Study to Evaluate the Efficacy, Safety and Pharmacokinetics of Three-times Weekly Dosing of GSK1278863 in Hemodialysis-dependent Subjects With Anemia Associated With Chronic Kidney Disease Who Are Switched From a Stable Dose of an Erythropoiesis-stimulating Agent

NCT02689206 | Completed Phase 2 Results

• 2 other identifiers: 2048362015-004790-32
• Study Type: interventional
• Target: 103
• Locations: 5 countries
• Sites: 38

Brief Summary

GSK1278863 is an orally available, hypoxia-inducible factor - prolyl hydroxylase inhibitor, currently being investigated as a treatment for anemia associated with chronic kidney disease. GSK1278863 has been given as a once daily regimen in clinical studies to date. However, physicians in countries that use a three-times weekly hemodialysis schedule prefer to give the anemia medicine at the same time as the dialysis session. This study will test how well GSK1278863 can maintain hemoglobin levels when given three-times weekly, for 29 days. This study will describe the relationship between hemoglobin and GSK1278863 given three-times weekly. The data from this study will allow for conversion of once daily doses to three-times weekly doses.

Conditions

Anaemia

Keywords

Chronic kidney disease; Efficacy; Erythropoiesis-stimulating agent; GSK1278863; Safety; Hemodialysis-dependent anemia; Pharmacokinetics

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Hgb Levels at Day 29

  Blood samples were collected from participants for measurement of Hgb values. Baseline is the average of Hgb measured at Week -2 and Day 1 visits. Change from Baseline at Day 29 was defined as post dose value at Day 29 minus Baseline value. The analysis was performed on intent-to-treat (ITT) Population which comprised of all randomized participants who received at least one dose of study treatment, had a Baseline and at least one corresponding on treatment assessment, including Hgb.

  Baseline and Day 29

Secondary Outcomes (39)

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

  Baseline and up to Day 29

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

  Baseline and up to Day 29

• Percent Change From Baseline in Hepcidin at Day 29

  Baseline and Day 29

• Change From Baseline in Hematocrit Levels

  Baseline and Day 29

• Change From Baseline in Red Blood Cell (RBC) Count

  Baseline and Day 29

Study Arms (5)

GSK1278863 10 mg

EXPERIMENTAL

Subject will receive 10 mg of GSK1278863 three-times weekly for 4 weeks (up to 29 days).

Drug: GSK1278863

GSK1278863 15 mg

EXPERIMENTAL

Subject will receive 15 mg of GSK1278863 three-times weekly for 4 weeks (up to 29 days).

Drug: GSK1278863

GSK1278863 25 mg

EXPERIMENTAL

Subject will receive 25 mg of GSK1278863 three-times weekly for 4 weeks (up to 29 days).

Drug: GSK1278863

GSK1278863 30 mg

EXPERIMENTAL

Subject will receive 30 mg of GSK1278863 three-times weekly for 4 weeks (up to 29 days).

Drug: GSK1278863

Placebo

PLACEBO COMPARATOR

Subject will receive GSK1278863 matching placebo three-times weekly for 4 weeks (up to 29 days).

Drug: GSK1278863 matching Placebo

Interventions

GSK1278863 DRUG

GSK1278863 will be supplied as a round, biconvex, 10 millimeter (mm) white film coated tablet with the unit dose strength of 5 mg and 25 mg.

GSK1278863 10 mg; GSK1278863 15 mg; GSK1278863 25 mg; GSK1278863 30 mg

GSK1278863 matching Placebo DRUG

GSK1278863 matching placebo will be supplied as a round, biconvex, 10 mm white film coated tablet.

Placebo

Eligibility Criteria

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

You may qualify if:

• More than or equal to 18 years of age, at the time of signing the informed consent.
• Hemoglobin: Stable Hemoglobin 9.0 - 11.5 gram per deciliter (g/dL).
• Dialysis frequency: On hemodialysis (HD, hemofiltration or hemodiafiltration) three to five times weekly for at least 4 weeks prior to Day -28 Screening through Day 29.
• Dialysis adequacy: A single pool Kt/Vurea of \>=1.2 based on a historical value obtained within the prior three months 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 percent. NOTE: Only needs confirming at Day -28.
• Erythropoiesis-stimulating agent (ESA)dose: Treated with the same ESA (epoetins or their biosimilars, or darbepoetin or methoxy polyethylene glycol \[PEG\]-epoetin beta) with total weekly dose varying by no more than 50 percent during the 4 weeks prior to Day -28.
• Iron replacement therapy: Subjects may be on stable maintenance oral or intravenous (IV) (\<=100 milligram (mg)/week) iron supplementation. If subjects are on oral or IV iron, then doses must be stable for the 4 weeks prior to Day -28, during the screening phase, and through the 29 days of treatment.
• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the consent form and in study protocol.

