A Study to Evaluate Efficacy and Safety of Daprodustat Compared to Darbepoetin Alfa in Japanese Hemodialysis (HD)-Dependent Subjects With Anemia Associated With Chronic Kidney Disease (CKD)

NCT ID: NCT02969655

Last Updated: 2020-11-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 271 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-11-21
• Study Completion Date: 2018-07-02

Brief Summary

Daprodustat is a drug that is currently being developed as a treatment for renal anemia . This study is to evaluate the efficacy and safety of daprodustat following a switch from erythropoiesis-stimulating agent (ESA) in Japanese HD subjects with renal anemia who are currently treated with ESA. The primary objective is to demonstrate non-inferiority of daprodustat to darbepoetin alfa. This study is a 52-week, Phase III, double-blind, active-controlled, parallel-group, multi-center study. The total duration of the study will be approximately 58 weeks including screening and follow-up.

Conditions

Anaemia

Keywords

Safety; Efficacy; Daprodustat; Chronic kidney disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Daprodustat

Subjects will receive oral daprodustat once daily and intravenous (IV) darbepoetin alfa placebo once weekly for 52 weeks

Group Type: EXPERIMENTAL

Daprodustat small

Intervention Type: DRUG

Available as 7.0 millimeter (mm) round, standard biconvex, white film coated tablets containing 1 mg, 2 mg, or 4 mg of daprodustat as active ingredient

Daprodustat large

Intervention Type: DRUG

Available as 9.0 mm round, standard biconvex, white film coated tablets containing 6 mg of daprodustat as active ingredient

Darbepoetin alfa placebo

Intervention Type: DRUG

Available as 0.5 mL plastic PFS for IV injection containing no darbepoetin alfa in a clear and colorless solution.

Darbepoetin alfa

Subjects will receive IV darbepoetin alfa once weekly and oral daprodustat placebo once daily for 52 weeks

Group Type: ACTIVE_COMPARATOR

Daprodustat small placebo

Intervention Type: DRUG

Available as 7.0 mm round, standard biconvex, white film coated tablets containing no daprodustat

Daprodustat large placebo

Intervention Type: DRUG

Available as 9.0 mm round, standard biconvex, white film coated tablets containing no daprodustat

Darbepoetin alfa

Intervention Type: DRUG

Available as 0.5 mL plastic prefilled syringes (PFS) for IV injection each containing 10, 15, 20, 30, 40 or 60 mcg of darbepoetin alfa in a clear and colorless solution.

Interventions

Daprodustat small

Available as 7.0 millimeter (mm) round, standard biconvex, white film coated tablets containing 1 mg, 2 mg, or 4 mg of daprodustat as active ingredient

Intervention Type: DRUG

Daprodustat small placebo

Available as 7.0 mm round, standard biconvex, white film coated tablets containing no daprodustat

Intervention Type: DRUG

Daprodustat large

Available as 9.0 mm round, standard biconvex, white film coated tablets containing 6 mg of daprodustat as active ingredient

Intervention Type: DRUG

Daprodustat large placebo

Available as 9.0 mm round, standard biconvex, white film coated tablets containing no daprodustat

Intervention Type: DRUG

Darbepoetin alfa

Available as 0.5 mL plastic prefilled syringes (PFS) for IV injection each containing 10, 15, 20, 30, 40 or 60 mcg of darbepoetin alfa in a clear and colorless solution.

Intervention Type: DRUG

Darbepoetin alfa placebo

Available as 0.5 mL plastic PFS for IV injection containing no darbepoetin alfa in a clear and colorless solution.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Age (informed consent): >=20 years of age
• Dialysis: On HD or hemodiafiltration (HDF) given three times weekly for at least 12 weeks prior to screening
• ESAs: Use of one and the same ESA for 10 weeks prior to screening
• ESA dose: Darbepoetin alfa 10 to 60 μg per week, epoetin (including biosimilars) <=9000 international units (IU) per week, or epoetin beta pegol <=250 μg per 4 weeks
• Hgb:>=9.5 g/dL and <=12.5 g/dL. Determined at the site using an Hgb analyzer
• Iron parameters: Ferritin >100 nanogram (ng)/millilitre (mL) or transferrin saturation (TSAT) >20 percent (screening verification only)
• Gender (screening verification only): Female or male

Females: Not pregnant [demonstrated to be negative for human chorionic gonadotropin (hCG) in 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 utilise assisted reproductive techniques (e.g., in vitro fertilisation or donor embryo transfer):

• History of bilateral tubal ligation or salpingectomy
• History of hysteroscopic tubal occlusion and postoperatively documented bilateral tubal obstruction
• History of hysterectomy
• History of bilateral oophorectomy Postmenopausal defined as A) females 60 years of age or older or B) In females < 60 years of age, 12 months of spontaneous amenorrhea [in questionable cases a blood sample with postmenopausal follicle stimulating hormone (FSH) and estradiol concentrations is confirmatory (see separately specified reference ranges)]. Females on hormone replacement therapy (HRT) whose menopausal status is in doubt will be required to use one of the most 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 enrolment.

• Females of childbearing potential must agree to comply with one of the contraception methods listed as requirements in "GlaxoSmithKline (GSK) Listing of Most Effective Contraceptive Methods for Females of Childbearing Potential from 28 days prior to the first dose of study medication until the completion of the follow-up visit.
• Informed consent: Written informed consent, including adherence to the requirements and conditions specified in the consent form and the protocol, must be obtained from each subject.

