Efficacy and Safety Study of GSK1278863 in Japanese Hemodialysis Subjects With Anemia Associated With Chronic Kidney Disease Who Are Not Taking Erythropoiesis Stimulating Agents

NCT02829320 | Completed Phase 3 Results

• 1 other identifier: 204716
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 17

Brief Summary

This 24-week, Phase 3, open-label, non-comparative, multicentre study aims to evaluate the efficacy and safety of GSK1278863 in Japanese hemodialysis (HD) patients with renal anemia not using erythropoiesis-stimulating agents (ESAs). The primary objective is to evaluate the initial response to GSK1278863 measured by hemoglobin (Hgb) levels in HD patients not using ESAs enrolled in this study. The study is designed to evaluate the appropriateness of the starting dose of GSK1278863 and of the GSK1278863 dose adjustment regimen to achieve or maintain the target Hgb levels. This study will consist of a 4-week screening period, a 24-week treatment period (4-week fixed-dose period and a 20-week dose adjustment period), and a 2- to 4-week follow-up period.

Conditions

Anaemia

Keywords

efficacy; hemodialysis (HD); hemoglobin (Hgb); erythropoiesis-stimulating agents (ESAs); GSK1278863

Outcome Measures

Primary Outcomes (2)

• Change From Baseline in Hgb at Week 4

  Blood samples were collected from participants for measurement of Hgb values. The Baseline value was the latest pre-dose assessment. Change from Baseline at Week 4 was calculated by subtracting Baseline value from the post-dose visit value. The analysis was performed on All Treated Subjects Population which comprised of all participants who received at least one dose of GSK1278863.

  Baseline and Week 4

• Number of Participants by Hgb Change From Baseline Category at Week 4

  Blood samples were collected from participants for measurement of Hgb values. The Baseline value was the latest pre-dose assessment. Change from Baseline at Week 4 was calculated by subtracting Baseline value from the post-dose visit value. The change in Hgb at Week 4 was classified into different categories (i.e., \<=-2.0, \>-2.0 to -1.0, \>-1.0 to 0, \>0 to 1.0, \>1.0 to 2.0, and \>2 g/dL), and the number of participants in each category were summarized.

  Baseline and Week 4

Secondary Outcomes (20)

• Hgb Values at the Indicated Time Points

  Up to Week 24

• Change From Baseline in Hgb at the Indicated Time Points

  Baseline and up to Week 24

• Number of Participants Who Had Hgb Level Within the Target Range (10.0-12.0 g/dL)

  Up to Week 24

• Time to Reach the Lower Target Hgb Level (10.0 g/dL)

  Up to Week 24

• Number of Participants Who Had Hgb Level of Less Than 7.5 g/dL

  Up to Week 24

Study Arms (1)

GSK1278863

EXPERIMENTAL

Subjects will receive GSK1278863 once daily orally at a starting dose of 4 milligrams (mg) on Day 1, and continued until the day of Week 4. From Weeks 4 to 24, interruption of treatment or dose adjustments will be made within the maintenance dose range of 1 mg to 24 mg according to the dose adjustment algorithm to achieve and/or maintain Hgb within the target range (10.0 to 12.0 g/dL) based on the Hgb value measured every 4 weeks. Dose changes will be made every 4 weeks. Iron replacement therapy will be given according to the standard starting criteria.

Drug: GSK1278863; Drug: Iron

Interventions

GSK1278863 DRUG

GSK1278863 will be provided as round, standard biconvex, white film coated tablets containing 1 mg, 2 mg, 4 mg or 6 mg of GSK1278863 as active ingredient.

GSK1278863

Iron DRUG

Subjects will receive supplemental iron therapy if ferritin is \<=100 ng/mL and TSAT is \<=20%. The investigator (or subinvestigator) will choose the route of administration and dose of prescription iron.

GSK1278863

Eligibility Criteria

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

You may qualify if:

• Age (at the time of informed consent): \>=20 years
• Dialysis: Patients on hemodialysis (HD) or hemodiafiltration (HDF)
• Use of any erythropoiesis stimulating agent (ESA): Newly started dialysis (Dialysis newly started \<12 weeks before screening): Patients not using ESAs after the start of dialysis; Maintenance dialysis (Dialysis started \>=12 weeks before screening): Patients not using ESAs within 8 weeks before screening (including interruption of ESA therapy)
• Hemoglobin (Hgb): \>=8.0 to \<10.0 g/dL (measured using a point-of-care Hgb measurement device at the study site on Day 1)
• Iron parameter: Ferritin \>100 nanograms (ng)/milliliter (mL) or transferrin saturation (TSAT) \>20% (at screening only)
• Gender (at screening only): Female or male.
• A female subject is eligible to participate if she is not pregnant (as confirmed by a negative serum human chorionic gonadotropin \[hCG\] test for females of reproductive potential \[FRP\] only), not breastfeeding, and at least one of the following conditions applies:
• Females of non-reproductive potential defined as: Pre-menopausal with one of the following and no plans to utilise assisted reproductive techniques (example \[e.g.\], in vitro fertilisation or donor embryo transfer): documented bilateral tubal ligation or salpingectomy; documented hysteroscopic tube occlusion procedure with follow-up confirmation of bilateral tubal occlusion; hysterectomy; documented bilateral oophorectomy
• Post-menopausal defined as females 60 years of age or older or In females \<60 years of age, 12 months of spontaneous amenorrhea (In questionable cases, a blood sample with simultaneous follicle stimulating hormone \[FSH\] and estradiol levels consistent with menopause is confirmatory \[the reference values are provided separately\]). Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the highly effective 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.
• Females of reproductive potential who agree to follow one of the options listed in the "GlaxoSmithKline (GSK) Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential" from 28 days before the first dose of study treatment until completion of the follow-up visit.
• Informed consent: Subjects who can provide written informed consent to the study, involving compliance with the requirements and patient responsibilities stated in the consent form and the protocol.

