4 Week Correction Study in Subjects With Anemia Associated With Chronic Kidney Disease Who Are Not Undergoing Dialysis

NCT01587898 | Completed Phase 2 Results

• 1 other identifier: 116581
• Study Type: interventional
• Target: 72
• Locations: 3 countries
• Sites: 55

Brief Summary

This is a four-week Phase IIa, randomized, double-blind, placebo-controlled, parallel-group, multi-center study to evaluate the safety, efficacy and pharmacokinetics of GSK1278863 in approximately 68 subjects with anemia associated with chronic kidney disease who are not taking rhEPO and are not undergoing dialysis. The range of Hgb values for study eligibility is 8.5-11.0 g/dL. Eligible subjects will be randomized in equal proportions to receive once daily (QD) placebo or GSK1278863 0.5 mg, 2 mg or 5 mg in a double-blind fashion.

Conditions

Anaemia

Keywords

Anemia; Prolyl hydroxylase inhibitor; Hemoglobin; Chronic kidney disease; pharmacokinetics; recombinant human erythropoietin; GSK1278863

Outcome Measures

Primary Outcomes (1)

• Modeled Hgb Change From Baseline Over 4 Weeks of Treatment

  Modeled Hgb change from baseline over 4 weeks was derived using a random coefficient mixed effects linear regression model. The model included fixed effects for baseline Hgb, treatment and a treatment by day interaction. Random effects was fitted in the intercept and the slope over time. All data up until investigational product discontinuation was included for Hgb efficacy evaluable participants; where efficacy evaluable was defined as having a baseline and at least 2 on-treatment Hgb assessments. Baseline was the average of Week -2 , Week -1 and Day 1 visits. The change from Baseline was calculated by subtracting the Baseline value from the individual post-dose visit values.

  Baseline (average of Week -2, -1 and Day 1) and Week 4

Secondary Outcomes (42)

• Model-Adjusted Maximum Hgb Changes Over 4 Weeks

  Baseline (average of Week -2 , -1 and Day 1 visits) and 4 weeks

• Number of Participants Achieving an Increase of 0.5, 1.0, 1.5 and 2.0 g/dL in Hgb

  Up to 4 weeks

• Percentage of Participants Achieving an Increase of 0.5, 1.0, 1.5 and 2.0 g/dL in Hgb

  Up to 4 weeks

• Number of Participants Who Reached Hgb Stopping Criteria

  Up to Week 4

• Change From Baseline in Hepcidin at Week 2 and Week 4

  Baseline (Pre-dose on Day 1), Week 2 and 4

Study Arms (4)

0.5mg GSK1278863

EXPERIMENTAL

Once daily

Drug: GSK1278863

2mg GSK1278863

EXPERIMENTAL

Once daily

Drug: GSK1278863

5mg GSK1278863

EXPERIMENTAL

Once daily

Drug: GSK1278863

Placebo

EXPERIMENTAL

Once daily

Other: Placebo

Interventions

GSK1278863 DRUG

Tablet

0.5mg GSK1278863; 2mg GSK1278863; 5mg GSK1278863

Placebo OTHER

Tablet

Placebo

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.
• Not routinely undergoing dialysis, regardless of the modality (either hemodialysis or peritoneal dialysis) or dialysis planned during the time the subject would be enrolled in the study.
• No current or prior rhEPO use within the past 7 weeks; e.g., epoetins (or their biosimilars), darbepoetin, Mircera (methoxy polyethylene glycol epoetin beta), peginesatide or their biosimilars..
• KDOQI CKD stages 3/4/5 defined by eGFR using the Modification of Diet for Renal Disease (MDRD).
• Hgb: Hgb concentrations 8.5-11.0 g/dL (inclusive) as outlined in Section 4.2.
• Vitamin B12: Above the lower limit of the reference range (may rescreen in 2 months).
• Folate: \>/=2.0 ng/mL at Screening. May rescreen in a month.
• Ferritin: \>/=40 ng/mL with the absence of microcytic or hypochromic RBCs.
• 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 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 \[in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH)\>40 MIU/ml and estradiol \<40 pg/ml is confirmatory\]. 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 enrollment. For most types 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 approved contraceptive methods from the time of Screening until completion of the Follow-up Visit.

You may not qualify if:

• Dialysis: Planning to initiate dialysis during the study or who have a high potential for initiating dialysis during study participation.
• Renal transplant: Renal transplant anticipated or scheduled within the study time period or subjects with a functioning renal transplant.
• 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 TIAs.
• 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, defined as DBP \>100 mmHg or SBP\>160 mmHg.
• 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) 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).
• Hematological disease: Any hematological disease including those affecting platelets, the coagulation disorders (e.g., Protein C or S deficiency) or red blood cells (e.g. sickle cell anemia, myelodysplastic syndromes, hematological malignancy, myeloma, hemolytic anemia) or any other cause of anemia other than renal disease.
• 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 \[alkaline phosphatase, ALT or AST \> 2.0 x upper limit of normal (ULN) or total bilirubin \> 1.5 x ULN\]; or other hepatic abnormalities that in the opinion of the investigator would preclude the subject from participation in the study.
• Major surgery: Within the prior 12 weeks or planned during the study.
• Transfusion: Blood transfusion within the prior 12 weeks or an anticipated need for blood transfusion during the study.

