Clinical trial NCT02988973: A Study of Intermittent Oral Dosing of ASP1517 in Non-Dialysis Chronic Kidney Disease Patients With Anemia
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Kidney Disease
Keywords: Roxadustat
Anemia
Non-dialysis chronic kidney disease
ASP1517
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
Collaborators: name: FibroGen
First posted: 2016-12-12
Enrollment: 334
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 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.

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

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: Up to Week 24
measure: Number of Participants Who Achieved the Average Hb level of 10.0 to 12.0 g/dL For Weeks 18 to 24
timeFrame: Weeks 18 to 24
measure: Number of participants who achieve the target Hb level at each week
timeFrame: Up to Week 24
measure: Change from baseline in Hb to each post-dosing time point
timeFrame: Baseline and Up to Week 52
measure: Proportion of time points that achieve the target Hb level from Weeks 18 to 24
timeFrame: Up to Week 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: Quality of life assessed by SF-36
timeFrame: Up to Week 52
measure: Quality of life assessed by EQ-5D-5L
timeFrame: Up to Week 52
measure: Quality of life assessed by WPAI:ANS
timeFrame: Up to Week 52
measure: Quality of life assessed by FACT-An
timeFrame: Up to Week 52
measure: Average Hb from weeks 44 to 52
timeFrame: Up to Week 52
measure: Change from baseline in the average Hb from weeks 44 to 52
timeFrame: Baseline and Up to Week 52
measure: Number of Participants Who Achieved the Average Hb level of 10.0 to 12.0 g/dL For Weeks 44 to 52
timeFrame: Weeks 44 to 52
measure: Number of participants who achieve the target Hb level at each week
timeFrame: Up to Week 52
measure: Proportion of time points that achieve the target Hb level from Weeks 44 to 52
timeFrame: Up to Week 52
measure: Average Hematocrit Level
timeFrame: Up to Week 52
measure: Average Reticulocyte Level
timeFrame: Up to Week 52
measure: Average Ferrum Level
timeFrame: Up to Week 52
measure: Average Ferritin Level
timeFrame: Up to Week 52
measure: Average Transferrin Level
timeFrame: Up to Week 52
measure: Average Total Iron Binding Capacity Level
timeFrame: Up to Week 52
measure: Average Soluble Transferrin Receptor Level
timeFrame: Up to Week 52
measure: Average Soluble Transferrin Level
timeFrame: Up to Week 52
measure: Average Reticulocyte Hemoglobin Content Level
timeFrame: Up to Week 52
measure: Number of Occurence of Hospitalizations
timeFrame: Up to Week 52
measure: Duration of Hospitalization
timeFrame: Up to week 52
measure: Number of participants with abnormal Vital signs and/or adverse events related to treatment
timeFrame: Up to Week 52
measure: Safety assessed by body weight
timeFrame: Up to Week 52
measure: Safety assessed by incidence of adverse events
timeFrame: Up to Week 52
measure: Safety assessed by standard 12-lead electrocardiogram
timeFrame: Up to Week 52
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
measure: Number of participants with abnormal Laboratory values and/or adverse events related to treatment
timeFrame: Up to Week 52
measure: Plasma concentration of unchanged ASP1517
timeFrame: Up to Week 24
Other outcomes:
Locations:
city: Kasugai
country: Japan
facility: Site JP00009
state: Aichi
city: Nagoya
country: Japan
facility: Site JP00030
state: Aichi
city: Nagoya
country: Japan
facility: Site JP00051
state: Aichi
city: Toyohashi
country: Japan
facility: Site JP00021
state: Aichi
city: Sakura
country: Japan
facility: Site JP00003
state: Chiba
city: Matsuyama
country: Japan
facility: Site JP00038
state: Ehime
city: Matsuyama
country: Japan
facility: Site JP00044
state: Ehime
city: Kitakyusyu
country: Japan