You may not qualify if:

• CKD related criteria
• Kidney transplant: Planned living kidney transplant during the study period Anemia-related criteria
• Aplasia: History of bone marrow aplasia or pure red cell aplasia
• Other causes of anemia: Pernicious anemia, thalassaemia, sickle cell disease, or myelodysplastic syndrome
• Gastrointestinal bleeding: Evidence of actively bleeding gastric, duodenal, or esophageal ulcer disease or clinically significant gastrointestinal bleeding within 8 weeks before screening or during a period from screening to Day 1.
• Cardiovascular disease-related criteria
• History of myocardial infarction, acute coronary syndrome, stroke or transient ischemic attack: Diagnosed within 8 weeks before screening or during a period from screening to Day 1.
• Heart failure: Class IV heart failure, as defined by the New York Heart Association (NYHA) functional classification system
• Corrected QT interval (QTc) (at screening only): QTc \>500 milliseconds (msec), or QTc \>530 msec in subject with bundle branch block. Note: Corrected QT interval using Bazett's formula (QTcB) (machine-read or manually) will be used.
• Other disease-related criteria
• Liver disease (if any of the following occurs):
• Alanine transaminase (ALT) \>2x upper limit of normal (ULN)
• Bilirubin \>1.5xULN (If bilirubin fractions are measured and direct bilirubin is \<35%, isolated bilirubin \>1.5xULN will be acceptable.)
• Current unstable active liver or biliary disease (generally defined by the onset of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal/gastric varices, persistent jaundice, or cirrhosis). Note: The only exception is squamous cell or basal cell carcinoma of the skin that has been definitively treated \>=8 weeks before screening.
• Malignancy: History of malignancy within the two years prior to screening, known complex kidney cyst \>3 centimeters (cm) (II F, III or IV based on the Bosniak classification) or currently receiving treatment for cancer. Note: The only exception is squamous cell or basal cell carcinoma of the skin that has been definitively treated \>=8 weeks before screening.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (17)

GSK Investigational Site

Aichi, 455-8530, Japan

Location

GSK Investigational Site

Aichi, 457-8511, Japan

Location

GSK Investigational Site

Fukuoka, 802-8555, Japan

Location

GSK Investigational Site

Hokkaido, 065-8611, Japan

Location

GSK Investigational Site

Ibaraki, 300-0028, Japan

Location

GSK Investigational Site

Ibaraki, 302-0022, Japan

Location

GSK Investigational Site

Ibaraki, 306-0433, Japan

Location

GSK Investigational Site

Kagoshima, 891-0105, Japan

Location

GSK Investigational Site

Kumamoto, 861-8520, Japan

Location

GSK Investigational Site

Kyoto, 613-0034, Japan

Location

GSK Investigational Site

Mie, 510-8101, Japan

Location

GSK Investigational Site

Nagano, 392-8510, Japan

Location

GSK Investigational Site

Nagano, 399-8292, Japan

Location

GSK Investigational Site

Osaka, 555-0001, Japan

Location

GSK Investigational Site

Ōita, 870-0844, Japan

Location

GSK Investigational Site

Shiga, 523-0082, Japan

Location

GSK Investigational Site

Yamagata, 990-0834, Japan

Location

Related Publications (1)

• Tsubakihara Y, Akizawa T, Nangaku M, Onoue T, Yonekawa T, Matsushita H, Endo Y, Cobitz A. A 24-Week Anemia Correction Study of Daprodustat in Japanese Dialysis Patients. Ther Apher Dial. 2020 Apr;24(2):108-114. doi: 10.1111/1744-9987.12962. Epub 2019 Aug 13.

  PMID: 31306555 BACKGROUND

MeSH Terms

Conditions

Anemia

Interventions

GSK1278863; Iron

Condition Hierarchy (Ancestors)

Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Metals, Heavy; Elements; Inorganic Chemicals; Transition Elements; Metals

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 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 8, 2016
• First Posted: July 12, 2016
• Study Start: August 8, 2016
• Primary Completion: May 16, 2017
• Study Completion: October 17, 2017
• Last Updated: December 3, 2019
• Results First Posted: July 13, 2018

Record last verified: 2019-11

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

JP (17)