Phase III Study of GSK1278863 in Japanese Non-dialysis (ND) and Peritoneal Dialysis (PD) Subjects With Renal Anemia

NCT02791763 | Completed Phase 3 Results

• 1 other identifier: 201753
• Study Type: interventional
• Target: 355
• Locations: 1 country
• Sites: 56

Brief Summary

This is a Phase III, open-label, active-controlled, parallel-group, multi-center study to compare the efficacy and safety of GSK1278863 administered for 52 weeks versus epoetin beta pegol in approximately 286 Japanese ND and 50 PD subjects with renal anemia. The study will consist of three cohorts. Cohort 1 and Cohort 3 will consist of ND subjects (Erythropoiesis-Stimulating Agent \[ESA\] users and ESA non-users) randomized to receive GSK1278863 or epoetin beta pegol in a ratio of 1:1. PD subjects will be enrolled into Cohort 2 and will receive GSK1278863. This study consists of a 4-week screening phase, a 52-week treatment phase (including primary efficacy evaluation period \[Weeks 40 to 52\]), and a 4-week follow-up phase following the treatment phase. The primary objective of this study is to demonstrate non-inferiority of GSK1278863 to epoetin beta pegol based on mean hemoglobin (Hgb) during the primary efficacy evaluation period in ND subjects. ESA non-users from Cohort 1 will be excluded from the primary efficacy analysis. Study results will be used as pivotal study data for an NDA submitted for GSK1278863 for the treatment of renal anemia in Japan.

Conditions

Anaemia

Keywords

Renal Anemia; Japanese; chronic kidney disease; Peritoneal dialysis; GSK1278863; Non-dialysis

Outcome Measures

Primary Outcomes (1)

• Mean Hemoglobin (Hgb) During the Primary Efficacy Evaluation Period (Weeks 40 to 52) in ND Participants

  The mean hemoglobin during the primary efficacy evaluation period in ND participants was estimated by a statistical model using Mixed Model Repeated Measures (MMRM).

  Weeks 40 to 52

Secondary Outcomes (65)

• Number of ND Participants With Mean Hgb in the Target Range (11.0-13.0 g/dL) During the Primary Efficacy Evaluation Period (Weeks 40 to 52)

  Weeks 40 to 52

• Percentage of ND Participants With Mean Hgb in the Target Range (11.0-13.0 g/dL) During the Primary Efficacy Evaluation Period (Weeks 40 to 52)

  Weeks 40 to 52

• Change From Baseline in Hgb at Week 4 in ND Participants

  Baseline (Day 1) and Week 4

• Change From Baseline in Hgb at Week 4 in PD Participants

  Baseline (Day 1) and Week 4

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

  Baseline (Day 1) and Week 4

Study Arms (3)

Daprodustat in ND participants

EXPERIMENTAL

Eligible ND participants will receive oral daprodustat (1, 2, 4, 6, 8, 12, 18 or 24 milligrams \[mg\] as recommended) dose once daily for 52 weeks.

Drug: 1 to 4 mg tablets of GSK1278863; Drug: 6 mg GSK1278863 tablet

Epoetin beta pegol in ND participants

ACTIVE COMPARATOR

Eligible ND participants will receive subcutaneous (SC) epoetin beta pegol (25, 50, 75, 100, 150, 200 or 250 microgram \[µg\] as recommended) dose once every 2 or 4 weeks for 52 weeks.

Drug: Epoetin beta pegol

Daprodustat in PD participants

EXPERIMENTAL

Eligible PD participants will receive oral daprodustat (1, 2, 4, 6, 8, 12, 18 or 24 mg as recommended) dose once daily for 52 weeks.

Drug: 1 to 4 mg tablets of GSK1278863; Drug: 6 mg GSK1278863 tablet

Interventions

1 to 4 mg tablets of GSK1278863 DRUG

7.0 millimeters (mm) round, standard biconvex, white film coated tablets containing 1 mg, 2 mg, or 4 mg of GSK1278863 as active ingredient, to be orally administered once daily.

Daprodustat in ND participants; Daprodustat in PD participants

6 mg GSK1278863 tablet DRUG

9.0 mm round, standard biconvex, white film coated tablets containing 6 mg of GSK1278863 as active ingredient, to be orally administered once daily.

