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AnaemiaPhase 3NCT02829320

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

A Phase 3 study testing GSK1278863 and Iron in people with Anaemia, run by GlaxoSmithKline at 17 sites in Japan.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 20 years and older
Conditions the study is for
Anaemia
What is being tested?
GSK1278863 and Iron
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
28 participants
Where
17 sitesJapan
Study dates
8 Aug 2016to 17 Oct 2017
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 20 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
Show all 11Show fewer
  • 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.

Who cannot join

  • 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
Show all 25Show fewer
  • 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.
  • Concomitant medications and other study treatment-related criteria
  • Iron medication: Planned use of any intravenous iron during the screening period or from Day 1 to Week 4.
  • Note:
  • Patients on oral iron may be enrolled if the iron dose regimen is unchanged during the screening period and from Day 1 to Week 4.
  • Patients on anti-hyperphosphatemia medication containing iron (e.g., ferric citrate hydrate) for at least 12 weeks before screening may be enrolled if the medication is continued during the screening and from Day 1 to Week 4.
  • Severe allergic reactions: History of severe allergic or anaphylactic reactions or hypersensitivity to any excipients in the investigational product
  • Drugs and dietary supplements: Current use of prohibited prescription drugs, non-prescription drugs, or dietary supplements or planned use of any of these drugs during the study period (prohibited drugs: strong cytochrome P450 (CYP)2C8 inducers and inhibitors)
  • Exposure to any other investigational product: Use of an investigational product within the past 30 days or five half lives of that investigational product (whichever is longer).
  • Prior treatment with GSK1278863: Prior treatment with GSK1278863 for >30 days General health-related criteria
  • Other conditions: Any other condition, clinical or laboratory abnormality, or examination finding that the investigator considers would put the subject at unacceptable risk, which may affect study compliance or prevent understanding of the aims or investigational procedures or possible consequences of the study.

Trial locations and contacts

17 sites in 1 country.

17 sites in 1 country

Japan17 sites

  • GSK Investigational Site

    Aichi, 455-8530

  • GSK Investigational Site

    Aichi, 457-8511

  • GSK Investigational Site

    Fukuoka, 802-8555

  • GSK Investigational Site

    Hokkaido, 065-8611

  • GSK Investigational Site

    Ibaraki, 300-0028

  • GSK Investigational Site

    Ibaraki, 302-0022

  • GSK Investigational Site

    Ibaraki, 306-0433

  • GSK Investigational Site

    Kagoshima, 891-0105

  • GSK Investigational Site

    Kumamoto, 861-8520

  • GSK Investigational Site

    Kyoto, 613-0034

  • GSK Investigational Site

    Mie, 510-8101

  • GSK Investigational Site

    Nagano, 392-8510

  • GSK Investigational Site

    Nagano, 399-8292

  • GSK Investigational Site

    Ōita, 870-0844

  • GSK Investigational Site

    Osaka, 555-0001

  • GSK Investigational Site

    Shiga, 523-0082

  • GSK Investigational Site

    Yamagata, 990-0834

Other trials in Japan

About this study

Official title: A 24-week, Phase III, Open-label, Non-comparative, Multi-center Study to Evaluate Efficacy and Safety of GSK1278863 in Japanese Hemodialysis Subjects With Anemia Associated With Chronic Kidney Disease Who Are Not Taking Erythropoiesis Stimulating Agents

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
Being tested
GSK1278863, Iron
Keywords
efficacy, hemodialysis (HD), hemoglobin (Hgb), erythropoiesis-stimulating agents (ESAs), GSK1278863
Medical subject headings
Anemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • GSK1278863Drug

    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.

  • IronDrug

    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.

Study groups in NCT02829320
Study groupRoleWhat they receive
GSK1278863ExperimentalSubjects 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.
Receives: Drug: GSK1278863; Drug: Iron

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Baseline and Week 4

  2. 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.

    Measured: Baseline and Week 4

Secondary outcomes (20)

  1. Hgb Values at the Indicated Time Points

    Blood samples were collected from participants for measurement of Hgb values at indicated time points. Hgb was evaluated using Hgb analyzer.

    Measured: Up to Week 24

  2. Change From Baseline in Hgb at the Indicated Time Points

    Blood samples were collected from participants for measurement of Hgb values at indicated time points. Hgb was evaluated using Hgb analyzer. The Baseline value was the latest pre-dose assessment. Change from Baseline at indicated time-points was calculated by subtracting Baseline value from the post-dose visit value.

    Measured: Baseline and up to Week 24

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

    Blood samples were collected from participants for measurement of Hgb values at indicated time points. Hgb was evaluated using Hgb analyzer. The number of participants with Hgb withinthe target range (10.0 to 12.0 g/dL) at each assessment visit was summarized.

    Measured: Up to Week 24

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

    Blood samples were collected from participants for measurement of Hgb values at indicated time points. Hgb was evaluated using Hgb analyzer. Participants who could not reach lower target were regarded as censored. The time (in days) to reach the lower target Hgb level (10.0 g/dL) was summarized using 25th percentile (P25), median, and 75th percentile (P75) by Kaplan-Meier method.

    Measured: Up to Week 24

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

    Blood samples were collected from participants for measurement of Hgb values at indicated time points. Hgb was evaluated using Hgb analyzer. The number of participants who had Hgb level of less than 7.5 g/dL were summarized. On-therapy Hgb values observed in both scheduled and unscheduled visits were included.

    Measured: Up to Week 24

  6. Number of Participants Who Had Hgb Increase of More Than 2 g/dL Over Any 4 Weeks

    Blood samples were collected from participants for measurement of Hgb values at indicated time points. Hgb was evaluated using Hgb analyzer. The number of participants who had Hgb increase of more than 2.0 g/dL over any 4 weeks were summarized. On-therapy Hgb values observed in both scheduled and unscheduled visits were included.

