4 Week Switch Study in Hemodialysis-dependent Subjects With Anemia Associated With Chronic Kidney Disease

NCT01587924 | Completed Phase 2 Results

• 1 other identifier: 116582
• Study Type: interventional
• Target: 80
• Locations: 6 countries
• Sites: 62

Brief Summary

This is a four-week, Phase IIa, randomized, active-controlled, parallel-group, multi-center study to evaluate the safety, efficacy and pharmacokinetics of switching subjects from stable rhEPO to GSK1278863 in approximately 68 hemodialysis-dependent subjects with anemia associated with chronic kidney disease. The study consists of a screening phase of 2 weeks, a 4-week treatment phase and a 2-week follow-up phase. The range of Hgb values for study eligibility is 9.5-12.0 g/dL and the subjects must have received the same rhEPO product with total weekly doses that varied by no more than 50% during the 4 weeks prior to the Screening visit (Week -1. This study aims to estimate the relationship between dose of GSK1278863 and Hgb response in hemodialysis-dependent (HDD) subjects with anemia associated with chronic kidney disease after switching from a stable maintenance dose of recombinant human erythropoetin (rhEPO).

Conditions

Anaemia

Keywords

Renal Impairment; Anemia; pharmacokinetics; hemodialysis; Chronic kidney disease; GSK1278863; hemoglobin; Prolyl hydroxylase inhibitor; recombinant human erythropoietin; erythropoiesis stimulating agents; Dialysis, Renal

Outcome Measures

Primary Outcomes (1)

• Modeled Hemoglobin (Hgb) Change From Baseline (Pre-dose on Day 1) at 4 Weeks of Treatment

  Modeled Hgb change from Baseline over 4 weeks of treatment. Change from Baseline is the actual value of Hgb at Week 4 minus the Baseline value. For modeled change at Week 4 participants required a Baseline and two or more non missing post-baseline values. Baseline is the average of Week -2, -1 and Day 1 values. The model included fixed effects for Baseline Hgb, treatment, and treatment by day interaction. Covariate analysis for modeled Hgb change was performed. Random effects were fitted in the intercept and the slope over time.

  Baseline (pre-dose on Day 1) and up to week 4

Secondary Outcomes (22)

• Hgb Variability Over 4 Weeks

  Up to 4 weeks

• Evaluation of Change From Baseline in Hepcidin Over Period

  Baseline (pre-dose on Day 1) and up to 4 weeks

• Evaluation of Change From Baseline (Pre-dose on Day 1) in High Sensitivity C-Reactive Protein (hsCRP) Over 4 Weeks

  Baseline (pre-dose on Day 1) and up to 4 weeks

• Change From Baseline for Erythropoeitin (EPO) Over Period

  Baseline (pre-dose on Day 1) and up to 4 weeks

• Evaluation of Change From Baseline (Pre-dose on Day 1) for Peak Vascular Endothelial Growth Factor (VEGF) Over 4 Weeks

  Baseline (pre-dose on Day 1) and up to 4 weeks

Study Arms (4)

0.5 mg GSK1278863

EXPERIMENTAL

once daily

Drug: GSK1278863

2 mg GSK1278863

EXPERIMENTAL

once daily

Drug: GSK1278863

5 mg GSK1278863

EXPERIMENTAL

once daily

Drug: GSK1278863

rhEPO

ACTIVE COMPARATOR

as required

Drug: rhEPO

Interventions

GSK1278863 DRUG

tablet

0.5 mg GSK1278863; 2 mg GSK1278863; 5 mg GSK1278863

rhEPO DRUG

injection

rhEPO

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 and weight: \>/=18 years of age and \>/=45 kg (weight post-dialysis).
• On three times weekly hemodialysis for at least 8 weeks, irrespective of eGFR values and stage of chronic kidney disease (CKD).
• A single-pool Kt/Vurea of \>/=1.2 based on a historical value obtained within the prior month 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%.
• rhEPO use: Using the same rhEPO (epoetins or darbepoetin) with total weekly doses that varied by no more than 50% during the prior 4 weeks (i.e., maximum vs. minimum total weekly doses \</=50%).
• Hgb concentrations 9.5-12.0 g/dL (inclusive).
• Vitamin B12 above the lower limit of the reference range (may rescreen in two months).
• Folate: \>/= 2.0 ng/mL (may rescreen in one month).
• Ferritin: \>/=40 ng/mL with the absence of microcytic or hypochromic RBCs.
• Transferrin saturation (TSAT): Within the reference range.
• Iron replacement therapy: Stable maintenance dose of oral iron replacement therapy, if required, that will be maintained throughout the study. NOTE: IV iron replacement therapy is not allowed the two weeks prior to Screening through the end of the study (Week 6).
• QTc: QTcB \<470 msec or QTcB \<480 msec in subjects with bundle branch block obtained at Screening Visit (based on Central Reader's interpretation).
• Females: Eligible to participate if she is of childbearing potential, and 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 of hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea \[in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH)\>40MIU/ml and estradiol \<40pg/ml is confirmatory\]. 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. For most forms of HRT, at least 2 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method.
• Males: Must agree to use one of the approved contraceptive methods from the time of Screening until completion of the Follow-up Visit.