Sponsors & Collaborators

• GlaxoSmithKline: lead
• PPD Development, LP: collaborator

Study Sites (55)

GSK Investigational Site

Azusa, California, 91702, United States

Location

GSK Investigational Site

Bakersfield, California, 93309, United States

Location

GSK Investigational Site

Chino, California, 91710, United States

Location

GSK Investigational Site

Los Angeles, California, 90022, United States

Location

GSK Investigational Site

Los Angeles, California, 90025, United States

Location

GSK Investigational Site

Los Angeles, California, 90057, United States

Location

GSK Investigational Site

North Hollywood, California, 91606-1559, United States

Location

GSK Investigational Site

Orange, California, 92868, United States

Location

GSK Investigational Site

Riverside, California, 92505, United States

Location

GSK Investigational Site

San Dimas, California, 91773, United States

Location

GSK Investigational Site

West Hills, California, 91307, United States

Location

GSK Investigational Site

Yuba City, California, United States

Location

GSK Investigational Site

Denver, Colorado, 80230, United States

Location

GSK Investigational Site

Daytona Beach, Florida, 32117, United States

Location

GSK Investigational Site

Edgewater, Florida, 32132, United States

Location

GSK Investigational Site

Fort Lauderdale, Florida, 33308, United States

Location

GSK Investigational Site

Jacksonville, Florida, 32258, United States

Location

GSK Investigational Site

Miami, Florida, 33145, United States

Location

GSK Investigational Site

Miami, Florida, 33150, United States

Location

GSK Investigational Site

Miami, Florida, 33173, United States

Location

GSK Investigational Site

Ocala, Florida, 34471, United States

Location

GSK Investigational Site

Pembroke Pines, Florida, 33028, United States

Location

GSK Investigational Site

Port Charlotte, Florida, 33952, United States

Location

GSK Investigational Site

Savannah, Georgia, 31406, United States

Location

GSK Investigational Site

Evanston, Illinois, 60201, United States

Location

GSK Investigational Site

Gurnee, Illinois, 60031, United States

Location

GSK Investigational Site

Detroit, Michigan, 48236, United States

Location

GSK Investigational Site

Asheville, North Carolina, 28801, United States

Location

GSK Investigational Site

Charlotte, North Carolina, United States

Location

GSK Investigational Site

Wilmington, North Carolina, 28401, United States

Location

GSK Investigational Site

Winston-Salem, North Carolina, 27103, United States

Location

GSK Investigational Site

Columbus, Ohio, 43210, United States

Location

GSK Investigational Site

Oklahoma City, Oklahoma, 73116, United States

Location

GSK Investigational Site

Portland, Oregon, 97210, United States

Location

GSK Investigational Site

Bethlehem, Pennsylvania, 18017, United States

Location

GSK Investigational Site

Erie, Pennsylvania, 16507, United States

Location

GSK Investigational Site

Uniontown, Pennsylvania, 15401, United States

Location

GSK Investigational Site

Arlington, Texas, 76011, United States

Location

GSK Investigational Site

Austin, Texas, 78751, United States

Location

GSK Investigational Site

Corsicana, Texas, 75110, United States

Location

GSK Investigational Site

Greenville, Texas, 75402, United States

Location

GSK Investigational Site

Houston, Texas, 77054, United States

Location

GSK Investigational Site

Houston, Texas, 77099, United States

Location

GSK Investigational Site

San Antonio, Texas, 78229, United States

Location

GSK Investigational Site

Temple, Texas, 76502, United States

Location

GSK Investigational Site

Silverdale, Washington, 98383, United States

Location

GSK Investigational Site

Calgary, Alberta, T2R 0X7, Canada

Location

GSK Investigational Site

Brampton, Ontario, L6T 0G1, Canada

Location

GSK Investigational Site

Greater Sudbury, Ontario, P3E 5J1, Canada

Location

GSK Investigational Site

London, Ontario, N6A 5A5, Canada

Location

GSK Investigational Site

Heidelberg, Baden-Wurttemberg, 69120, Germany

Location

GSK Investigational Site

Aschaffenburg, Bavaria, 63741, Germany

Location

GSK Investigational Site

Lehrte, Lower Saxony, 31275, Germany

Location

GSK Investigational Site

Demmin, Mecklenburg-Vorpommern, 17109, Germany

Location

GSK Investigational Site

Hamburg, 22297, Germany

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

Study Record Dates

• First Submitted: April 19, 2012
• First Posted: April 30, 2012
• Study Start: May 17, 2012
• Primary Completion: May 7, 2013
• Study Completion: May 7, 2013
• Last Updated: November 9, 2017
• Results First Posted: November 9, 2017

Record last verified: 2017-08

Data Sharing

• IPD Sharing: Will share

Locations

DE (5); US (46); CA (4)