Exclusion Criteria

CKD-related criteria

• 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 10 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 10 weeks prior to screening or during a period from screening to Day 1
• Heart failure: Chronic Class IV heart failure, as defined by the New York Heart Association (NYHA) functional classification system
• Corrected QT (QTc) Interval (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):

• Alanine transaminase (ALT) >2 upper limit of normal (ULN)
• Bilirubin >1.5×ULN (isolated bilirubin >1.5 ULN is acceptable if bilirubin is fractionated and direct bilirubin is <35 percent)
• Current unstable active liver or biliary disease (generally defined by the onset of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal/gastric varices, persistent jaundice, or cirrhosis)
• Malignancy: History of malignancy within 2 years prior to screening, currently receiving treatment for cancer, or complex kidney cyst >3 centimeters (cm) (II F, III or IV based on the Bosniak classification)

Concomitant medication and other study treatment-related criteria

• Iron: Planned use of intravenous iron during the screening phase or during a period from Day 1 to Week 4
• Severe allergic reactions: History of severe allergic or anaphylactic reactions or hypersensitivity to excipients in the investigational product.
• Drugs and supplements: Use or planned use of any prescription or non-prescription drugs or dietary supplements that are prohibited during the study period [prohibited medications: strong inducers and inhibitor of Cytochrome P450 (CYP) 2C8].
• Prior investigational product exposure: Use of an investigational agent within 30 days or five half lives of the investigational agent (whichever is longer)
• Prior treatment with daprodustat: Any prior treatment with daprodustat for a treatment duration of >30 days

General health-related criteria

• Other conditions: Any other condition, clinical or laboratory abnormality, or examination finding that the investigator (or subinvestigator) 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.

• Minimum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Aichi, , Japan

GSK Investigational Site

Aichi, , Japan

GSK Investigational Site

Aichi, , Japan

GSK Investigational Site

Aichi, , Japan

GSK Investigational Site

Aichi, , Japan

GSK Investigational Site

Aichi, , Japan

GSK Investigational Site

Aichi, , Japan

GSK Investigational Site

Chiba, , Japan

GSK Investigational Site

Ehime, , Japan

GSK Investigational Site

Ehime, , Japan

GSK Investigational Site

Fukui, , Japan

GSK Investigational Site

Fukuoka, , Japan

GSK Investigational Site

Fukuoka, , Japan

GSK Investigational Site

Fukuoka, , Japan

GSK Investigational Site

Fukuoka, , Japan

GSK Investigational Site

Fukushima, , Japan

GSK Investigational Site

Fukushima, , Japan

GSK Investigational Site

Gunma, , Japan

GSK Investigational Site

Gunma, , Japan

GSK Investigational Site

Gunma, , Japan

GSK Investigational Site

Hokkaido, , Japan

GSK Investigational Site

Hokkaido, , Japan

GSK Investigational Site

Hokkaido, , Japan

GSK Investigational Site

Hokkaido, , Japan

GSK Investigational Site

Ibaraki, , Japan

GSK Investigational Site

Ibaraki, , Japan

GSK Investigational Site

Ibaraki, , Japan

GSK Investigational Site

Kagawa, , Japan

GSK Investigational Site

Kanagawa, , Japan

GSK Investigational Site

Kanagawa, , Japan

GSK Investigational Site

Kanagawa, , Japan

GSK Investigational Site

Kanagawa, , Japan

GSK Investigational Site

Kyoto, , Japan

GSK Investigational Site

Miyagi, , Japan

GSK Investigational Site

Nagano, , Japan

GSK Investigational Site

Nagano, , Japan

GSK Investigational Site

Nagano, , Japan

GSK Investigational Site

Okayama, , Japan

GSK Investigational Site

Osaka, , Japan

GSK Investigational Site

Osaka, , Japan

GSK Investigational Site

Osaka, , Japan

GSK Investigational Site

Osaka, , Japan

GSK Investigational Site

Saitama, , Japan

GSK Investigational Site

Shizuoka, , Japan

GSK Investigational Site

Tokyo, , Japan

GSK Investigational Site

Tokyo, , Japan

GSK Investigational Site

Toyama, , Japan

GSK Investigational Site

Toyama, , Japan

GSK Investigational Site

Yamagata, , Japan

GSK Investigational Site

Yamaguchi, , Japan

Countries

Japan

References

Akizawa T, Nangaku M, Yonekawa T, Okuda N, Kawamatsu S, Onoue T, Endo Y, Hara K, Cobitz AR. Efficacy and Safety of Daprodustat Compared with Darbepoetin Alfa in Japanese Hemodialysis Patients with Anemia: A Randomized, Double-Blind, Phase 3 Trial. Clin J Am Soc Nephrol. 2020 Aug 7;15(8):1155-1165. doi: 10.2215/CJN.16011219. Epub 2020 Jul 28.

Reference Type: BACKGROUND

PMID: 32723804 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 36005278 (View on PubMed)

Provided Documents

Document Type: Statistical Analysis Plan

View Document

Document Type: Study Protocol

View Document

Other Identifiers

201754

Identifier Type: -

Identifier Source: org_study_id