    Measured: Up to Week 24

  7. Number of Participants Who Had Hgb Level of More Than 13.0 g/dL

    Blood samples were collected from participants for measurement of Hgb values at indicated time points. Hgb was evaluated using Hgb analyzer. The number of participants who had Hgb level of more than 13.0 g/dL were summarized. On-therapy Hgb values observed in both scheduled and unscheduled visits were included.

    Measured: Up to Week 24

  8. Number of Episodes of Achieving Hgb Level of More Than 13.0 g/dL

    Blood samples were collected from participants for measurement of Hgb values at indicated time points. Hgb was evaluated using Hgb analyzer. The number of episodes in participants who had Hgb level of more than 13.0 g/dL were summarized. On-therapy Hgb values observed in both scheduled and unscheduled visits were included.

    Measured: Up to Week 24

  9. Area Under the Concentration-time Curve (AUC) From Time Zero to 4 Hours (AUC [0-4]) of GSK1278863

    Blood samples were collected to evaluate AUC (0-4) at 1, 2, 3 and 4 hours post dose at Weeks 12 and 24. Pharmacokinetic (PK) parameters were calculated by standard non-compartmental analysis. PK Population consisted of all participants who received GSK1278863 with the PK samples collected and analyzed. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles). NA indiates data was not available. Geometric coefficient of variation could not be calculated when number of participant was equal to 1.

    Measured: 1, 2, 3 and 4 hours post dose at Weeks 12 and 24

  10. Maximum Observed Concentration (Cmax) of GSK1278863

    Blood samples were collected to evaluate Cmax at 1, 2, 3 and 4 hours post dose at Weeks 12 and 24. PK parameters were calculated by standard non-compartmental analysis. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles). NA indiates data was not available. Geometric coefficient of variation could not be calculated when number of participant was equal to 1.

    Measured: 1, 2, 3 and 4 hours post dose at Weeks 12 and 24

  11. Monthly Average Dose of Intravenous (IV) Iron During the Treatment Period

    Records of on-therapy iron medication were used to calculate average quarterly IV iron dose. Quarter 1 = (Randomization Date - Treatment Start Date at Week 12 - 1 [day]). Quarter 2 = (Treatment Start Date at Week 12 - Study Treatment Stop Date). Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).

    Measured: Up to Week 24

  12. Number of Participants Who Used Iron During the Treatment Period

    The number of participants who used iron (both IV and oral iron) during the treatment period were summarized.

    Measured: Up to Week 24

  13. Change From Baseline in Ferritin

    Blood samples were collected from participants for measurement of serum ferritin at indicated time points. The Baseline value was the latest pre-dose assessment. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.

    Measured: Baseline and up to Week 24

  14. Percent Change From Baseline in TSAT

    Blood samples were collected from participants for measurement of TSAT at indicated time points. The Baseline value was the latest pre-dose assessment. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Percent change from Baseline was calculated as 100*(exponential [mean change on log scale]-1).

    Measured: Baseline and up to Week 24

  15. Percent Change From Baseline in Hepcidin

    Blood samples were collected from participants for measurement of hepcidin at indicated time points. The Baseline value was the latest pre-dose assessment. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Percent change from Baseline was calculated as 100*(exponential [mean change on log scale]-1). If a laboratory value had a non-detectable level reported in the database, where the numeric value was missing, the value was not included in a summary. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).

    Measured: Baseline and up to Week 24

  16. Change From Baseline in Serum Iron

    Blood samples were collected from participants for measurement of serum iron at indicated time points. The Baseline value was the latest pre-dose assessment. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.

    Measured: Baseline and up to Week 24

  17. Change From Baseline in Total Iron Binding Capacity (TIBC)

    Blood samples were collected from participants for measurement of TIBC at indicated time points. The Baseline value was the latest pre-dose assessment. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.

    Measured: Baseline and up to Week 24

  18. Dose Level of GSK1278863 at Indicated Time Points

    Dose adjustment algorithm was used which was based on Hgb values at scheduled visits. Hgb values measured at unscheduled visits were not included. Mean dose during Week 12 to 24 is the average of dose at Weeks 12, 16, and 20.

    Measured: Up to Week 24

  19. Number of Participants With Frequency of Dose Adjustments

    Dose adjustment algorithm was used which was based on Hgb values at scheduled visits. Hgb values measured at unscheduled visits were not included. For dose adjustments frequency, the number of participants were provided by the number of dose adjustments (i.e. zero, one, two, three, four, and five or more).

    Measured: Up to Week 24

  20. Duration of Treatment Interruption Due to Hgb >13 g/dL

    Hgb values were used for making decision of treatment interruption. On-therapy Hgb values observed in both scheduled and unscheduled visits were counted. Participants who have no treatment interruption due to Hgb >13.0 g/dL are not included

    Measured: Up to Week 24

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Jul 2016 (estimated)
  2. Study start8 Aug 2016
  3. Primary completion16 May 2017
  4. Study completion17 Oct 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
28 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02829320
Sponsor's protocol ID
204716
Status last verified
Nov 2019
First submitted
8 Jul 2016
Last updated
3 Dec 2019
Data monitoring committee
No
Individual data sharing
Yes: IPD for this study will be made available via the Clinical Study Data Request site.

Publications

  • 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.

    PubMed 31306555

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing GSK1278863 and Iron in people with Anaemia, run by GlaxoSmithKline at 17 sites in Japan.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 17 sites in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 13 Jul 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline in Hgb at Week 4 (time frame: Baseline and Week 4). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02829320, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Dec 2019.

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