A Study of Intermittent Oral Dosing of ASP1517 in Non-Dialysis Chronic Kidney Disease Patients With Anemia

A Phase 3 Multi-center, Randomized, Open-label, Active-comparator (Darbepoetin Alfa) Conversion Study of Intermittent Oral Dosing of ASP1517 in Non-dialysis Chronic Kidney Disease Patients With Anemia

The objective of this study is to evaluate the efficacy and safety of ASP1517 when converted from recombinant human erythropoietin (rHuEPO) or darbepoetin alfa (DA), compared to DA in the treatment of anemia in non-dialysis chronic kidney disease patients. Another uncontrolled cohort will be included to evaluate the efficacy and safety of ASP1517 in patients converted from epoetin beta pegol (CERA). This study will also assess the safety/efficacy of long term treatment of ASP1517 (52 weeks).

Study Overview

• Status: Completed
• Conditions: Chronic Kidney Disease
• Intervention / Treatment: Drug: roxadustat; Drug: DA

Detailed Description

This study consists of the following three cohorts. Cohort 1; subjects converted from rHuEPO or DA to ASP1517, Cohort 2; subjects converted from rHuEPO or DA to DA, Cohort 3; subjects converted from epoetin beta pegol (CERA) to ASP1517. In Cohort 1 and 3, ASP1517 will be administered orally for 52 weeks. In Cohort 2, DA will be administered subcutaneously for 24 weeks.

• Study Type: Interventional
• Enrollment (Actual): 334
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Fukui, Japan
    • Site JP00014
  • Fukuoka, Japan
    • Site JP00033
  • Fukuoka, Japan
    • Site JP00065
  • Hiroshima, Japan
    • Site JP00032
  • Hiroshima, Japan
    • Site JP00039
  • Kyoto, Japan
    • Site JP00045
  • Nagano, Japan
    • Site JP00018
  • Nagano, Japan
    • Site JP00068
  • Niigata, Japan
    • Site JP00026
  • Oita, Japan
    • Site JP00034
  • Okayama, Japan
    • Site JP00055
  • Osaka, Japan
    • Site JP00056
  • Osaka, Japan
    • Site JP00061
  • Toyama, Japan
    • Site JP00010
  • Aichi
    • Kasugai, Aichi, Japan
      • Site JP00009
    • Nagoya, Aichi, Japan
      • Site JP00030
    • Nagoya, Aichi, Japan
      • Site JP00051
    • Toyohashi, Aichi, Japan
      • Site JP00021
  • Chiba
    • Sakura, Chiba, Japan
      • Site JP00003
  • Ehime
    • Matsuyama, Ehime, Japan
      • Site JP00038
    • Matsuyama, Ehime, Japan
      • Site JP00044
  • Fukuoka
    • Kitakyusyu, Fukuoka, Japan
      • Site JP00008
    • Kitakyusyu, Fukuoka, Japan
      • Site JP00013
    • Kitakyusyu, Fukuoka, Japan
      • Site JP00040
    • Kitakyusyu, Fukuoka, Japan
      • Site JP00057
    • Kurume, Fukuoka, Japan
      • Site JP00042
  • Gifu
    • Tajimi, Gifu, Japan
      • Site JP00041
  • Gunma
    • Maebashi, Gunma, Japan
      • Site JP00002
  • Hiroshima
    • Hatsukaichi, Hiroshima, Japan
      • Site JP00037
    • Kure, Hiroshima, Japan
      • Site JP00050
  • Hokkaido
    • Aasahikawa, Hokkaido, Japan
      • Site JP00049
    • Sapporo, Hokkaido, Japan
      • Site JP00007
    • Sapporo, Hokkaido, Japan
      • Site JP00064
  • Hyogo
    • Amagasaki, Hyogo, Japan
      • Site JP00022
    • Nishinomiya, Hyogo, Japan
      • Site JP00066
  • Ibaraki
    • Hitachi, Ibaraki, Japan
      • Site JP00052
    • Kasama, Ibaraki, Japan
      • Site JP00017
    • Koga, Ibaraki, Japan
      • Site JP00028
    • Naka, Ibaraki, Japan
      • Site JP00053
    • Sashima-gun, Ibaraki, Japan
      • Site JP00023
    • Toride, Ibaraki, Japan
      • Site JP00019
    • Tsuchiura, Ibaraki, Japan
      • Site JP00046
  • Ishikawa
    • Kanazawa, Ishikawa, Japan
      • Site JP00035
  • Iwate
    • Morioka, Iwate, Japan
      • Site JP00031
  • Kanagawa
    • Fujisawa, Kanagawa, Japan
      • Site JP00047
    • Kamakura, Kanagawa, Japan
      • Site JP00001
    • Yokohama, Kanagawa, Japan
      • Site JP00016
    • Yokohama, Kanagawa, Japan
      • Site JP00048
  • Miyagi
    • Sendai, Miyagi, Japan
      • Site JP00012
  • Nagano
    • Ueda, Nagano, Japan
      • Site JP00036
  • Osaka
    • Higashiosaka, Osaka, Japan
      • Site JP00059
    • Izumisano, Osaka, Japan
      • Site JP00005
    • Sakai, Osaka, Japan
      • Site JP00011
    • Yao, Osaka, Japan
      • Site JP00069
  • Saitama
    • Ageo, Saitama, Japan
      • Site JP00029
    • Koshigaya, Saitama, Japan
      • Site JP00004
    • Koshigaya, Saitama, Japan
      • Site JP00020
  • Tokyo
    • Adachi-ku, Tokyo, Japan
      • Site JP00025
    • Bunkyo-ku, Tokyo, Japan
      • Site JP00043
    • Chiyoda-ku, Tokyo, Japan
      • Site JP00063
    • Hino, Tokyo, Japan
      • Site JP00067
    • Koto-ku, Tokyo, Japan
      • Site JP00015
    • Minato-ku, Tokyo, Japan
      • Site JP00024
    • Musashino, Tokyo, Japan
      • Site JP00006
    • Ota-ku, Tokyo, Japan
      • Site JP00060
    • Tachikawa, Tokyo, Japan
      • Site JP00062