facility: Site JP00008
state: Fukuoka
city: Kitakyusyu
country: Japan
facility: Site JP00013
state: Fukuoka
city: Kitakyusyu
country: Japan
facility: Site JP00040
state: Fukuoka
city: Kitakyusyu
country: Japan
facility: Site JP00057
state: Fukuoka
city: Kurume
country: Japan
facility: Site JP00042
state: Fukuoka
city: Tajimi
country: Japan
facility: Site JP00041
state: Gifu
city: Maebashi
country: Japan
facility: Site JP00002
state: Gunma
city: Hatsukaichi
country: Japan
facility: Site JP00037
state: Hiroshima
city: Kure
country: Japan
facility: Site JP00050
state: Hiroshima
city: Aasahikawa
country: Japan
facility: Site JP00049
state: Hokkaido
city: Sapporo
country: Japan
facility: Site JP00007
state: Hokkaido
city: Sapporo
country: Japan
facility: Site JP00064
state: Hokkaido
city: Amagasaki
country: Japan
facility: Site JP00022
state: Hyogo
city: Nishinomiya
country: Japan
facility: Site JP00066
state: Hyogo
city: Hitachi
country: Japan
facility: Site JP00052
state: Ibaraki
city: Kasama
country: Japan
facility: Site JP00017
state: Ibaraki
city: Koga
country: Japan
facility: Site JP00028
state: Ibaraki
city: Naka
country: Japan
facility: Site JP00053
state: Ibaraki
city: Sashima-gun
country: Japan
facility: Site JP00023
state: Ibaraki
city: Toride
country: Japan
facility: Site JP00019
state: Ibaraki
city: Tsuchiura
country: Japan
facility: Site JP00046
state: Ibaraki
city: Kanazawa
country: Japan
facility: Site JP00035
state: Ishikawa
city: Morioka
country: Japan
facility: Site JP00031
state: Iwate
city: Fujisawa
country: Japan
facility: Site JP00047
state: Kanagawa
city: Kamakura
country: Japan
facility: Site JP00001
state: Kanagawa
city: Yokohama
country: Japan
facility: Site JP00016
state: Kanagawa
city: Yokohama
country: Japan
facility: Site JP00048
state: Kanagawa
city: Sendai
country: Japan
facility: Site JP00012
state: Miyagi
city: Ueda
country: Japan
facility: Site JP00036
state: Nagano
city: Higashiosaka
country: Japan
facility: Site JP00059
state: Osaka
city: Izumisano
country: Japan
facility: Site JP00005
state: Osaka
city: Sakai
country: Japan
facility: Site JP00011
state: Osaka
city: Yao
country: Japan
facility: Site JP00069
state: Osaka
city: Ageo
country: Japan
facility: Site JP00029
state: Saitama
city: Koshigaya
country: Japan
facility: Site JP00004
state: Saitama
city: Koshigaya
country: Japan
facility: Site JP00020
state: Saitama
city: Adachi-ku
country: Japan
facility: Site JP00025
state: Tokyo
city: Bunkyo-ku
country: Japan
facility: Site JP00043
state: Tokyo
city: Chiyoda-ku
country: Japan
facility: Site JP00063
state: Tokyo
city: Hino
country: Japan
facility: Site JP00067
state: Tokyo
city: Koto-ku
country: Japan
facility: Site JP00015
state: Tokyo
city: Minato-ku
country: Japan
facility: Site JP00024
state: Tokyo
city: Musashino
country: Japan
facility: Site JP00006
state: Tokyo
city: Ota-ku
country: Japan
facility: Site JP00060
state: Tokyo
city: Tachikawa
country: Japan
facility: Site JP00062
state: Tokyo
city: Fukui
country: Japan
facility: Site JP00014
city: Fukuoka
country: Japan
facility: Site JP00033
city: Fukuoka
country: Japan
facility: Site JP00065
city: Hiroshima
country: Japan
facility: Site JP00032
city: Hiroshima
country: Japan
facility: Site JP00039
city: Kyoto
country: Japan
facility: Site JP00045
city: Nagano
country: Japan
facility: Site JP00018
city: Nagano
country: Japan
facility: Site JP00068
city: Niigata
country: Japan
facility: Site JP00026
city: Oita
country: Japan
facility: Site JP00034
city: Okayama
country: Japan
facility: Site JP00055
city: Osaka
country: Japan
facility: Site JP00056
city: Osaka
country: Japan
facility: Site JP00061
city: Toyama
country: Japan
facility: Site JP00010
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, 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.