycol epoetin beta) within the
prior 8 weeks through Day 1
5. 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 Laboratory test-based criteria (Week -4 verification only)
6. Vitamin B12: Below the lower limit of the reference range
7. Folate: <2.0 ng/mL (<4.5 nmol/L) (may rescreen in a minimum of 4 weeks
8. Ferritin: <40 ng/mL (<40 ug/L)
9. Transferrin saturation (TSAT): Outside of the reference range Cardiovascular disease-related criteria
10. Myocardial infarction or acute coronary syndrome: Within the 8 weeks prior to
Screening through Day 1
11. Stroke or transient ischemic attack: Within the 8 weeks prior to Week -4
Screening through Day 1
12. 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
- Symptomatic right heart failure diagnosed prior to Week -4 Screening through Day 1
13. Hypertension: Defined as DBP >100 mmHg or SBP>170 mmHg at Week -4 and reconfirmed at Day 1
14. Thrombotic Disease: History of thrombotic disease, except vascular access thrombosis within the 8 weeks prior to Week -4 Screening through Day 1
Other disease-related criteria
15. Ophthalmology disease: Meeting any ophthalmologic-related exclusion criteria determined at the Screening ophthalmology exam
16. Inflammatory disease: Active chronic inflammatory disease that could impact
erythropoiesis diagnosed prior to Week -4 Screening through Day 1
17. Hematological disease: Any hematological disease including those affecting platelets, white or red blood cells, coagulation disorders, or any other cause of anemia other than renal disease diagnosed prior to Week -4 Screening through Day 1
18. Liver disease: Current liver disease, known hepatic or biliary abnormalities 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.
19. Major surgery: Major surgery within the prior 8 weeks, during the Week -4 Screening phase or planned during the study
20. Transfusion: Blood transfusion within the prior 8 weeks, during the Week -4 Screening phase or an anticipated need for blood transfusion during the study
21. 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
22. 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
23. Malignancy: Subjects with a history of malignancy within the prior 5 years, who receiving treatment for cancer, or who have a strong famil
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method