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

Astellas

Status and phase: Completed; Phase 3

Conditions: Chronic Kidney Disease

Treatments: Drug: DA; Drug: roxadustat

Study type: Interventional

Funder types: Industry

Identifiers

NCT02988973

1517-CL-0310

Details and patient eligibility

About

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).

Full 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.

Enrollment: 334 patients

Sex: All

Ages: 20+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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334 participants in 3 patient groups

rHuEPO or DA to ASP1517

Experimental group

Description:

Participants will receive roxadustat according to the prior randomization treatment, with starting doses of 70mg thrice weekly (TIW) to participants on \<4500 IU/week of rHuEPO or \<20 microgram (μg)/week of darbepoetin alfa (DA) and 100mg TIW to participants on ≥4500 IU/week rHuEPO or ≥ 20 μg/week DA. Participants roxadustat dosage will be adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps will be as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300 mg.

Treatment:

Drug: roxadustat

rHuEPO or DA to DA

Experimental group

Description:

Participants will receive DA according to the prior randomization treatment, with starting doses of 15 μg/2weeks to participants on ≤ 1500 IU/week of rHuEPO or \<11.25 microgram (μg)/week of DA, 30μg/2weeks to participants on \>1500 to \<6000 IU/week of rHuEPO or ≥ 11.25 to \< 22.5 μg/week of DA, 60μg/2weeks to participants on ≥ 6000 IU/week of rHuEPO or ≥ 22.5 to \< 37.5 μg/week of DA, 90μg/2weeks to participants on ≥ 37.5 to \< 52.5 μg/week of DA, 120μg/2weeks to participants on ≥ 52.5 to \< 75 μg/week of DA, 180μg/2weeks to participants on ≥ 75 μg/week of DA. Participant's roxadustat dosage will be adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps will be as follows: 15, 30, 60, 90, 120, and 180 μg.

Treatment:

Drug: DA

Epoetin beta pegol to ASP1517

Experimental group

Description:

Participants will receive roxadustat according to the prior registration treatment, with starting doses of 70mg thrice weekly (TIW) to participants on ≤100 μg/week of Epoetin beta pegol and 100mg TIW to participants on \>100 μg/week of Epoetin beta pegol. Participant's roxadustat dosage will be adjusted every 4 weeks to maintain Hb level within the target range 10.0 to 12.0 g/dL. Dose adjustment steps will be as follows: 20, 40, 50, 70, 100, 150, 200, 250, 300 mg.

Treatment:

Drug: roxadustat