A Study of Intermittent Oral Dosing of ASP1517 in ESA-untreated Chronic Kidney Disease Patients With Anemia

A Phase 3, Multicenter, Randomized, 2-Arm, Open-label Study of Intermittent Oral Dosing of ASP1517 for the Treatment of Anemia in Erythropoiesis Stimulating Agent-untreated Chronic Kidney Disease Patients Not on Dialysis

The objective of this study is to evaluate the efficacy and the safety when ASP1517 is intermittently administered in Erythropoiesis Stimulating Agent (ESA)-untreated non-dialysis chronic kidney disease patients with anemia.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Aichi, Japan
    • Site JP00018
  • Aichi, Japan
    • Site JP00028
  • Aichi, Japan
    • Site JP00007
  • Chiba, Japan
    • Site JP00001
  • Ehime, Japan
    • Site JP00035
  • Fukui, Japan
    • Site JP00012
  • Fukuoka, Japan
    • Site JP00031
  • Fukuoka, Japan
    • Site JP00011
  • Hiroshima, Japan
    • Site JP00034
  • Hiroshima, Japan
    • Site JP00030
  • Hiroshima, Japan
    • Site JP00036
  • Hokkaido, Japan
    • Site JP00005
  • Hyogo, Japan
    • Site JP00020
  • Ibaraki, Japan
    • Site JP00017
  • Ibaraki, Japan
    • Site JP00015
  • Ibaraki, Japan
    • Site JP00021
  • Ibaraki, Japan
    • Site JP00025
  • Ibaraki, Japan
    • Site JP00037
  • Ishikawa, Japan
    • Site JP00033
  • Iwate, Japan
    • Site JP00029
  • Kanagawa, Japan
    • Site JP00014
  • Kanagawa, Japan
    • Site JP00006
  • Kanagawa, Japan
    • Site JP00038
  • Miyagi, Japan
    • Site JP00010
  • Nagano, Japan
    • Site JP00016
  • Niigata, Japan
    • Site JP00024
  • Oita, Japan
    • Site JP00032
  • Osaka, Japan
    • Site JP00026
  • Osaka, Japan
    • Site JP00009
  • Osaka, Japan
    • Site JP00003
  • Saitama, Japan
    • Site JP00027
  • Saitama, Japan
    • Site JP00002
  • Saitama, Japan
    • Site JP00019
  • Tokyo, Japan
    • Site JP00013
  • Tokyo, Japan
    • Site JP00004
  • Tokyo, Japan
    • Site JP00022
  • Tokyo, Japan
    • Site JP00023
  • Toyama, Japan
    • Site JP00008

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 (CKD) and who are considered not to require renal replacement therapy during the study period
• Mean of the subject's two most recent Hb values before randomization during the Screening Period must be <10.5 g/dL with an absolute difference ≤1.3 g/dL between the two values
• Either transferrin saturation ≥ 5% or serum ferritin ≥ 30 ng/mL
• Female subject must either:

Be of non-childbearing potential:

• post-menopausal prior to pre-screening, or
• documented surgically sterile Or, if of childbearing potential,
• Agree not to try to become pregnant during the study after informed consent acquisition 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 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 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 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 requiring treatment and macular edema requiring treatment
• 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 gastroparesis
• 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
• Having received treatment with ESA, 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 considered to promote anemia 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
• 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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ASP1517 Low dose group; Study drug will be dosed three times weekly for 24 weeks and dose adjustments will be made during the study.	Drug: roxadustat; Oral administration; Other Names: ASP1517
Experimental: ASP1517 High dose group; Study drug will be dosed three times weekly for 24 weeks and dose adjustments will be made during the study.	Drug: roxadustat; Oral administration; Other Names: ASP1517

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in hemoglobin (Hb) response rate	Hb response is defined as reaching target values for Hb.	Baseline and week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to achieve the lower limit of the target Hb level		Up to Week 24
Quality of life assessed by FACT-An	FACT-An: Functional Assessment of Cancer Therapy-Anemia	Up to Week 24
Safety assessed by incidence of adverse events		Up to Week 24
Number of participants with abnormal Vital signs and/or adverse events related to treatment		Up to Week 24
Safety assessed by standard 12-lead electrocardiogram		Up to Week 24
Number of participants with abnormal Laboratory values and/or adverse events related to treatment		Up to Week 24
Plasma concentration of unchanged ASP1517		Up to Week 24
Average hematocrit level		Up to Week 24
Average reticulocyte level		Up to Week 24
Average iron (Fe) level		Up to Week 24
Average ferritin level		Up to Week 24
Average transferrin level		Up to Week 24
Average total iron binding capacity level		Up to Week 24
Average soluble transferrin receptor level		Up to Week 24
Average transferrin saturation level		Up to Week 24
Average reticulocyte hemoglobin content level		Up to Week 24
Number of hospitalizations		Up to Week 24
Duration of hospitalizations		Up to Week 24
Change from baseline in the average Hb from Week 18 to Week 24		Baseline and Weeks 18 to 24
Proportion of participants who achieve the target Hb level at the average of Week 18 to 24	Hb response defined as average Hb within the target range in this outcome	Weeks 18 to 24
Rate of rise in Hb levels (g/dL/week) from week 0 at the earliest date of week 4, time to discontinuation, or time of dose adjustment		Up to Week 4
Proportion of measurement points with the target Hb level		Weeks 18 to 24
Proportion of participants who achieves the target Hb level at each week		Up to Week 24
Proportion of participants who achieves the lower limit of the target Hb level		Up to Week 24
Change from baseline in Hb level to each week		Baseline and Up to Week 24
Quality of life assessed by EQ-5D-5L	EQ-5D: EuroQol 5 Dimension 5 Levels	Up to Week 24
Safety assessed by body weight		Up to Week 24

Collaborators and Investigators

• Sponsor: Astellas Pharma Inc
• Collaborators: FibroGen

Publications and helpful links

Helpful Links

• Link to results on the Astellas Clinical Study Results website.

Study record dates

Study Major Dates

• Study Start (Actual): January 11, 2017
• Primary Completion (Actual): August 15, 2018
• Study Completion (Actual): August 15, 2018

Study Registration Dates

• First Submitted: November 13, 2016
• First Submitted That Met QC Criteria: November 13, 2016
• First Posted (Estimate): November 16, 2016

Study Record Updates

• Last Update Posted (Actual): April 12, 2021
• Last Update Submitted That Met QC Criteria: April 8, 2021
• Last Verified: April 1, 2021

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-0314

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as compounds terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Conditions and exceptions are described under the Sponsor Specific Details for Astellas on www.clinicalstudydatarequest.com.
• IPD Sharing Time Frame: Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data.
• IPD Sharing Access Criteria: Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

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