Daprodustat in ND participants; Daprodustat in PD participants

Epoetin beta pegol DRUG

An injectable formulation containing 25 micrograms µg, 50 µg, 75 µg, 100 µg, 150 µg, 200 µg, or 250 µg of epoetin beta pegol per syringe (0.3 mL), supplied as a glass syringe prefilled with epoetin beta pegol solution (clear colorless to pale yellow). Epoetin beta pegol will be subcutaneously administered once every 2 or 4 weeks.

Epoetin beta pegol in ND participants

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 of age
• Screening verification only: Stage of chronic kidney disease (CKD) (ND subjects only): CKD stages 3, 4, and 5 defined by estimated glomerular filtration rate (eGFR) using the Japanese Society of Nephrology-Chronic Kidney Disease Initiatives (JSN-CKDI) formula
• Dialysis:
• Not on dialysis for at least 12 weeks prior to screening (ND subjects)
• On peritoneal dialysis (PD subjects)
• Use of ESA:
• ESA non-users: Have not used ESAs for 8 weeks prior to screening
• ESA users: Have used the same ESA for 8 weeks prior to screening. However, in the ND subjects, the dose of darbepoetin alfa or epoetin beta pegol must be stable (administered once every 4 weeks and up to one-step dose change during 8 weeks prior to screening).
• Hgb: Determined at the site using an Hgb analyzer
• ESA non-users: \>=8.0 g/dL and \<11.0 g/dL
• ESA users: \>=9.0 g/dL and \<=13.0 g/dL
• Iron parameters: Ferritin \>100 nanograms per milliliters (ng/mL) or transferrin saturation (TSAT) \>20% (screening verification only)
• Gender (screening verification only): Female or male. Females: Not pregnant \[demonstrated to be negative for human chorionic gonadotropin (hCG) in urine or serum\], not breast-feeding, and meet at least one of the following:
• Females of non-childbearing potential are defined as follows:
• Pre-menopausal with at least one of the following and no plans to utilize assisted reproductive techniques (e.g., in vitro fertilization or donor embryo transfer):

You may not qualify if:

• Chronic kidney disease (CKD)-related criteria
• Dialysis
• Cohort 1 and Cohort 3: Start or plan to initiate dialysis during the study
• Cohort 2: Plan to stop peritoneal dialysis or start hemodialysis during the study
• Kidney transplant: Planned living-related kidney transplant during the study Anemia-related criteria
• Aplasia: History of bone-marrow hypoplasia or pure red cell aplasia
• Other causes of anemia: pernicious anemia, thalassemia, sickle cell anemia, or myelodysplastic syndromes
• Gastrointestinal (GI) bleeding: Evidence of actively bleeding gastric, duodenal, or esophageal ulcer disease OR clinically significant GI bleeding within 8 weeks prior to screening or during a period from screening to Day 1.
• Cardiovascular disease-related criteria
• Myocardial infarction, acute coronary syndrome, stroke, or transient ischemic attack: Diagnosed within 8 weeks prior to 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
• QT interval corrected for heart rate (QTc) (screening verification only): QTc \>500 milliseconds (msec) or QTc \>530 msec in subjects with bundle branch block Note: QT interval corrected using the Bazett's formula (QTcB) will be used, and Electrocardiogram (ECG) can be mechanically or manually read.
• Other disease-related criteria
• Liver disease (if any of the following occurs):
• (Screening verification only) Alanine transaminase (ALT) \>2 times upper limit of normal (ULN)

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (56)

