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

NCT ID: NCT01977573

Last Updated: 2018-10-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 252 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-10-31
• Study Completion Date: 2015-06-15

Brief Summary

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

Conditions

Anaemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

GSK1278863

Subjects will be administered GSK1278863 QD. Starting dose will be based on data from previous studies with GSK1278863 and dose-response modelling, as well as Baseline Hgb concentration. After 4 Week of fixed dose period, dose may be adjusted to achieve Hgb 9.0 to 10.5 g/dL

Group Type: EXPERIMENTAL

GSK1278863

Intervention Type: DRUG

Film-coated tablets containing 0.5 mg, 1 mg, 2 mg, 5mg or matching placebo

Control

All subjects who are randomized to the Control arm will receive rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, to maintain Hgb levels within the target range. The decision around whether a subject requires rhEPO, selection of the type of rhEPO and rhEPO dose should be based on Investigator clinical judgment, with the historical rhEPO dose (where applicable) and the current Hgb value being considered.

Group Type: OTHER

rhEPO

Intervention Type: DRUG

Locally sourced rhEPO. All subjects who are randomized to the Control arm will receive rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, to maintain Hgb levels within the target range. The decision around whether a subject requires rhEPO, selection of the type of rhEPO and rhEPO dose should be based on Investigator clinical judgment, with the historical rhEPO dose (where applicable) and the current Hgb value being considered..

Interventions

GSK1278863

Film-coated tablets containing 0.5 mg, 1 mg, 2 mg, 5mg or matching placebo

Intervention Type: DRUG

rhEPO

Locally sourced rhEPO. All subjects who are randomized to the Control arm will receive rhEPO (epoetins or their biosimilars, or darbepoetin) as necessary per standard of care, to maintain Hgb levels within the target range. The decision around whether a subject requires rhEPO, selection of the type of rhEPO and rhEPO dose should be based on Investigator clinical judgment, with the historical rhEPO dose (where applicable) and the current Hgb value being considered..

Intervention Type: DRUG

Eligibility Criteria

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 8.0-11.0 g/dL (inclusive) (USA sites only: 8.0-10.0 g/dL, inclusive); Group 2 (rhEPO users): Baseline Hgb of 9.0-11.5 g/dL (inclusive) (USA sites only: 9.0-10.5, inclusive).
• 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.

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): Below the lower limit 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).
• Uncontrolled 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).
• 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.
• 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 (see GSK1278863 IB for list of excipients and rhEPO (refer to local product labelling for details).
• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Kitchener, Ontario, Canada

