Study to Evaluate the Safety, Efficacy and Pharmacokinetics of GSK1278863 in Japanese Hemodialysis-Dependent Subjects With Anemia Associated With Chronic Kidney Disease

NCT02019719 | Completed Phase 2 Results DMC

• 1 other identifier: 116099
• Study Type: interventional
• Target: 97
• Locations: 1 country
• Sites: 21

Brief Summary

This study aims to characterize the relationship between dose of GSK1278863 and hemoglobin (Hgb) response in hemodialysis-dependent (HDD) subjects with anemia associated with chronic kidney disease (CKD). 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. This study will consist of a screening phase of 3-9 weeks, a 4-week treatment phase and a follow-up visit approximately 4 weeks after completing treatment.

Conditions

Anaemia

Keywords

Hemodialysis; GSK1278863; Pharmacokinetics; Erythropoiesis Stimulating Agents; Chronic Kidney Disease; Hemoglobin; Recombinant Erythropoietin; Prolyl Hydroxylase Inhibitor; Anemia

Outcome Measures

Primary Outcomes (1)

• Change From Baseline (CFB) in Hemaglobin (Hgb) at Week 4

  Baseline was defined as the value on Day 1. CFB was calculated by subtracting the baseline value from the post-dose value at Week 4. To model the dose-response relationship a four-parameter Emax model was used. E0 is the expected Hgb change from Baseline for a participant receiving placebo and experiencing the average Hgb Baseline observed in the study. Emax is the expected Hgb change from Baseline for a participant receiving the highest dose above which no further increase in response can be achieved. ED50 is the dose that attains the intermediate response. Gamma is the slope parameter. Minimal Effective Dose (MED) is defined as the smallest dose that achieves a placebo-corrected change of 0.5 g/dL over Week 4. Target dose (TD) is defined as the dose that achieves a placebo-corrected 1.0 g/dL change over Week 4. Maximum Acceptable Dose (MAD) is defined as the dose that achieves a placebo-corrected 2.0 g/dL change over Week 4.

  Baseline (Day 1) and Week 4

Secondary Outcomes (17)

• CFB in Hgb Upto Week 8

  Baseline (Day 1) Upto Week 8

• Number of Participants Who Achieved Hgb Response at Week 4

  Week 4

• Percentage of Participants Who Achieved Hgb Response at Week 4

  Week 4

• Number of Participants Who Reached Pre-defined Hgb Stopping Criteria

  Upto Week 4

• Maximum Observed CFB in Erythropoietin (EPO) Upto Week 4

  Baseline (Day 1) Upto Week 4

Study Arms (5)

GSK1278863 4 milligrams (mg)

EXPERIMENTAL

Subjects will receive GSK1278863 4 mg once daily for 4 weeks

Drug: GSK1278863

GSK1278863 6 mg

EXPERIMENTAL

Subjects will receive GSK1278863 6 mg once daily for 4 weeks

Drug: GSK1278863

GSK1278863 8 mg

EXPERIMENTAL

Subjects will receive GSK1278863 8 mg once daily for 4 weeks

Drug: GSK1278863

GSK1278863 10 mg

EXPERIMENTAL

Subjects will receive GSK1278863 10 mg once daily for 4 weeks

Drug: GSK1278863

Placebo

PLACEBO COMPARATOR

Subjects will receive placebo once daily for 4 weeks

Drug: Placebo

Interventions

GSK1278863 DRUG

GSK1278863 will be supplied as film coated tablets for oral administration containing 1 mg, 2 mg, or 5 mg of GSK1278863.

GSK1278863 10 mg; GSK1278863 4 milligrams (mg); GSK1278863 6 mg; GSK1278863 8 mg

Placebo DRUG

Film coated tablets of GSK1278863 matching placebo for oral administration.

Placebo

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age (Informed concent): Japanese \>=20 years of age
• Gender (Screening 2 verification only): Female and male
• Females: must be of childbearing potential, and must agree to use one of the approved contraception methods from Screening 2 until completion of the Follow-up Visit. OR Of non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrea \[in questionable cases a blood sample with simultaneous follicle stimulating hormone 23.0 - 116.3 million international units (MIU)/millilitre (mL) and estradiol \<= 10 picograms (pg)/mL is confirmatory\]. 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 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 2 until completion of the Follow-up Visit.
• Dialysis frequency: On hemodialysis (HD) three times weekly for at least 8 weeks prior to Screening 2 through Day 1.
• Dialysis adequacy (Screening 2 only): 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%.
• Hemoglobin: Target stable Hgb between 9.5-12.0 g/dL at screening.
• Stable erythropoiesis-stimulating agent (ESA) dose (Screening 2 only): Using the same ESA (epoetins or their biosimilar, or darbepoietin) with total weekly doses that varied by no more than 50% during the 4 weeks prior to Screening 2.
• Iron replacement therapy: Subjects may be on stable maintenance oral or intravenous (IV) (\<100 milligrams \[mg\]/week) iron supplementation. If subjects are on oral or IV iron, then doses must be stable for the 4 weeks prior to Screening 2, and Screening 2 through Week 4.