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects who were diagnosed with non-dialysis Chronic Kidney Disease and who are considered not to require renal replacement therapy during the study period
• Subjects with renal anemia who have been receiving erythropoiesis stimulating agent (ESA) by subcutaneous injection and whose Hb values are considered stable.
• Mean of the subject's two most recent Hb values before randomization during the Screening Period must be ≥10.0 g/dL and ≤12.0 g/dL
• Either transferrin saturation ≥ 20% or serum ferritin ≥ 100 ng/mL
• Female subject must either:

Be of non-childbearing potential:

• post-menopausal, or
• documented surgically sterile Or, if of childbearing potential,
• Agree not to try to become pregnant during the study and for 28 days after the final study drug administration
• And have a negative urine pregnancy test at pre-screening

• And, if heterosexually active, agree to consistently use two forms of highly effective birth control* (at least one of which must be a barrier method) starting at pre-screening and throughout the study period and continued for 28 days after the final study drug administration.

  • Female subject must agree not to breastfeed starting at pre-screening and throughout the study period, and continued for 28 days after the final study drug administration.
  • Female subject must not donate ova starting at pre-screening and throughout the study period, and continued for 28 days after the final study drug administration.
  • Male subject and their female spouse/partners who are of childbearing potential must be using two forms of highly effective birth control (at least one of which must be a barrier method) starting at pre-screening and continue throughout the study period, and for 12 weeks after the final study drug administration
  • Male subject must not donate sperm starting at pre-screening and throughout the study period and, for 12 weeks after the final study drug administration

Exclusion Criteria:

• Concurrent retinal neovascular lesion untreated or macular edema untreated, and patients with any condition that significantly compromises the ability to visualize the retina
• Concurrent autoimmune disease with inflammation that could impact erythropoiesis
• History of gastric/intestinal resection considered influential on the absorption of drugs in the gastrointestinal tract (excluding resection of gastric or colon polyps) or concurrent gastro-paresis
• Uncontrolled hypertension
• Concurrent congestive heart failure (NYHA Class III or higher)
• History of hospitalization for treatment of stroke, myocardial infarction, or pulmonary embolism within 12 weeks before the pre-screening assessment
• Positive for hepatitis B surface antigen (HBsAg) or anti-hepatitis C virus (HCV) antibody at the pre-screening assessment, or positive for human immunodeficiency virus (HIV) in a past test
• Concurrent other form of anemia than renal anemia
• History of pure red cell aplasia
• Having received treatment with protein anabolic hormone, testosterone enanthate, or mepitiostane within 6 weeks before the pre-screening assessment
• Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), or total bilirubin that is greater than the criteria, or previous or concurrent another serious liver disease at pre-screening assessment
• Previous or current malignant tumor (no recurrence for at least 5 years is eligible.)
• Having undergone red blood transfusion and/or a surgical procedure consider to promote anemia and/or ophthalmological surgery within 4 weeks before the pre-screening assessment
• Having undergone a kidney transplantation
• History of serious drug allergy including anaphylactic shock
• Having a previous history of treatment with ASP1517 or participation in this study
• Participation in another clinical study or post-marketing clinical study (including that of a medical device) within 12 weeks before informed consent acquisition

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: rHuEPO or DA to ASP1517; Participants will receive roxadustat according to the prior randomization treatment, with starting doses of 70mg thrice weekly (TIW) to participants on <4500 IU/week of rHuEPO or <20 microgram (μg)/week of darbepoetin alfa (DA) and 100mg TIW to participants on ≥4500 IU/week rHuEPO or ≥ 20 μg/week DA. Participants roxadustat dosage will be adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps will be as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300 mg.	Drug: roxadustat; Oral administration; Other Names: ASP1517
Experimental: rHuEPO or DA to DA; Participants will receive DA according to the prior randomization treatment, with starting doses of 15 μg/2weeks to participants on ≤ 1500 IU/week of rHuEPO or <11.25 microgram (μg)/week of DA, 30μg/2weeks to participants on >1500 to <6000 IU/week of rHuEPO or ≥ 11.25 to < 22.5 μg/week of DA, 60μg/2weeks to participants on ≥ 6000 IU/week of rHuEPO or ≥ 22.5 to < 37.5 μg/week of DA, 90μg/2weeks to participants on ≥ 37.5 to < 52.5 μg/week of DA, 120μg/2weeks to participants on ≥ 52.5 to < 75 μg/week of DA, 180μg/2weeks to participants on ≥ 75 μg/week of DA. Participant's roxadustat dosage will be adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps will be as follows: 15, 30, 60, 90, 120, and 180 μg.	Drug: DA; Subcutaneous administration
Experimental: Epoetin beta pegol to ASP1517; Participants will receive roxadustat according to the prior registration treatment, with starting doses of 70mg thrice weekly (TIW) to participants on ≤100 μg/week of Epoetin beta pegol and 100mg TIW to participants on >100 μg/week of Epoetin beta pegol. Participant's roxadustat dosage will be adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps will be as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300 mg.	Drug: roxadustat; Oral administration; Other Names: ASP1517