You may not qualify if:

• Dialysis modality: On peritoneal dialysis OR planned change in dialysis modality within the study time period.
• rhEPO Hyporesponders: As defined by an epoetin dose of \>/=360 IU/kg/week IV or darbepoetin dose of \>/=1.8 µg/kg/week IV within the prior 8 weeks.
• Renal transplant: Renal transplant anticipated or scheduled within the study time period or subjects with a functioning renal transplant.
• Mircera or Peginesatide: Current or prior use (within the prior 8 weeks) of Mircera (methoxy polyethylene glycol epoetin beta) OR peginesatide.
• Total CPK: \>5x the upper limit of the reference range.
• HIV: Positive HIV antibody.
• History of myocardial infarction or acute coronary syndrome within the prior 6 months.
• History of stroke or transient ischemic attacks (TIAs) within the prior 6 months.
• Heart failure: Class III/IV heart failure, as defined by the New York Heart Association (NYHA) functional classification system.
• Hypertension: Poorly controlled hypertension, whether due to inadequate treatment, or lack of treatment, is defined as follows:
• DBP \>100 mmHg or SBP\>160 mmHg for subjects taking hypertension medication(s) before screening and dialysis, if required.
• DBP \>105 mmHg or SBP\>170 mmHg for subjects who are asked to hold hypertension medication(s) before screening and dialysis.
• 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), or other thrombosis related condition except shunt thrombosis) within the prior 6 months.
• Pulmonary hypertension: Known pulmonary hypertension and those at higher risk (than normally associated with CKD) for pre-existing elevation in pulmonary pressure (e.g., significant heart failure or lung disease requiring supplemental oxygen, or those with connective tissue diseases).
• Inflammatory disease: Chronic inflammatory disease that could impact erythropoiesis (e.g., scleroderma, systemic lupus erythematosis, rheumatoid arthritis, celiac disease).

Sponsors & Collaborators

• GlaxoSmithKline: lead
• PPD Development, LP: collaborator

Study Sites (62)

