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

NCT01977573 | Completed Phase 2 Results DMC

• 1 other identifier: 113747
• Study Type: interventional
• Target: 252
• Locations: 15 countries
• Sites: 123

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

Keywords

Prolyl hydroxylase inhibitor; pharmacokinetics; GSK1278863; Anemia; hemoglobin; erythropoiesis stimulating agents; Chronic kidney disease

Outcome Measures

Primary Outcomes (1)

• Summary of Hemoglobin (Hgb) Concentration at Week 24

  The original Hgb Criteria for Group 1- rhEPO naive participants with a stable baseline Hgb of 8.0-10.0 g/dL (8.0-10.0 g/dL USA site only) and for Group 2- rhEPO users with a stable baseline Hgb of 9.0-10.5 g/dL (9.0-10.5 g/dL USA site only); the Hgb target range was 9.0 to 10.5 g/dL (9.0-10.5 g/dL USA site only). The study amended Hgb Criteria for Group 1- rhEPO naive participants with a stable baseline Hgb of 8.0-11.0 g/dL and Group 2- rhEPO users with a stable baseline Hgb of 9.0-11.5 g/dL; Hgb target range - 10.0 to 11.5 g/dL. Data are presented for those participants following the original criteria ("Original") and those following the amended ("Amended") criteria. The primary objective was to characterize the ability of GSK1278863 to achieve mean Hgb response within the target range.

  Week 24

Secondary Outcomes (29)

• Number of Participants With Hemoglobin (Hgb) in the Target Range at Week 24

  Week 24

• Number of Participants Reaching Pre-defined Hgb Stopping Criteria

  Over a period of 24 Weeks

• Percent Change From Baseline in Hepcidin Concentration at Week 24

  Baseline and Week 24

• Maximum Observed Change From Baseline in Serum Erythropoietin (EPO)

  Baseline to Week 24

• Maximum Observed Percent Change From Baseline in Vascular Endothelial Growth Factor (VEGF)

  Baseline and up to Week 24

Study Arms (2)

GSK1278863

EXPERIMENTAL

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

Drug: GSK1278863

Control

OTHER

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.

Drug: rhEPO

Interventions

GSK1278863 DRUG

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

GSK1278863

rhEPO 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..

Control

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (123)

