Clinical trial NCT02952092: A Study of Intermittent Oral Dosing of ASP1517 in Hemodialysis Chronic Kidney Disease Patients With Anemia
Official title: A Phase 3, Multi-center, Randomized, 2-arm Parallel, Double-blind, Active-comparator (Darbepoetin Alfa) Conversion Study of Intermittent Oral Dosing of ASP1517 in Hemodialysis Chronic Kidney Disease Patients With Anemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hemodialysis Chronic Kidney Disease Patients With Anemia
Keywords: ASP1517
Renal anemia
Hemodialysis
Roxadustat
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
Collaborators: name: FibroGen
First posted: 2016-11-02
Enrollment: 303
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The objective of this study is to evaluate the safety and efficacy of ASP1517 compared to darbepoetin alfa in hemodialysis chronic kidney disease patients with anemia.


Eligibility criteria: Inclusion Criteria:

* Subjects with renal anemia who have been receiving recombinant human erythropoietin (rHuEPO, two times weekly or three times weekly) or darbepoetin alfa (intravenous treatment) within the doses approved in Japan for more than 8 weeks before the screening assessment
* Mean of the subject's two most recent Hb values before dialysis after the longest dialysis interval during the Screening Period must be ≥10.0 g/dL and ≤12.0 g/dL
* Either transferrin saturation (TSAT) ≥ 20% or serum ferritin ≥ 100 ng/mL during the screening period
* Female subject must either:

Be of non-childbearing potential:

* post-menopausal (defined as at least 1 year without any menses) prior to Screening, 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 pregnancy test at Screening
* And, if heterosexually active, agree to consistently use two forms of highly effective form of birth control (at least one of which must be a barrier method) starting at 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 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 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 form of birth control (at least one of which must be a barrier method) starting at 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 Screening and throughout the study period and, for 12 weeks after the final study drug administration

Exclusion Criteria:

* Concurrent retinal neovascular lesion untreated and macular edema untreated
* 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 screening assessment
* Positive for hepatitis B surface antigen (HBsAg) or anti-hepatitis C virus (HCV) antibody at the 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 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 screening assessment
* Previous or current malignant tumor (no recurrence for at least 5 years is eligible.)
* Having undergone blood transfusion and/or a surgical procedure considered to promote anemia (excluding shunt reconstruction surgery for access to the blood) and/or ophthalmological surgery within 4 weeks before the screening assessment
* Having undergone a kidney transplantation
* Having a previous history of treatment with ASP1517
* History of serious drug allergy including anaphylactic shock
* Participation in another clinical study or post-marketing clinical study (including that of a medical device) within 12 weeks before informed consent acquisition

