A Study of Intermittent Oral Dosing of ASP1517 in Peritoneal Dialysis 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 safety and efficacy of ASP1517 in peritoneal dialysis chronic kidney disease patients with anemia.

Official Title
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A Phase 3, Multi-center, Open-label Study of Intermittent Oral Dosing of ASP1517 in Peritoneal Dialysis Chronic Kidney Disease Patients With Anemia

Conditions
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Peritoneal Dialysis Chronic Kidney Disease Patients With Anemia

Intervention / Treatment
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* Drug: roxadustat


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Subjects who have not received Erythropoieses Stimulating Agents (ESAs): Subjects who have been receiving peritoneal dialysis for more than 4 weeks before the screening assessment Subjects who have never received ESAs after starting peritoneal dialysis, or subjects who have not received ESAs within 6 weeks before the screening assessment. 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 (TSAT) ≥ 5% or serum ferritin ≥ 30 ng/mL during the screening period Subjects who have been receiving ESAs: Subjects with renal anemia who have been receiving ESA within the doses approved in Japan for more than 8 weeks after starting peritoneal dialysis, before the screening assessment 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 TSAT ≥ 20% or serum ferritin ≥ 100 ng/mL during the screening period Exclusion Criteria: Subjects who had trouble with continuing peritoneal dialysis due to peritonitis, development of catheter trouble (e.g. tunnel infection) within 4 weeks before the screening assessment 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 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 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 Having received treatment with protein anabolic hormone, testosterone enanthate, or mepitiostane within 6 weeks before the screening assessment Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), total bilirubin, or Alkaline Phosphatase (ALP) that is greater than the criteria below, 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) 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

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 (ESA Untreated)<br>This group includes subjects who have not received Erythropoieses Stimulating Agents (ESAs). Study drug will be dosed three times weekly and dose adjustments will be made during the study. | Drug: roxadustat<br>* Oral<br>* Other names: ASP1517;|
| Experimental: ASP1517 High Dose Group (ESA Untreated)<br>This group includes subjects who have not received ESAs. Study drug will be dosed three times weekly and dose adjustments will be made during the study. | Drug: roxadustat<br>* Oral<br>* Other names: ASP1517;|
| Experimental: ASP1517 ESAs Treated Group<br>This group includes subjects who have received ESAs. The treatment was converted from ESAs to study drug. Study drug will be dosed three times weekly and dose adjustments will be made during the study. | Drug: roxadustat<br>* Oral<br>* Other names: ASP1517;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hemoglobin (Hb) Response Rate from Week 18 to Week 24 | Hb response defined as average Hb within the target range in this outcome | Up to Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hb Response rate | Hb response is defined as reaching target values for Hb and change of Hb from baseline in this outcome. | Up to Week 24 | 
| Average Hb levels from week 18 to week 24 |  | Up to week 24 | 
| Change from baseline in the average Hb levels of week 18 to week 24 |  | Baseline and up to Week 24 | 
| Rate of rise in Hb levels (g/dL/week) |  | Up to Week 4 | 
| Proportion of time points with target Hb levels |  | Up to Week 24 | 
| Proportion of participants who achieve the target Hb level at each week |  | Up to Week 24 | 
| Proportion of participants who achieve 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 at each week |  | Baseline and Up to Week 24 | 
| Efficacy assessed by hematocrit | Hematocrit will be summarized by ASP1517 low dose Erythropoieses Stimulating Agent (ESA) untreated group, ASP1517 high dose ESA untreated group and ASP1517 ESAs treated Group. | Up to Week 24 | 
| Efficacy assessed by reticulocytes/ erythrocytes | Reticulocytes/Erythrocytes will be summarized by ASP1517 low dose ESA untreated group, ASP1517 high dose ESA untreated group and ASP1517 ESAs treated Group. | Up to Week 24 | 
| Efficacy assessed by Iron (Fe) | Fe will be summarized by ASP1517 low dose ESA untreated group, ASP1517 high dose ESA untreated group and ASP1517 ESAs treated Group. | Up to Week 24 | 
| Efficacy assessed by ferritin | Ferritin will be summarized by ASP1517 low dose ESA untreated group, ASP1517 high dose ESA untreated group and ASP1517 ESAs treated Group. | Up to Week 24 | 
| Efficacy assessed by transferrin | Transferrin will be summarized by ASP1517 low dose ESA untreated group, ASP1517 high dose ESA untreated group and ASP1517 ESAs treated Group. | Up to Week 24 | 
| Efficacy assessed by total iron binding capacity | Total iron binding capacity will be summarized by ASP1517 low dose ESA untreated group, ASP1517 high dose ESA untreated group and ASP1517 ESAs treated Group. | Up to Week 24 | 
| Efficacy assessed by soluble transferrin receptor | Soluble transferrin receptor will be summarized by ASP1517 low dose ESA untreated group, ASP1517 high dose ESA untreated group and ASP1517 ESAs treated Group. | Up to Week 24 | 
| Efficacy assessed by transferrin saturation | Transferrin saturation will be summarized by ASP1517 low dose ESA untreated group, ASP1517 high dose ESA untreated group and ASP1517 ESAs treated Group. | Up to Week 24 | 
| Efficacy assessed by reticulocyte hemoglobin content | Reticulocyte hemoglobin content will be summarized by ASP1517 low dose ESA untreated group, ASP1517 high dose ESA untreated group and ASP1517 ESAs treated Group. | Up to Week 24 | 
| Quality of life assessed by SF-36 | SF-36: Medical Outcomes Study 36-Item Short-Form Health Survey | Up to Week 24 | 
| Quality of life assessed by EQ-5D | EQ-5D: EuroQol 5 Dimension | Up to Week 24 | 
| Quality of life assessed by FACT-An | FACT-An: Functional Assessment of Cancer Therapy-Anemia | Up to Week 24 | 
| Occurrence of hospitalizations |  | Up to Week 24 | 
| Safety assessed by incidence of adverse events |  | 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 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Peritoneal dialysis, Roxadustat, Renal anemia, ASP1517