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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Chronic Kidney Disease

Intervention / Treatment
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* Drug: roxadustat


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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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 |
| --- | --- | --- |
| 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 | 
| Time to achieve 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 | 
| Quality of life assessed by FACT-An | FACT-An: Functional Assessment of Cancer Therapy-Anemia | 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 body weight |  | Up to Week 24 | 
| Safety assessed by incidence of adverse events |  | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Anemia, Non-dialysis chronic kidney disease, Roxadustat, ASP1517