Primary outcomes:
measure: Change from baseline in the average hemoglobin (Hb)
timeFrame: Baseline and Weeks 18 to 24
Secondary outcomes:
measure: Average Hb from Week 18 to Week 24
timeFrame: Week 18 to 24
measure: Proportion of participants with the target Hb level from Week 18 to Week 24
timeFrame: Week 18 to 24
measure: Proportion of participants with the target Hb level at each week
timeFrame: Up to Week 24
measure: Change from week 0 in Hb levels to each week
timeFrame: Up to Week 24
measure: Proportion of measurement points with the target Hb level from Week 18 to Week 24
timeFrame: Week 18 to 24
measure: 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
timeFrame: Up to Week 4
measure: Average hematocrit level
timeFrame: Up to Week 24
measure: Average reticulocyte level
timeFrame: Up to Week 24
measure: Average iron (Fe) level
timeFrame: Up to Week 24
measure: Average ferritin level
timeFrame: Up to Week 24
measure: Average transferrin level
timeFrame: Up to Week 24
measure: Average total iron binding capacity level
timeFrame: Up to Week 24
measure: Average soluble transferrin receptor level
timeFrame: Up to Week 24
measure: Average transferrin saturation level
timeFrame: Up to Week 24
measure: Average reticulocyte hemoglobin content level
timeFrame: Up to Week 24
measure: Quality of life assessed by SF-36
timeFrame: Up to Week 24
measure: Quality of life assessed by EQ-5D-5L
timeFrame: Up to Week 24
measure: Quality of life assessed by FACT-An
timeFrame: Up to Week 24
measure: Number of hospitalizations
timeFrame: Up to Week 24
measure: Duration of hospitalizations
timeFrame: Up to Week 24
measure: Plasma concentration of unchanged ASP1517
timeFrame: Up to Week 24
measure: Safety assessed by incidence of adverse events
timeFrame: Up to Week 24
measure: Number of participants with abnormal Laboratory values and/or adverse events related to treatment
timeFrame: Up to Week 24
measure: Number of participants with abnormal Vital signs and/or adverse events related to treatment
timeFrame: Up to Week 24
measure: Number of participants with abnormal 12-lead electrocardiogram (ECG) values
timeFrame: Up to Week 24
measure: Safety assessed by ophthalmological examination: fundoscopy
timeFrame: Up to Week 24
measure: Safety assessed by ophthalmological examination: Optical coherence tomography
timeFrame: Up to Week 24
measure: Safety assessed by ophthalmological examination: visual acuity
timeFrame: Up to Week 24
Other outcomes:
Locations:
city: Aichi
country: Japan
facility: Site JP00008
city: Aichi
country: Japan
facility: Site JP00018
city: Aichi
country: Japan
facility: Site JP00020
city: Aichi
country: Japan
facility: Site JP00032
city: Aichi
country: Japan
facility: Site JP00033
city: Aichi
country: Japan
facility: Site JP00040
city: Ehime
country: Japan
facility: Site JP00004
city: Ehime
country: Japan
facility: Site JP00055
city: Fukui
country: Japan
facility: Site JP00009
city: Fukui
country: Japan
facility: Site JP00059
city: Fukuoka
country: Japan
facility: Site JP00014
city: Fukuoka
country: Japan
facility: Site JP00049
city: Fukushima
country: Japan
facility: Site JP00010
city: Fukushima
country: Japan
facility: Site JP00056
city: Fukushima
country: Japan
facility: Site JP00057
city: Gifu
country: Japan
facility: Site JP00030
city: Gifu
country: Japan
facility: Site JP00050
city: Gunma
country: Japan
facility: Site JP00011
city: Gunma
country: Japan
facility: Site JP00026
city: Gunma
country: Japan
facility: Site JP00037
city: Hokkaido
country: Japan
facility: Site JP00003
city: Hokkaido
country: Japan
facility: Site JP00031
city: Hokkaido
country: Japan
facility: Site JP00038
city: Hokkaido
country: Japan
facility: Site JP00048
city: Ibaraki
country: Japan
facility: Site JP00017
city: Ibaraki
country: Japan
facility: Site JP00041
city: Ibaraki
country: Japan
facility: Site JP00042
city: Ibaraki
country: Japan
facility: Site JP00045
city: Ibaraki
country: Japan
facility: Site JP00046
city: Ibaraki
country: Japan
facility: Site JP00047
city: Ibaraki
country: Japan
facility: Site JP00054
city: Ibaraki
country: Japan
facility: Site JP00058
city: Kagoshima
country: Japan
facility: Site JP00043
city: Kanagawa
country: Japan
facility: Site JP00005
city: Kumamoto
country: Japan
facility: Site JP00028
city: Kumamoto
country: Japan
facility: Site JP00029
city: Kyoto
country: Japan
facility: Site JP00006
city: Nagano
country: Japan
facility: Site JP00002
city: Nagano
country: Japan
facility: Site JP00012
city: Nagano
country: Japan
facility: Site JP00027
city: Nagano
country: Japan
facility: Site JP00051
city: Nagasaki
country: Japan
facility: Site JP00013
city: Niigata
country: Japan
facility: Site JP00001
city: Niigata
country: Japan
facility: Site JP00034
city: Okayama
country: Japan
facility: Site JP00036
city: Osaka
country: Japan
facility: Site JP00007
city: Osaka
country: Japan
facility: Site JP00015
city: Saitama
country: Japan
facility: Site JP00016
city: Saitama
country: Japan
facility: Site JP00035
city: Tokushima
country: Japan
facility: Site JP00044
city: Tokyo
country: Japan
facility: Site JP00052
city: Tokyo
country: Japan
facility: Site JP00053
city: Toyama
country: Japan
facility: Site JP00021
city: Toyama
country: Japan
facility: Site JP00022
city: Toyama
country: Japan
facility: Site JP00039
city: Yamagata
country: Japan
facility: Site JP00024
city: Yamaguchi
country: Japan
facility: Site JP00025
Study officials:
affiliation: Astellas Pharma Inc
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.
citation: Akizawa T, Iwasaki M, Yamaguchi Y, Majikawa Y, Reusch M. Phase 3, Randomized, Double-Blind, Active-Comparator (Darbepoetin Alfa) Study of Oral Roxadustat in CKD Patients with Anemia on Hemodialysis in Japan. J Am Soc Nephrol. 2020 Jul;31(7):1628-1639. doi: 10.1681/ASN.2019060623. Epub 2020 Jun 3.