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

NCT ID: NCT02988973

Last Updated: 2024-10-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 334 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-01-12
• Study Completion Date: 2020-03-26

Brief Summary

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).

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.

Conditions

Chronic Kidney Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

roxadustat

Intervention Type: DRUG

Oral administration

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.

Group Type: EXPERIMENTAL

DA

Intervention Type: DRUG

Subcutaneous administration

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.

Group Type: EXPERIMENTAL

roxadustat

Intervention Type: DRUG

Oral administration

Interventions

roxadustat

Oral administration

Intervention Type: DRUG

DA

Subcutaneous administration

Intervention Type: DRUG

Other Intervention Names

ASP1517

Eligibility Criteria

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

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

Sponsors

FibroGen

INDUSTRY

Sponsor Role: collaborator

Astellas Pharma Inc

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Astellas Pharma Inc

Locations

Site JP00009

Kasugai, Aichi-ken, Japan

Site JP00030

Nagoya, Aichi-ken, Japan

Site JP00051

Nagoya, Aichi-ken, Japan

Site JP00021

Toyohashi, Aichi-ken, Japan

Site JP00003

Sakura, Chiba, Japan

Site JP00038

Matsuyama, Ehime, Japan

Site JP00044

Matsuyama, Ehime, Japan

Site JP00008

Kitakyushu, Fukuoka, Japan

Site JP00013

Kitakyushu, Fukuoka, Japan

Site JP00040

Kitakyushu, Fukuoka, Japan

Site JP00057

Kitakyushu, Fukuoka, Japan

Site JP00042

Kurume, Fukuoka, Japan

Site JP00041

Tajimi, Gifu, Japan

Site JP00002

Maebashi, Gunma, Japan

Site JP00037

Hatsukaichi, Hiroshima, Japan

Site JP00050

Kure, Hiroshima, Japan

Site JP00049

Aasahikawa, Hokkaido, Japan

Site JP00007

Sapporo, Hokkaido, Japan

Site JP00064

Sapporo, Hokkaido, Japan

Site JP00022

Amagasaki, Hyōgo, Japan

Site JP00066

Nishinomiya, Hyōgo, Japan

Site JP00052

Hitachi, Ibaraki, Japan

Site JP00017

Kasama, Ibaraki, Japan

Site JP00028

Koga, Ibaraki, Japan

Site JP00053

Naka, Ibaraki, Japan

Site JP00023

Sashima-gun, Ibaraki, Japan

Site JP00019

Toride, Ibaraki, Japan

Site JP00046

Tsuchiura, Ibaraki, Japan

Site JP00035

Kanazawa, Ishikawa-ken, Japan

Site JP00031

Morioka, Iwate, Japan

Site JP00047

Fujisawa, Kanagawa, Japan

Site JP00001

Kamakura, Kanagawa, Japan

Site JP00016

Yokohama, Kanagawa, Japan

Site JP00048

Yokohama, Kanagawa, Japan

Site JP00012

Sendai, Miyagi, Japan

Site JP00036

Ueda, Nagano, Japan

Site JP00059

Higashiosaka, Osaka, Japan

Site JP00005

Izumisano, Osaka, Japan

Site JP00011

Sakai, Osaka, Japan

Site JP00069

Yao, Osaka, Japan

Site JP00029

Ageo, Saitama, Japan

Site JP00004

Koshigaya, Saitama, Japan

Site JP00020

Koshigaya, Saitama, Japan

Site JP00025

Adachi-ku, Tokyo, Japan

Site JP00043

Bunkyo-ku, Tokyo, Japan

Site JP00063

Chiyoda-ku, Tokyo, Japan

Site JP00067

Hino, Tokyo, Japan

Site JP00015

Koto-ku, Tokyo, Japan

Site JP00024

Minato-ku, Tokyo, Japan

Site JP00006

Musashino, Tokyo, Japan

Site JP00060

Ōta-ku, Tokyo, Japan

Site JP00062

Tachikawa, Tokyo, Japan

Site JP00014

Fukui, , Japan

Site JP00033

Fukuoka, , Japan

Site JP00065

Fukuoka, , Japan

Site JP00032

Hiroshima, , Japan

Site JP00039

Hiroshima, , Japan

Site JP00045

Kyoto, , Japan

Site JP00018

Nagano, , Japan

Site JP00068

Nagano, , Japan

Site JP00026

Niigata, , Japan

Site JP00055

Okayama, , Japan

Site JP00056

Osaka, , Japan

Site JP00061

Osaka, , Japan

Site JP00034

Ōita, , Japan

Site JP00010

Toyama, , Japan

Countries

Japan

References

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)

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.

Reference Type: DERIVED

PMID: 34628408 (View on PubMed)

Related Links

https://astellasclinicalstudyresults.com/hcp/study.aspx?ID=398

Link to results on the Astellas Clinical Study.

Other Identifiers

1517-CL-0310

Identifier Type: -

Identifier Source: org_study_id