Clinical trial NCT02964936: A Study of Intermittent Oral Dosing of ASP1517 in ESA-untreated Chronic Kidney Disease Patients With Anemia
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Kidney Disease
Keywords: Anemia
Non-dialysis chronic kidney disease
Roxadustat
ASP1517
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
Collaborators: name: FibroGen
First posted: 2016-11-16
Enrollment: 100
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 the safety when ASP1517 is intermittently administered in Erythropoiesis Stimulating Agent (ESA)-untreated non-dialysis chronic kidney disease patients with anemia.


Eligibility criteria: 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

Primary outcomes:
measure: Change from baseline in hemoglobin (Hb) response rate
timeFrame: Baseline and week 24
Secondary outcomes:
measure: Change from baseline in the average Hb from Week 18 to Week 24
timeFrame: Baseline and Weeks 18 to 24
measure: Proportion of participants who achieve the target Hb level at the average of Week 18 to 24
timeFrame: Weeks 18 to 24
measure: 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
timeFrame: Up to Week 4
measure: Proportion of measurement points with the target Hb level
timeFrame: Weeks 18 to 24
measure: Proportion of participants who achieves the target Hb level at each week
timeFrame: Up to Week 24
measure: Proportion of participants who achieves the lower limit of the target Hb level
timeFrame: Up to Week 24
measure: Time to achieve the lower limit of the target Hb level
timeFrame: Up to Week 24
measure: Change from baseline in Hb level to each week
timeFrame: Baseline and 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 participants with abnormal Vital signs and/or adverse events related to treatment
timeFrame: Up to Week 24
measure: Safety assessed by body weight
timeFrame: Up to Week 24
measure: Safety assessed by incidence of adverse events
timeFrame: Up to Week 24
measure: Safety assessed by standard 12-lead electrocardiogram
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: Plasma concentration of unchanged ASP1517
timeFrame: Up to Week 24
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: Number of hospitalizations
timeFrame: Up to Week 24
measure: Duration of hospitalizations
timeFrame: Up to Week 24
Other outcomes:
Locations:
city: Aichi
country: Japan
facility: Site JP00007
city: Aichi
country: Japan
facility: Site JP00018
city: Aichi
country: Japan
facility: Site JP00028
city: Chiba
country: Japan
facility: Site JP00001
city: Ehime
country: Japan
facility: Site JP00035
city: Fukui
country: Japan
facility: Site JP00012
city: Fukuoka
country: Japan
facility: Site JP00011
city: Fukuoka
country: Japan
facility: Site JP00031
city: Hiroshima
country: Japan
facility: Site JP00030
city: Hiroshima
country: Japan
facility: Site JP00034
city: Hiroshima
country: Japan
facility: Site JP00036
city: Hokkaido
country: Japan
facility: Site JP00005
city: Hyogo
country: Japan
facility: Site JP00020
city: Ibaraki
country: Japan
facility: Site JP00015
city: Ibaraki
country: Japan
facility: Site JP00017
city: Ibaraki
country: Japan
facility: Site JP00021
city: Ibaraki
country: Japan
facility: Site JP00025
city: Ibaraki
country: Japan
facility: Site JP00037
city: Ishikawa
country: Japan
facility: Site JP00033
city: Iwate
country: Japan
facility: Site JP00029
city: Kanagawa
country: Japan
facility: Site JP00006
city: Kanagawa
country: Japan
facility: Site JP00014
city: Kanagawa
country: Japan
facility: Site JP00038
city: Miyagi
country: Japan
facility: Site JP00010
city: Nagano
country: Japan
facility: Site JP00016
city: Niigata
country: Japan
facility: Site JP00024
city: Oita
country: Japan
facility: Site JP00032
city: Osaka
country: Japan
facility: Site JP00003
city: Osaka
country: Japan
facility: Site JP00009
city: Osaka
country: Japan
facility: Site JP00026
city: Saitama
country: Japan
facility: Site JP00002
city: Saitama
country: Japan
facility: Site JP00019
city: Saitama
country: Japan
facility: Site JP00027
city: Tokyo
country: Japan
facility: Site JP00004
city: Tokyo
country: Japan
facility: Site JP00013
city: Tokyo
country: Japan
facility: Site JP00022
city: Tokyo
country: Japan
facility: Site JP00023
city: Toyama
country: Japan
facility: Site JP00008
Study officials:
affiliation: Astellas Pharma Inc
name: Medical Director
role: STUDY_DIRECTOR
References: