A Study of Intermittent Oral Dosing of ASP1517 in Non-Dialysis Chronic Kidney Disease Patients With Anemia

Chronic Kidney Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02988973
• Other study ID #: 1517-CL-0310
• Status: Completed
• Phase: Phase 3
• Start date: January 12, 2017
• Est. completion date: March 26, 2020

Study information

• Verified date: September 2022
• Source: Astellas Pharma Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 334
• Est. completion date: March 26, 2020
• Est. primary completion date: September 13, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Anemia
• Chronic Kidney Disease
• Kidney Diseases
• Renal Insufficiency, Chronic

Intervention

Drug:
• roxadustat
Oral administration
• DA
Subcutaneous administration

Locations

Country	Name	City	State
Japan	Site JP00049	Aasahikawa	Hokkaido
Japan	Site JP00025	Adachi-ku	Tokyo
Japan	Site JP00029	Ageo	Saitama
Japan	Site JP00022	Amagasaki	Hyogo
Japan	Site JP00043	Bunkyo-ku	Tokyo
Japan	Site JP00063	Chiyoda-ku	Tokyo
Japan	Site JP00047	Fujisawa	Kanagawa
Japan	Site JP00014	Fukui
Japan	Site JP00033	Fukuoka
Japan	Site JP00065	Fukuoka
Japan	Site JP00037	Hatsukaichi	Hiroshima
Japan	Site JP00059	Higashiosaka	Osaka
Japan	Site JP00067	Hino	Tokyo
Japan	Site JP00032	Hiroshima
Japan	Site JP00039	Hiroshima
Japan	Site JP00052	Hitachi	Ibaraki
Japan	Site JP00005	Izumisano	Osaka
Japan	Site JP00001	Kamakura	Kanagawa
Japan	Site JP00035	Kanazawa	Ishikawa
Japan	Site JP00017	Kasama	Ibaraki
Japan	Site JP00009	Kasugai	Aichi
Japan	Site JP00008	Kitakyusyu	Fukuoka
Japan	Site JP00013	Kitakyusyu	Fukuoka
Japan	Site JP00040	Kitakyusyu	Fukuoka
Japan	Site JP00057	Kitakyusyu	Fukuoka
Japan	Site JP00028	Koga	Ibaraki
Japan	Site JP00004	Koshigaya	Saitama
Japan	Site JP00020	Koshigaya	Saitama
Japan	Site JP00015	Koto-ku	Tokyo
Japan	Site JP00050	Kure	Hiroshima
Japan	Site JP00042	Kurume	Fukuoka
Japan	Site JP00045	Kyoto
Japan	Site JP00002	Maebashi	Gunma
Japan	Site JP00038	Matsuyama	Ehime
Japan	Site JP00044	Matsuyama	Ehime
Japan	Site JP00024	Minato-ku	Tokyo
Japan	Site JP00031	Morioka	Iwate
Japan	Site JP00006	Musashino	Tokyo
Japan	Site JP00018	Nagano
Japan	Site JP00068	Nagano
Japan	Site JP00030	Nagoya	Aichi
Japan	Site JP00051	Nagoya	Aichi
Japan	Site JP00053	Naka	Ibaraki
Japan	Site JP00026	Niigata
Japan	Site JP00066	Nishinomiya	Hyogo
Japan	Site JP00034	Oita
Japan	Site JP00055	Okayama
Japan	Site JP00056	Osaka
Japan	Site JP00061	Osaka
Japan	Site JP00060	Ota-ku	Tokyo
Japan	Site JP00011	Sakai	Osaka
Japan	Site JP00003	Sakura	Chiba
Japan	Site JP00007	Sapporo	Hokkaido
Japan	Site JP00064	Sapporo	Hokkaido
Japan	Site JP00023	Sashima-gun	Ibaraki
Japan	Site JP00012	Sendai	Miyagi
Japan	Site JP00062	Tachikawa	Tokyo
Japan	Site JP00041	Tajimi	Gifu
Japan	Site JP00019	Toride	Ibaraki
Japan	Site JP00010	Toyama
Japan	Site JP00021	Toyohashi	Aichi
Japan	Site JP00046	Tsuchiura	Ibaraki
Japan	Site JP00036	Ueda	Nagano
Japan	Site JP00069	Yao	Osaka
Japan	Site JP00016	Yokohama	Kanagawa
Japan	Site JP00048	Yokohama	Kanagawa