You may not qualify if:

• Dialysis modality: Planned change from HD to peritoneal dialysis within the study time period.
• Renal transplant: Renal transplant anticipated or scheduled within the study time period.
• High ESA dose (Screening 2 verification only): As defined by an epoetin dose of \>=360 IU/kilograms (kg)/week IV or darbepoetin dose of \>=1.8 micrograms (μg)/kg/week IV within the prior 8 weeks through Screening 2.
• methoxy polyethylene glycol epoetin beta (Screening 2 verification only): Use of methoxy polyethylene glycol epoetin beta within the prior 8 weeks through Screening 2.
• Vitamin B12: At or below the lower limit of the reference range
• Folate: \<2.0 nanograms (ng)/mL (\<4.5 nanomoles \[nmol\]/liters \[L\])
• Iron status: Ferritine \<100 ng/mL (\<100 μg/L) AND Transferrin saturation (TSAT) \<20%
• Myocardial infarction or acute coronary syndrome: Within the 8 weeks prior to Screening 2 through Day 1.
• Stroke or transient ischemic attack: Within the 8 weeks prior to Screening 2 through Day 1.
• Heart failure: Class III/IV heart failure, as defined by the New York Heart Association (NYHA) functional classification system or symptomatic right heart failure diagnosed prior to Screening 2 through Day 1.
• Hypertension: Defined using pre-dialysis vitals of diastolic blood pressure \>100 mmHg or systolic blood pressure \>170 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), except vascular access thrombosis, within the 8 weeks prior to Screening 2 through Day 1
• Eyes: History of proliferative retinopathy requiring treatment within the prior 12 months or macular edema requiring treatment..
• Inflammatory disease: Active chronic inflammatory disease that could impact erythropoiesis (e.g., scleroderma, systemic lupus erythematosis, rheumatoid arthritis, celiac disease) diagnosed prior to Screening 2 through Day 1.
• 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 Screening 2 through Day 1.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (21)

GSK Investigational Site

Aichi, 446-0053, Japan

Location

GSK Investigational Site

Aichi, 446-0065, Japan

Location

GSK Investigational Site

Aichi, 454-0932, Japan

Location

GSK Investigational Site

Aichi, 455-0021, Japan

Location

GSK Investigational Site

Aichi, 465-0025, Japan

Location

GSK Investigational Site

Aichi, 470-1201, Japan

Location

GSK Investigational Site

Chiba, 276-0031, Japan

Location

GSK Investigational Site

Fukuoka, 804-0094, Japan

Location

GSK Investigational Site

Ibaraki, 300-0835, Japan

Location

GSK Investigational Site

Ibaraki, 305-0861, Japan

Location

GSK Investigational Site

Ibaraki, 310-0844, Japan

Location

GSK Investigational Site

Kagawa, 761-8024, Japan

Location

GSK Investigational Site

Kanagawa, 216-0007, Japan

Location

GSK Investigational Site

Miyagi, 981-0911, Japan

Location

GSK Investigational Site

Nagano, 390-0821, Japan

Location

GSK Investigational Site

Nagano, 390-1401, Japan

Location

GSK Investigational Site

Niigata, 950-2038, Japan

Location

GSK Investigational Site

Osaka, 543-0052, Japan

Location

GSK Investigational Site

Osaka, 547-0024, Japan

Location

GSK Investigational Site

Tokyo, 158-0094, Japan

Location

GSK Investigational Site

Toyama, 930-0964, Japan

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

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: October 31, 2013
• First Posted: December 24, 2013
• Study Start: November 5, 2013
• Primary Completion: August 6, 2014
• Study Completion: August 6, 2014
• Last Updated: February 12, 2018
• Results First Posted: February 12, 2018

Record last verified: 2018-02

Data Sharing

• IPD Sharing: Will share

Locations

JP (21)