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)

NCT02969655 | Completed Phase 3 Results

• 1 other identifier: 201754
• Study Type: interventional
• Target: 271
• Locations: 1 country
• Sites: 50

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

Outcome Measures

Primary Outcomes (1)

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

  The mean hemoglobin during the Evaluation Period was estimated by a statistical model.

  Weeks 40 to 52

Secondary Outcomes (17)

• Percentage of Participants With Mean Hgb in the Target Range (10.0-12.0 g/dL) During the Primary Efficacy Evaluation Period (Weeks 40 to 52)

  Weeks 40 to 52

• Change From Baseline in Hgb (Hgb Increase Rate) at Week 4

  Baseline and Week 4

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

  Week 4

• Distribution of Daprodustat Dose Level by Visit

  Day 1, Weeks 4,8,12,16,20,24,28,32,36,40,44, and 48)

• Distribution of Darbepoetin Alfa Dose Level by Visit

  Day 1, Weeks 2,4,6,8,10,12,14,16,18,20,22,24,26,28,30,32,34,36,38,40,42,44,46,48, and 50

Study Arms (2)

Daprodustat

EXPERIMENTAL

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

Drug: Daprodustat small; Drug: Daprodustat large; Drug: Darbepoetin alfa placebo

Darbepoetin alfa

ACTIVE COMPARATOR

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

Drug: Daprodustat small placebo; Drug: Daprodustat large placebo; Drug: Darbepoetin alfa

Interventions

Daprodustat small 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

Daprodustat small placebo DRUG

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

Darbepoetin alfa

Daprodustat large DRUG

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

Daprodustat

Daprodustat large placebo DRUG

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

Darbepoetin alfa

Darbepoetin alfa 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.

Darbepoetin alfa

Darbepoetin alfa placebo DRUG

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

Daprodustat

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (50)

GSK Investigational Site

Aichi, 441-8023, Japan

Location

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, 462-0802, Japan

Location

GSK Investigational Site

Aichi, 486-8510, Japan

Location

GSK Investigational Site

Chiba, 276-0031, Japan

Location

GSK Investigational Site

Ehime, 790-0962, Japan

Location

GSK Investigational Site

Ehime, 792-0812, Japan

Location

GSK Investigational Site

Fukui, 918-8503, Japan

Location

GSK Investigational Site

Fukuoka, 804-0094, Japan

Location

GSK Investigational Site

Fukuoka, 811-0120, Japan

Location

GSK Investigational Site

Fukuoka, 811-0213, Japan

Location

GSK Investigational Site

Fukuoka, 818-0083, Japan

Location

GSK Investigational Site

Fukushima, 963-8002, Japan

Location

GSK Investigational Site

Fukushima, 963-8071, Japan

Location

GSK Investigational Site

Gunma, 370-0615, Japan

Location

GSK Investigational Site

Gunma, 372-0817, Japan

Location

GSK Investigational Site

Gunma, 375-0024, Japan

Location

GSK Investigational Site

Hokkaido, 004-0814, Japan

Location

GSK Investigational Site

Hokkaido, 007-0803, Japan

Location

GSK Investigational Site

Hokkaido, 073-0022, Japan

Location

GSK Investigational Site

Hokkaido, 073-0196, Japan

Location

GSK Investigational Site

Ibaraki, 300-0062, Japan

Location

GSK Investigational Site

Ibaraki, 302-0011, Japan

Location

GSK Investigational Site

Ibaraki, 305-0861, Japan

Location

GSK Investigational Site

Kagawa, 761-8024, Japan

Location

GSK Investigational Site

Kanagawa, 224-0032, Japan

Location

GSK Investigational Site

Kanagawa, 227-0046, Japan

Location

GSK Investigational Site

Kanagawa, 234-0054, Japan

Location

GSK Investigational Site

Kanagawa, 235-0045, Japan

Location

GSK Investigational Site

Kyoto, 613-0034, Japan

Location

GSK Investigational Site

Miyagi, 981-0954, Japan

Location

GSK Investigational Site

Nagano, 390-0821, Japan

Location

GSK Investigational Site

Nagano, 390-1401, Japan

Location

GSK Investigational Site

Nagano, 399-8292, Japan

Location

GSK Investigational Site

Okayama, 714-0043, Japan

Location

GSK Investigational Site

Osaka, 543-0052, Japan

Location

GSK Investigational Site

Osaka, 547-0024, Japan

Location

GSK Investigational Site

Osaka, 584-0082, Japan

Location

GSK Investigational Site

Osaka, 594-0076, Japan

Location

GSK Investigational Site

Saitama, 348-0045, Japan

Location

GSK Investigational Site

Shizuoka, 424-0012, Japan

Location

GSK Investigational Site

Tokyo, 158-0094, Japan

Location

GSK Investigational Site

Tokyo, 169-0075, Japan

Location

GSK Investigational Site

Toyama, 930-0065, Japan

Location

GSK Investigational Site

Toyama, 938-8502, Japan

Location

GSK Investigational Site

Yamagata, 990-0834, Japan

Location

GSK Investigational Site

Yamaguchi, 755-0155, Japan

Location

Related Publications (2)

• 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.

  PMID: 32723804 BACKGROUND

• 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

MeSH Terms

Conditions

Anemia; Renal Insufficiency, Chronic

Interventions

Darbepoetin alfa

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

Intervention Hierarchy (Ancestors)

Erythropoietin; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Proteins; Amino Acids, Peptides, and Proteins

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: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 17, 2016
• First Posted: November 21, 2016
• Study Start: November 21, 2016
• Primary Completion: July 2, 2018
• Study Completion: July 2, 2018
• Last Updated: November 27, 2020
• Results First Posted: November 29, 2019

Record last verified: 2020-11

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 (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 (50)