GSK Investigational Site

Aichi, 453-8566, Japan

Location

GSK Investigational Site

Aichi, 455-8530, Japan

Location

GSK Investigational Site

Aichi, 457-8511, Japan

Location

GSK Investigational Site

Aichi, 486-8510, Japan

Location

GSK Investigational Site

Chiba, 260-8712, Japan

Location

GSK Investigational Site

Chiba, 278-0004, Japan

Location

GSK Investigational Site

Ehime, 790-0024, Japan

Location

GSK Investigational Site

Fukui, 910-8526, Japan

Location

GSK Investigational Site

Fukuoka, 802-8555, Japan

Location

GSK Investigational Site

Fukuoka, 820-8505, Japan

Location

GSK Investigational Site

Fukushima, 963-8052, Japan

Location

GSK Investigational Site

Gifu, 500-8523, Japan

Location

GSK Investigational Site

Gifu, 500-8717, Japan

Location

GSK Investigational Site

Hiroshima, 720-0838, Japan

Location

GSK Investigational Site

Hokkaido, 007-0803, Japan

Location

GSK Investigational Site

Hokkaido, 060-0033, Japan

Location

GSK Investigational Site

Hokkaido, 065-8611, Japan

Location

GSK Investigational Site

Hokkaido, 073-0022, Japan

Location

GSK Investigational Site

Hokkaido, 073-0196, Japan

Location

GSK Investigational Site

Ibaraki, 302-0022, Japan

Location

GSK Investigational Site

Ibaraki, 306-0433, Japan

Location

GSK Investigational Site

Ibaraki, 310-0015, Japan

Location

GSK Investigational Site

Ishikawa, 920-0353, Japan

Location

GSK Investigational Site

Ishikawa, 920-8530, Japan

Location

GSK Investigational Site

Kagoshima, 890-0073, Japan

Location

GSK Investigational Site

Kagoshima, 893-0024, Japan

Location

GSK Investigational Site

Kagoshima, 899-5431, Japan

Location

GSK Investigational Site

Kanagawa, 210-0852, Japan

Location

GSK Investigational Site

Kanagawa, 234-8503, Japan

Location

GSK Investigational Site

Kanagawa, 242-0018, Japan

Location

GSK Investigational Site

Kanagawa, 251-8550, Japan

Location

GSK Investigational Site

Kumamoto, 861-8520, Japan

Location

GSK Investigational Site

Kumamoto, 862-8505, Japan

Location

GSK Investigational Site

Kyoto, 604-8845, Japan

Location

GSK Investigational Site

Kyoto, 611-0041, Japan

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GSK Investigational Site

Kyoto, 612-8555, Japan

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GSK Investigational Site

Nagano, 396-8555, Japan

Location

GSK Investigational Site

Nagano, 399-8292, Japan

Location

GSK Investigational Site

Numakunai, 020-0066, Japan

Location

GSK Investigational Site

Osaka, 530-0012, Japan

Location

GSK Investigational Site

Osaka, 530-8480, Japan

Location

GSK Investigational Site

Osaka, 555-0001, Japan

Location

GSK Investigational Site

Osaka, 558-8558, Japan

Location

GSK Investigational Site

Osaka, 586-8521, Japan

Location

GSK Investigational Site

Osaka, 591-8025, Japan

Location

GSK Investigational Site

Ōita, 874-0011, Japan

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GSK Investigational Site

Saitama, 330-8553, Japan

Location

GSK Investigational Site

Saitama, 335-0023, Japan

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GSK Investigational Site

Shiga, 523-0082, Japan

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GSK Investigational Site

Shizuoka, 425-8505, Japan

Location

GSK Investigational Site

Tokushima, 770-0011, Japan

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GSK Investigational Site

Tokyo, 141-8625, Japan

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GSK Investigational Site

Tottori, 683-0002, Japan

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GSK Investigational Site

Toyama, 932-8503, Japan

Location

GSK Investigational Site

Toyama, 937-0042, Japan

Location

GSK Investigational Site

Toyama, 938-8502, Japan

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

• Nangaku M, Hamano T, Akizawa T, Tsubakihara Y, Nagai R, Okuda N, Kurata K, Nagakubo T, Jones NP, Endo Y, Cobitz AR. Daprodustat Compared with Epoetin Beta Pegol for Anemia in Japanese Patients Not on Dialysis: A 52-Week Randomized Open-Label Phase 3 Trial. Am J Nephrol. 2021;52(1):26-35. doi: 10.1159/000513103. Epub 2021 Feb 9.

  PMID: 33561857 DERIVED

MeSH Terms

Conditions

Anemia; Renal Insufficiency, Chronic

Interventions

GSK1278863; continuous erythropoietin receptor activator

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

Limitations and Caveats

A participant in ND daprodustat/ND epoetin beta pegol/PD daprodustat had data entry error with dose level. This had an impact on outcomes of dose level and number of dose adjustment.

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: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 2, 2016
• First Posted: June 7, 2016
• Study Start: June 6, 2016
• Primary Completion: October 26, 2018
• Study Completion: October 26, 2018
• Last Updated: May 18, 2021
• Results First Posted: November 13, 2019

Record last verified: 2021-04

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 (copy the URL below to your browser)
• 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 (56)