GSK Investigational Site

Peoria, Arizona, 85381, United States

Location

GSK Investigational Site

Azusa, California, 91702, United States

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GSK Investigational Site

La Mesa, California, 91942, United States

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GSK Investigational Site

Laguna Hills, California, 92653, United States

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GSK Investigational Site

Los Angeles, California, 90022, United States

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GSK Investigational Site

Los Angeles, California, 90025, United States

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GSK Investigational Site

San Diego, California, 92103, United States

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GSK Investigational Site

San Dimas, California, 91773, United States

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GSK Investigational Site

West Hills, California, 91307, United States

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GSK Investigational Site

Lauderdale Lakes, Florida, 33313, United States

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GSK Investigational Site

Miami, Florida, 33150, United States

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GSK Investigational Site

Pembroke Pines, Florida, 33028, United States

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GSK Investigational Site

Macon, Georgia, 31217, United States

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GSK Investigational Site

Savannah, Georgia, 31406, United States

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GSK Investigational Site

Evergreen Park, Illinois, 60805, United States

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GSK Investigational Site

Shreveport, Louisiana, 71101, United States

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GSK Investigational Site

Farmington, Missouri, 63640, United States

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GSK Investigational Site

Charlotte, North Carolina, United States

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GSK Investigational Site

Bethlehem, Pennsylvania, 18017, United States

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GSK Investigational Site

Uniontown, Pennsylvania, 15401, United States

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GSK Investigational Site

Knoxville, Tennessee, 37923, United States

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GSK Investigational Site

Corsicana, Texas, 75110, United States

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GSK Investigational Site

San Antonio, Texas, 78229, United States

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GSK Investigational Site

Temple, Texas, 76508, United States

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GSK Investigational Site

Salt Lake City, Utah, 84112, United States

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GSK Investigational Site

Liverpool, New South Wales, 2170, Australia

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GSK Investigational Site

Westmead, New South Wales, 2145, Australia

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GSK Investigational Site

Adelaide, South Australia, 5000, Australia

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GSK Investigational Site

Nedlands, Western Australia, 6009, Australia

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GSK Investigational Site

Edmonton, Alberta, T6G 2B7, Canada

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GSK Investigational Site

Brampton, Ontario, L6T 0G1, Canada

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GSK Investigational Site

Greater Sudbury, Ontario, P3E 5J1, Canada

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GSK Investigational Site

Kitchener, Ontario, N2G 1E8, Canada

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GSK Investigational Site

London, Ontario, N6A 5A5, Canada

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GSK Investigational Site

Mississauga, Ontario, L5M 2V8, Canada

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GSK Investigational Site

Montreal, Quebec, H1T 2M4, Canada

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GSK Investigational Site

Pointe-Claire, Quebec, H9R 4S3, Canada

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GSK Investigational Site

Cheb, 350 02, Czechia

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GSK Investigational Site

Liberec, 460 63, Czechia

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GSK Investigational Site

Louny, 440 01, Czechia

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GSK Investigational Site

Mariánské Lázně, 353 01, Czechia

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GSK Investigational Site

Most, 434 64, Czechia

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GSK Investigational Site

Prague, 100 34, Czechia

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GSK Investigational Site

Prague, 128 08, Czechia

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GSK Investigational Site

Prague, 142 00, Czechia

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GSK Investigational Site

Sokolov, 356 01, Czechia

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GSK Investigational Site

Odense C, 5000, Denmark

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GSK Investigational Site

Roskilde, DK-4000, Denmark

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GSK Investigational Site

Amiens, 80054, France

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GSK Investigational Site

Bordeaux, 33000, France

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GSK Investigational Site

Caen, 14033, France

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GSK Investigational Site

Créteil, 94010, France

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GSK Investigational Site

Lyon, 69437, France

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GSK Investigational Site

Paris, 75743, France

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GSK Investigational Site

Sainte-Foy-lès-Lyon, 69110, France

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GSK Investigational Site

Mannheim, Baden-Wurttemberg, 68167, Germany

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GSK Investigational Site

Ulm, Baden-Wurttemberg, 89081, Germany

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GSK Investigational Site

Munich, Bavaria, 81675, Germany

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GSK Investigational Site

Demmin, Mecklenburg-Vorpommern, 17109, Germany

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GSK Investigational Site

Düsseldorf, North Rhine-Westphalia, 40210, Germany

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GSK Investigational Site

Leipzig, Saxony, 04129, Germany