You may not qualify if:

• Dialysis modality: Planned change from HD to peritoneal dialysis within the study time period.
• Renal transplant: Planned for living-related kidney transplant.
• High ESA dose: An epoetin dose of \>=360 international unit (IU)/kilogram (kg)/week IV or \>=250 IU/kg/week subcutaneous (SC) or darbepoetin dose of \>=1.8 microgram (mcg)/kg/week IV or SC or methoxy PEG-epoetin beta dose of \>= 2.2 mcg/kg/week within the prior 8 weeks through Day 1 (randomization).
• Administration of methoxy PEG-epoetin beta within the prior 4 weeks through Day 1 (randomization).
• Myocardial infarction or acute coronary syndrome: Within the 8 weeks prior to Screening through Day 1 (randomization).
• Stroke or transient ischemic attack: Within 8 weeks prior to Screening though Day 1 (randomization).
• Heart failure: Class IV heart failure, as defined by the New York Heart Association (NYHA) functional classification system diagnosed prior to 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 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 of chronic disease other than renal disease diagnosed prior to Screening though 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 \[alanine transaminase (ALT) or aspartate transaminase (AST) \>2x upper limit of normal (ULN) or total bilirubin \>1.5xULN\]; or other hepatic abnormalities that in the opinion of the investigator would preclude the subject from participating in the study.
• Major surgery: Major surgery (excluding vascular access surgery) within the 8 weeks prior to Screening, during the Screening phase, or planned during the study.
• Transfusion: Blood transfusion within the 8 weeks prior to Screening, during the 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 Screening through Day 1 (randomization).
• Acute Infection: Clinical evidence of acute infection or history of infection requiring IV antibiotic therapy within the 4 weeks prior to Screening through Day 1 (randomization). NOTE: IV antibiotics as prophylaxis are allowed.
• Malignancy: History of malignancy within the two years prior to randomization or currently receiving treatment for cancer, or has a known \>=4 centimeter complex kidney cyst (i.e. Bosniak Category II F, III of IV). NOTE: ONLY exception is squamous cell or basal cell carcinoma of the skin that has been definitively treated \>=8 weeks prior to Screening.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (38)

GSK Investigational Site

Northridge, California, 91324, United States

Location

GSK Investigational Site

San Dimas, California, 91773, United States

Location

GSK Investigational Site

Pembroke Pines, Florida, 33028, United States

Location

GSK Investigational Site

Greenbelt, Maryland, 20770, United States

Location

GSK Investigational Site

Roseville, Michigan, 48066, United States

Location

GSK Investigational Site

Kansas City, Missouri, 64111, United States

Location

GSK Investigational Site

The Bronx, New York, 10461, United States

Location

GSK Investigational Site

Calgary, Alberta, T2R 0X7, Canada

Location

GSK Investigational Site

Ottawa, Ontario, K1H 7W9, Canada

Location

GSK Investigational Site

Toronto, Ontario, M3M 0B2, Canada

Location

GSK Investigational Site

Greenfield Park, Quebec, J4V 2H1, Canada

Location

GSK Investigational Site

Stuttgart, Baden-Wurttemberg, 70376, Germany

Location

GSK Investigational Site

Villingen-Schwenningen, Baden-Wurttemberg, 78054, Germany

Location

GSK Investigational Site

Kiel, Schleswig-Holstein, 24105, Germany

Location

GSK Investigational Site

Darmstadt, 64295, Germany

Location

GSK Investigational Site

Krasnodar, 350029, Russia

Location

GSK Investigational Site

Moscow, 129327, Russia

Location

GSK Investigational Site

Mytischi, 141009, Russia

Location

GSK Investigational Site

Omsk, 644112, Russia

Location

GSK Investigational Site

Penza, 440034, Russia

Location

GSK Investigational Site

Saint Petersburg, 194354, Russia

Location

GSK Investigational Site

Saint Petersburg, 197110, Russia

Location

GSK Investigational Site

Yaroslavl, 150062, Russia

Location

GSK Investigational Site

Almería, 04009, Spain

Location

GSK Investigational Site

Badalona, 08916, Spain

Location

GSK Investigational Site

Barcelona, 08003, Spain

Location

GSK Investigational Site

Granollers, Barcelona, 08041, Spain

Location

GSK Investigational Site

L'Hospitalet de Llobregat, 08907, Spain

Location

GSK Investigational Site

Lleida, 25198, Spain

Location

GSK Investigational Site

Madrid, 28040, Spain

Location

GSK Investigational Site

Madrid, 28041, Spain

Location

GSK Investigational Site

Madrid, 28100, Spain

Location

GSK Investigational Site

Manises (Valencia), 46940, Spain

Location

GSK Investigational Site

Málaga, 29010, Spain

Location

GSK Investigational Site

San Sebastián de los Reyes, 28702, Spain

Location

GSK Investigational Site

Santander, 39008, Spain

Location

GSK Investigational Site

Santiago de Compostela, 15706, Spain

Location

GSK Investigational Site

Valladolid, 47005, Spain

Location

Related Publications (2)

• Bailey CK, Caltabiano S, Cobitz AR, Huang C, Mahar KM, Patel VV. A randomized, 29-day, dose-ranging, efficacy and safety study of daprodustat, administered three times weekly in patients with anemia on hemodialysis. BMC Nephrol. 2019 Oct 16;20(1):372. doi: 10.1186/s12882-019-1547-z.

  PMID: 31619187 BACKGROUND

• 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

GSKClinicalSupportHD@gsk.com

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: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 11, 2016
• First Posted: February 23, 2016
• Study Start: February 17, 2016
• Primary Completion: January 25, 2017
• Study Completion: January 25, 2017
• Last Updated: February 25, 2020
• Results First Posted: May 21, 2018

Record last verified: 2020-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD is available via the Clinical Study Data Request site (click on the link provided below)
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

Locations

US (7); CA (4); RU (8); ES (15); DE (4)