Sponsors (2)

Lead Sponsor	Collaborator
Astellas Pharma Inc	FibroGen

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline in the average Hemoglobin (Hb)		Baseline and Weeks 18 to 24
Secondary	Average Hb from Week 18 to Week 24		Up to Week 24
Secondary	Number of Participants Who Achieved the Average Hb level of 10.0 to 12.0 g/dL For Weeks 18 to 24		Weeks 18 to 24
Secondary	Number of participants who achieve the target Hb level at each week		Up to Week 24
Secondary	Change from baseline in Hb to each post-dosing time point		Baseline and Up to Week 52
Secondary	Proportion of time points that achieve the target Hb level from Weeks 18 to 24		Up to Week 24
Secondary	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		Up to Week 4
Secondary	Quality of life assessed by SF-36	SF-36: Medical Outcomes Study 36-Item Short-Form Health Survey	Up to Week 52
Secondary	Quality of life assessed by EQ-5D-5L	EQ-5D: EuroQol 5 Dimension 5 Levels	Up to Week 52
Secondary	Quality of life assessed by WPAI:ANS	WPAI:ANS: Work Productivity and Activity Impairment Questionnaire: Anaemic Symptoms	Up to Week 52
Secondary	Quality of life assessed by FACT-An	FACT-An: Functional Assessment of Cancer Therapy-Anemia	Up to Week 52
Secondary	Average Hb from weeks 44 to 52		Up to Week 52
Secondary	Change from baseline in the average Hb from weeks 44 to 52		Baseline and Up to Week 52
Secondary	Number of Participants Who Achieved the Average Hb level of 10.0 to 12.0 g/dL For Weeks 44 to 52		Weeks 44 to 52
Secondary	Number of participants who achieve the target Hb level at each week		Up to Week 52
Secondary	Proportion of time points that achieve the target Hb level from Weeks 44 to 52		Up to Week 52
Secondary	Average Hematocrit Level		Up to Week 52
Secondary	Average Reticulocyte Level		Up to Week 52
Secondary	Average Ferrum Level		Up to Week 52
Secondary	Average Ferritin Level		Up to Week 52
Secondary	Average Transferrin Level		Up to Week 52
Secondary	Average Total Iron Binding Capacity Level		Up to Week 52
Secondary	Average Soluble Transferrin Receptor Level		Up to Week 52
Secondary	Average Soluble Transferrin Level		Up to Week 52
Secondary	Average Reticulocyte Hemoglobin Content Level		Up to Week 52
Secondary	Number of Occurence of Hospitalizations		Up to Week 52
Secondary	Duration of Hospitalization		Up to week 52
Secondary	Number of participants with abnormal Vital signs and/or adverse events related to treatment		Up to Week 52
Secondary	Safety assessed by body weight		Up to Week 52
Secondary	Safety assessed by incidence of adverse events		Up to Week 52
Secondary	Safety assessed by standard 12-lead electrocardiogram		Up to Week 52
Secondary	Safety assessed by ophthalmological examination: Fundoscopy		Up to Week 24
Secondary	Safety assessed by ophthalmological examination: optical coherence tomography		Up to Week 24
Secondary	Safety assessed by ophthalmological examination: visual acuity		Up to Week 24
Secondary	Number of participants with abnormal Laboratory values and/or adverse events related to treatment		Up to Week 52
Secondary	Plasma concentration of unchanged ASP1517		Up to Week 24

External Links

•   Link to results on the Astellas Clinical Study.