GSK Investigational Site

London, Ontario, Canada

GSK Investigational Site

Mississauga, Ontario, Canada

GSK Investigational Site

Montreal, Quebec, Canada

GSK Investigational Site

Peoria, Arizona, United States

GSK Investigational Site

Azusa, California, United States

GSK Investigational Site

La Mesa, California, United States

GSK Investigational Site

Laguna Hills, California, United States

GSK Investigational Site

Los Angeles, California, United States

GSK Investigational Site

Los Angeles, California, United States

GSK Investigational Site

San Diego, California, United States

GSK Investigational Site

San Dimas, California, United States

GSK Investigational Site

West Hills, California, United States

GSK Investigational Site

Lauderdale Lakes, Florida, United States

GSK Investigational Site

Miami, Florida, United States

GSK Investigational Site

Pembroke Pines, Florida, United States

GSK Investigational Site

Macon, Georgia, United States

GSK Investigational Site

Savannah, Georgia, United States

GSK Investigational Site

Evergreen Park, Illinois, United States

GSK Investigational Site

Shreveport, Louisiana, United States

GSK Investigational Site

Farmington, Missouri, United States

GSK Investigational Site

Charlotte, North Carolina, United States

GSK Investigational Site

Bethlehem, Pennsylvania, United States

GSK Investigational Site

Uniontown, Pennsylvania, United States

GSK Investigational Site

Knoxville, Tennessee, United States

GSK Investigational Site

Corsicana, Texas, United States

GSK Investigational Site

San Antonio, Texas, United States

GSK Investigational Site

Temple, Texas, United States

GSK Investigational Site

Salt Lake City, Utah, United States

GSK Investigational Site

Liverpool, New South Wales, Australia

GSK Investigational Site

Westmead, New South Wales, Australia

GSK Investigational Site

Adelaide, South Australia, Australia

GSK Investigational Site

Nedlands, Western Australia, Australia

GSK Investigational Site

Edmonton, Alberta, Canada

GSK Investigational Site

Brampton, Ontario, Canada

GSK Investigational Site

Greater Sudbury, Ontario, Canada

GSK Investigational Site

Pointe-Claire, Quebec, Canada

GSK Investigational Site

Cheb, , Czechia

GSK Investigational Site

Liberec, , Czechia

GSK Investigational Site

Louny, , Czechia

GSK Investigational Site

Mariánské Lázně, , Czechia

GSK Investigational Site

Most, , Czechia

GSK Investigational Site

Prague, , Czechia

GSK Investigational Site

Prague, , Czechia

GSK Investigational Site

Prague, , Czechia

GSK Investigational Site

Sokolov, , Czechia

GSK Investigational Site

Odense C, , Denmark

GSK Investigational Site

Roskilde, , Denmark

GSK Investigational Site

Amiens, , France

GSK Investigational Site

Bordeaux, , France

GSK Investigational Site

Caen, , France

GSK Investigational Site

Créteil, , France

GSK Investigational Site

Lyon, , France

GSK Investigational Site

Paris, , France

GSK Investigational Site

Sainte-Foy-lès-Lyon, , France

GSK Investigational Site

Mannheim, Baden-Wurttemberg, Germany

GSK Investigational Site

Ulm, Baden-Wurttemberg, Germany

GSK Investigational Site

Munich, Bavaria, Germany

GSK Investigational Site

Demmin, Mecklenburg-Vorpommern, Germany

GSK Investigational Site

Düsseldorf, North Rhine-Westphalia, Germany

GSK Investigational Site

Leipzig, Saxony, Germany

GSK Investigational Site

Berlin, , Germany

GSK Investigational Site

Hamburg, , Germany

GSK Investigational Site

Budapest, , Hungary

GSK Investigational Site

Budapest, , Hungary

GSK Investigational Site

Budapest, , Hungary

GSK Investigational Site

Budapest, , Hungary

GSK Investigational Site

Székesfehérvár, , Hungary

GSK Investigational Site

Aichi, , Japan

GSK Investigational Site

Gifu, , Japan

GSK Investigational Site

Gunma, , Japan

GSK Investigational Site

Ibaraki, , Japan

GSK Investigational Site

Ibaraki, , Japan

GSK Investigational Site

Kanagawa, , Japan

GSK Investigational Site

Kyoto, , Japan

GSK Investigational Site

Nagano, , Japan

GSK Investigational Site

Osaka, , Japan

GSK Investigational Site

Shiga, , Japan

GSK Investigational Site

Krakow, , Poland

GSK Investigational Site

Lublin, , Poland

GSK Investigational Site

Tarnów, , Poland

GSK Investigational Site

Warsaw, , Poland

GSK Investigational Site

Zabrze, , Poland

GSK Investigational Site

Izhevsk, , Russia

GSK Investigational Site

Kaluga, , Russia

GSK Investigational Site

Khantymansiysk, , Russia

GSK Investigational Site

Krasnodar, , Russia

GSK Investigational Site

Krasnoyarsk, , Russia

GSK Investigational Site

Moscow, , Russia

GSK Investigational Site

Moscow, , Russia

GSK Investigational Site

Saint Petersburg, , Russia

GSK Investigational Site

Ulyanovsk, , Russia

GSK Investigational Site

Yaroslavl, , Russia

GSK Investigational Site

Anyang-Si Gyeonggi-do, , South Korea

GSK Investigational Site

Daegu, , South Korea

GSK Investigational Site

Daejeon, , South Korea

GSK Investigational Site

Gwangju, , South Korea

GSK Investigational Site

Alcalá de Henares, , Spain

GSK Investigational Site

Badalona, , Spain

GSK Investigational Site

Barcelona, , Spain

GSK Investigational Site

Barcelona, , Spain

GSK Investigational Site

Barcelona, , Spain

GSK Investigational Site

Córdoba, , Spain

GSK Investigational Site

Granada, , Spain

GSK Investigational Site

Madrid, , Spain

GSK Investigational Site

Madrid, , Spain

GSK Investigational Site

San Sebastián de los Reyes, , Spain

GSK Investigational Site

Santander, , Spain

GSK Investigational Site

Santiago de Compostela, , Spain

GSK Investigational Site

Gothenburg, , Sweden

GSK Investigational Site

Karlstad, , Sweden

GSK Investigational Site

Örebro, , Sweden

GSK Investigational Site

Stockholm, , Sweden

GSK Investigational Site

Uppsala, , Sweden

GSK Investigational Site

Chelmsford, , United Kingdom

GSK Investigational Site

Dorchester, , United Kingdom

GSK Investigational Site

Dundee, , United Kingdom

GSK Investigational Site

Hull, , United Kingdom

GSK Investigational Site

Leeds, , United Kingdom

GSK Investigational Site

London, , United Kingdom

GSK Investigational Site

London, , United Kingdom

GSK Investigational Site

Manchester, , United Kingdom

GSK Investigational Site

Oxford, , United Kingdom

Countries

United States; Australia; Canada; Czechia; Denmark; France; Germany; Hungary; Japan; Poland; Russia; South Korea; Spain; Sweden; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 36005278 (View on PubMed)

Other Identifiers

113747

Identifier Type: -

Identifier Source: org_study_id