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in the average Hemoglobin (Hb)	Baseline and Weeks 18 to 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma concentration of unchanged ASP1517		Up to Week 24
Rate of rise in Hb levels (g/dL/week) from week 0 to at the earliest date of week 4, time of discontinuation, or time of dose adjustment		Up to Week 4
Safety assessed by ophthalmological examination: visual acuity		Up to Week 24
Change from baseline in Hb to each post-dosing time point		Baseline and Up to Week 52
Quality of life assessed by SF-36	SF-36: Medical Outcomes Study 36-Item Short-Form Health Survey	Up to Week 52
Quality of life assessed by FACT-An	FACT-An: Functional Assessment of Cancer Therapy-Anemia	Up to Week 52
Safety assessed by incidence of adverse events		Up to Week 52
Safety assessed by standard 12-lead electrocardiogram		Up to Week 52
Number of participants with abnormal Laboratory values and/or adverse events related to treatment		Up to Week 52
Average Hb from Week 18 to Week 24		Up to Week 24
Number of Participants Who Achieved the Average Hb level of 10.0 to 12.0 g/dL For Weeks 18 to 24		Weeks 18 to 24
Number of participants who achieve the target Hb level at each week		Up to Week 24
Proportion of time points that achieve the target Hb level from Weeks 18 to 24		Up to Week 24
Quality of life assessed by EQ-5D-5L	EQ-5D: EuroQol 5 Dimension 5 Levels	Up to Week 52
Quality of life assessed by WPAI:ANS	WPAI:ANS: Work Productivity and Activity Impairment Questionnaire: Anaemic Symptoms	Up to Week 52
Average Hb from weeks 44 to 52		Up to Week 52
Change from baseline in the average Hb from weeks 44 to 52		Baseline and Up to Week 52
Number of Participants Who Achieved the Average Hb level of 10.0 to 12.0 g/dL For Weeks 44 to 52		Weeks 44 to 52
Number of participants who achieve the target Hb level at each week		Up to Week 52
Proportion of time points that achieve the target Hb level from Weeks 44 to 52		Up to Week 52
Average Hematocrit Level		Up to Week 52
Average Reticulocyte Level		Up to Week 52
Average Ferrum Level		Up to Week 52
Average Ferritin Level		Up to Week 52
Average Transferrin Level		Up to Week 52
Average Total Iron Binding Capacity Level		Up to Week 52
Average Soluble Transferrin Receptor Level		Up to Week 52
Average Soluble Transferrin Level		Up to Week 52
Average Reticulocyte Hemoglobin Content Level		Up to Week 52
Number of Occurence of Hospitalizations		Up to Week 52
Duration of Hospitalization		Up to week 52
Number of participants with abnormal Vital signs and/or adverse events related to treatment		Up to Week 52
Safety assessed by body weight		Up to Week 52
Safety assessed by ophthalmological examination: Fundoscopy		Up to Week 24
Safety assessed by ophthalmological examination: optical coherence tomography		Up to Week 24

Collaborators and Investigators

• Sponsor: Astellas Pharma Inc
• Collaborators: FibroGen

Publications and helpful links

General Publications

• 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.
• Akizawa T, Tanaka-Amino K, Otsuka T, Yamaguchi Y. Factors Affecting Doses of Roxadustat Versus Darbepoetin Alfa for Anemia in Nondialysis Patients. Am J Nephrol. 2021;52(9):702-713. doi: 10.1159/000519043. Epub 2021 Oct 8.

Helpful Links

• Link to results on the Astellas Clinical Study.

Study record dates

Study Major Dates

• Study Start (Actual): January 12, 2017
• Primary Completion (Actual): September 13, 2019
• Study Completion (Actual): March 26, 2020

Study Registration Dates

• First Submitted: December 8, 2016
• First Submitted That Met QC Criteria: December 8, 2016
• First Posted (Estimate): December 12, 2016

Study Record Updates

• Last Update Posted (Actual): September 30, 2022
• Last Update Submitted That Met QC Criteria: September 28, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: Anemia; Roxadustat; ASP1517; Non-dialysis chronic kidney disease
• Additional Relevant MeSH Terms: Urologic Diseases; Hematologic Diseases; Renal Insufficiency; Kidney Diseases; Renal Insufficiency, Chronic; Anemia
• Other Study ID Numbers: 1517-CL-0310

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Access to anonymized individual participant level data will not be provided for this trial as it meets one or more of the exceptions described on www.clinicalstudydatarequest.com under "Sponsor Specific Details for Astellas."

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No