GSK Investigational Site

Paragould, Arizona, 72450, United States

Location

GSK Investigational Site

Tempe, Arizona, 85284, United States

Location

GSK Investigational Site

Pine Bluff, Arkansas, 71603, United States

Location

GSK Investigational Site

Azusa, California, 91702, United States

Location

GSK Investigational Site

Bakersfield, California, 93308, United States

Location

GSK Investigational Site

Bakersfield, California, 93309, United States

Location

GSK Investigational Site

Los Angeles, California, 90022, United States

Location

GSK Investigational Site

Los Angeles, California, 90025-4837, United States

Location

GSK Investigational Site

Los Angeles, California, 90057, United States

Location

GSK Investigational Site

Lynwood, California, 60262, United States

Location

GSK Investigational Site

Orange, California, 92868, United States

Location

GSK Investigational Site

Riverside, California, 92505, United States

Location

GSK Investigational Site

West Hills, California, 91307, United States

Location

GSK Investigational Site

Whittier, California, 90603, United States

Location

GSK Investigational Site

Arvada, Colorado, 80002, United States

Location

GSK Investigational Site

Denver, Colorado, 80230, United States

Location

GSK Investigational Site

Westminster, Colorado, 80031, United States

Location

GSK Investigational Site

Waterbury, Connecticut, 06708, United States

Location

GSK Investigational Site

Coral Springs, Florida, 33071, United States

Location

GSK Investigational Site

Miami, Florida, 33145, United States

Location

GSK Investigational Site

Miami, Florida, 33150, United States

Location

GSK Investigational Site

Pembroke Pines, Florida, 33028, United States

Location

GSK Investigational Site

Spring Hill, Florida, 34608, United States

Location

GSK Investigational Site

Macon, Georgia, 31217, United States

Location

GSK Investigational Site

Gurnee, Illinois, 60031, United States

Location

GSK Investigational Site

Bethesda, Maryland, 20814, United States

Location

GSK Investigational Site

Detroit, Michigan, 48236, United States

Location

GSK Investigational Site

Southgate, Michigan, 48195, United States

Location

GSK Investigational Site

Las Vegas, Nevada, 89106, United States

Location

GSK Investigational Site

Brooklyn, New York, 11212, United States

Location

GSK Investigational Site

Asheville, North Carolina, NC 28805, United States

Location

GSK Investigational Site

Charlotte, North Carolina, United States

Location

GSK Investigational Site

Durham, North Carolina, 27704, United States

Location

GSK Investigational Site

Winston-Salem, North Carolina, 27101, United States

Location

GSK Investigational Site

Oklahoma City, Oklahoma, 73116, United States

Location

GSK Investigational Site

Erie, Pennsylvania, 16507, United States

Location

GSK Investigational Site

Arlington, Texas, 76011, United States

Location

GSK Investigational Site

Greenville, Texas, 75402, United States

Location

GSK Investigational Site

Houston, Texas, 77004, United States

Location

GSK Investigational Site

Houston, Texas, 77091, United States

Location

GSK Investigational Site

Killeen, Texas, TX 76543, United States

Location

GSK Investigational Site

San Antonio, Texas, 78229, United States

Location

GSK Investigational Site

Calgary, Alberta, T2R 0X7, Canada

Location

GSK Investigational Site

Edmonton, Alberta, T6G 2B7, Canada

Location

GSK Investigational Site

Halifax, Nova Scotia, B3H 1V7, Canada

Location

GSK Investigational Site

Greater Sudbury, Ontario, P3E 5J1, Canada

Location

GSK Investigational Site

London, Ontario, N6A 5A5, Canada

Location

GSK Investigational Site

Aalborg, DK-9000, Denmark

Location

GSK Investigational Site

Odense, DK-5000, Denmark

Location

GSK Investigational Site

Roskilde, DK-4000, Denmark

Location

GSK Investigational Site

Heidelberg, Baden-Wurttemberg, 69120, Germany

Location

GSK Investigational Site

Aschaffenburg, Bavaria, 63741, Germany

Location

GSK Investigational Site

Oberschleißheim, Bavaria, 85764, Germany

Location

GSK Investigational Site

Lehrte, Lower Saxony, 31275, Germany

Location

GSK Investigational Site

Demmin, Mecklenburg-Vorpommern, 17109, Germany

Location

GSK Investigational Site

Cologne, North Rhine-Westphalia, 50937, Germany

Location

GSK Investigational Site

Hamburg, 22297, Germany

Location

GSK Investigational Site

Oslo, 0027, Norway

Location

GSK Investigational Site

Oslo, 0405, Norway

Location

GSK Investigational Site

Karlstad, SE-651 85, Sweden

Location

GSK Investigational Site

Stockholm, SE-141 86, Sweden

Location

GSK Investigational Site

Uppsala, SE-751 85, Sweden

Location

Related Publications (2)

• 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

• Holdstock L, Meadowcroft AM, Maier R, Johnson BM, Jones D, Rastogi A, Zeig S, Lepore JJ, Cobitz AR. Four-Week Studies of Oral Hypoxia-Inducible Factor-Prolyl Hydroxylase Inhibitor GSK1278863 for Treatment of Anemia. J Am Soc Nephrol. 2016 Apr;27(4):1234-44. doi: 10.1681/ASN.2014111139. Epub 2015 Oct 22.

  PMID: 26494831 DERIVED

Related Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

MeSH Terms

Conditions

Anemia; Renal Insufficiency; Renal Insufficiency, Chronic

Interventions

GSK1278863

Condition Hierarchy (Ancestors)

Hematologic Diseases; Hemic and Lymphatic Diseases; 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: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 23, 2012
• First Posted: April 30, 2012
• Study Start: May 23, 2012
• Primary Completion: May 27, 2013
• Study Completion: May 27, 2013
• Last Updated: November 14, 2017
• Results First Posted: September 12, 2017

Record last verified: 2017-08

Data Sharing

• IPD Sharing: Will share

Locations

US (42); CA (5); DK (3); DE (7); SE (3); NO (2)