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GSK Investigational Site

Berlin, 12053, Germany

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GSK Investigational Site

Hamburg, 22297, Germany

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GSK Investigational Site

Budapest, 1036, Hungary

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GSK Investigational Site

Budapest, 1097, Hungary

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GSK Investigational Site

Budapest, 1115, Hungary

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GSK Investigational Site

Budapest, 1135, Hungary

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GSK Investigational Site

Székesfehérvár, 8000, Hungary

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GSK Investigational Site

Aichi, 455-8530, Japan

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GSK Investigational Site

Gifu, 500-8717, Japan

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GSK Investigational Site

Gunma, 370-0001, Japan

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GSK Investigational Site

Ibaraki, 302-0014, Japan

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GSK Investigational Site

Ibaraki, 302-0022, Japan

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GSK Investigational Site

Kanagawa, 210-0852, Japan

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GSK Investigational Site

Kyoto, 604-8845, Japan

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GSK Investigational Site

Nagano, 388-8004, Japan

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GSK Investigational Site

Osaka, 558-8558, Japan

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GSK Investigational Site

Shiga, 523-0082, Japan

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GSK Investigational Site

Krakow, 31-501, Poland

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GSK Investigational Site

Lublin, 20-081, Poland

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GSK Investigational Site

Tarnów, 33-100, Poland

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GSK Investigational Site

Warsaw, 02-507, Poland

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GSK Investigational Site

Zabrze, 41-800, Poland

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GSK Investigational Site

Izhevsk, 426063, Russia

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GSK Investigational Site

Kaluga, 248007, Russia

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GSK Investigational Site

Khantymansiysk, 628012, Russia

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GSK Investigational Site

Krasnodar, 350029, Russia

Location

GSK Investigational Site

Krasnoyarsk, 660062, Russia

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GSK Investigational Site

Moscow, 119121, Russia

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GSK Investigational Site

Moscow, 125101, Russia

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GSK Investigational Site

Saint Petersburg, 197110, Russia

Location

GSK Investigational Site

Ulyanovsk, 432063, Russia

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GSK Investigational Site

Yaroslavl, 150062, Russia

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GSK Investigational Site

Anyang-Si Gyeonggi-do, 431-070, South Korea

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GSK Investigational Site

Daegu, 700-721, South Korea

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GSK Investigational Site

Daejeon, 301-721, South Korea

Location

GSK Investigational Site

Gwangju, 501-757, South Korea

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GSK Investigational Site

Alcalá de Henares, 28805, Spain

Location

GSK Investigational Site

Badalona, 08916, Spain

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GSK Investigational Site

Barcelona, 08011, Spain

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GSK Investigational Site

Barcelona, 08035, Spain

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GSK Investigational Site

Barcelona, 08907, Spain

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GSK Investigational Site

Córdoba, 14004, Spain

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GSK Investigational Site

Granada, 18014, Spain

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GSK Investigational Site

Madrid, 28041, Spain

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GSK Investigational Site

Madrid, 28224, Spain

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GSK Investigational Site

San Sebastián de los Reyes, 28702, Spain

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GSK Investigational Site

Santander, 39008, Spain

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GSK Investigational Site

Santiago de Compostela, 15706, Spain

Location

GSK Investigational Site

Gothenburg, SE-413 45, Sweden

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GSK Investigational Site

Karlstad, SE-651 85, Sweden

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GSK Investigational Site

Örebro, SE-701 85, Sweden

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GSK Investigational Site

Stockholm, SE-141 86, Sweden

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GSK Investigational Site

Uppsala, SE-751 85, Sweden

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GSK Investigational Site

Chelmsford, CM1 7ET, United Kingdom

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GSK Investigational Site

Dorchester, DT1 2JY, United Kingdom

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GSK Investigational Site

Dundee, DD1 9SY, United Kingdom

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GSK Investigational Site

Hull, HU3 2JZ, United Kingdom

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GSK Investigational Site

Leeds, LS9 7TF, United Kingdom

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GSK Investigational Site

London, E1 1BB, United Kingdom

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GSK Investigational Site

London, NW3 2QG, United Kingdom

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GSK Investigational Site

Manchester, M13 9WL, United Kingdom

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GSK Investigational Site

Oxford, OX3 7LE, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 36005278 DERIVED

MeSH Terms

Conditions

Anemia; Renal Insufficiency, Chronic

Interventions

GSK1278863

Condition Hierarchy (Ancestors)

Hematologic Diseases; Hemic and Lymphatic Diseases; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 24, 2013
• First Posted: November 6, 2013
• Study Start: October 31, 2013
• Primary Completion: May 1, 2015
• Study Completion: June 15, 2015
• Last Updated: October 12, 2018
• Results First Posted: June 6, 2016

Record last verified: 2018-09

Locations

JP (10); CA (8); US (25); DK (2); DE (8); SE (5); RU (10); FR (7); HU (5); AU (4); ES (12); PL (5); GB (9); CZ (9); KR (4)