Efficacy and Safety Study to Evaluate MT-6548 in Hemodialysis Subjects Currently Receiving ESAs With Anemia Associated With Chronic Kidney Disease in Japan

A Phase III, Double Blind, Confirmatory Study of MT-6548 Compared to Darbepoetin Alfa in Hemodialysis Subjects With Anemia Associated With Chronic Kidney Disease in Japan

For hemodialysis subjects currently receiving ESAs with anemia associated with chronic kidney disease, demonstrate non-inferiority of MT-6548 compared to darbepoetin alfa using Hb value and evaluate long-term safety of MT-6548.

Study Overview

• Status: Completed
• Conditions: Anemia; Hemodialysis Dependent Chronic Kidney Disease
• Intervention / Treatment: Drug: MT-6548; Drug: Darbepoetin alfa-matching placebo; Drug: Darbepoetin alfa; Drug: MT-6548-matching placebo

• Study Type: Interventional
• Enrollment (Actual): 323
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Aichi, Japan
    • Research Site
  • Chiba, Japan
    • Research Site
  • Fukui, Japan
    • Research Site
  • Fukuoka, Japan
    • Research Site
  • Fukushima, Japan
    • Research Site
  • Gunma, Japan
    • Research Site
  • Hiroshima, Japan
    • Research Site
  • Hokkaido, Japan
    • Research Site
  • Hyogo, Japan
    • Research Site
  • Ibaraki, Japan
    • Research Site
  • Kagawa, Japan
    • Research Site
  • Kagoshima, Japan
    • Research Site
  • Kanagawa, Japan
    • Research Site
  • Kumamoto, Japan
    • Research Site
  • Kyoto, Japan
    • Research Site
  • Miyagi, Japan
    • Research Site
  • Nagano, Japan
    • Research Site
  • Nagasaki, Japan
    • Research Site
  • Oita, Japan
    • Research Site
  • Okayama, Japan
    • Research Site
  • Okinawa, Japan
    • Research Site
  • Osaka, Japan
    • Research Site
  • Saitama, Japan
    • Research Site
  • Shiga, Japan
    • Research Site
  • Shizuoka, Japan
    • Research Site
  • Tokushma, Japan
    • Research Site
  • Tokyo, Japan
    • Research Site
  • Yamagata, Japan
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosis of CKD
• Receiving hemodialysis or hemodiafiltration 3 times a week for more than 12 weeks prior to the screening period, excluding receiving home dialysis or combination of peritoneal dialysis.
• Being treated with ESAs for the recent 8 weeks prior to the screening period
• Mean of the two screening Hb levels closest in time to the baseline visit is ≥9.5 g/dL and ≤12.0 g/dL
• Fluctuation between the two Hb levels closest in time to the baseline visit during the screening period less than 1.5 g/dL
• Serum ferritin ≥ 100 ng/mL, or TSAT ≥20% during the screening period
• Folate and vitamin B12 ≥ lower limit of normal during the screening period

Exclusion Criteria:

• Anemia due to a main cause other than CKD: sickle cell disease, myelodysplastic syndrome, bone marrow fibrosis, hematologic malignancy, hemolytic anemia, thalassemia, or pure red cell aplasia
• Active bleeding or recent blood loss within 8 weeks prior to the screening period
• RBC transfusion within 8 weeks prior to the screening period
• Received testosterone enanthate or mepitiostane within 8 weeks prior to the screening period
• AST, ALT, or total bilirubin >2.5 x upper limit of normal during the screening period
• Uncontrolled hypertension (diastolic blood pressure >110 mm Hg or systolic blood pressure >180 mm Hg) at the first day of the screening period and Day 1

• Ophthalmic examinations during the screening period correspond to either of the following criteria;

  • No available fundal findings
  • Findings indicating the presence of active fundal disease
• Severe heart failure (New York Heart Association Class IV)
• Cerebrovascular disorder or acute coronary syndrome (hospitalization due to unstable angina or myocardial infarction), requiring hospitalization due to urgent percutaneous intervention for coronary or heart failure within 12 weeks prior to the screening period
• Current or history of malignancy. History of malignancy with no recurrence for the recent 5 years is not an exclusion criterion
• New onset or recurrent event of deep vein thrombosis or pulmonary embolism within 12 weeks prior to the screening period
• Current or history of hemosiderosis or hemochromatosis
• History of prior organ transplantation or scheduled organ transplant, or prior transplantation of hematopoietic stem cell or bone marrow
• Males and females of childbearing potential who are unwilling to use an acceptable method of contraception during the designated period (Males: during the study and 90 days after the last dose, females: during study and 30 days after the last dose)
• Females who are pregnant or breast feeding, or are predicted to be pregnant

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Darbepoetin alfa	Drug: Darbepoetin alfa; Intravenous administration; Drug: MT-6548-matching placebo; Oral tablet
Experimental: MT-6548	Drug: MT-6548; Oral tablet; Other Names: AKB-6548; vadadustat; Drug: Darbepoetin alfa-matching placebo; Intravenous administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Mean Hb Level of Week 20 and Week 24	Up to Week 24

Secondary Outcome Measures

Outcome Measure	Time Frame
Mean Hb Level of Week 48 and Week 52	Up to Week 52
Hb Level at Each Assessment Time Point	Up to Week 52
Percentage of Subjects With Hb Level at Each Assessment Time Point Within the Target Range During the Treatment Period	Up to Week 52

Collaborators and Investigators

• Sponsor: Mitsubishi Tanabe Pharma Corporation
• Investigators: Study Director: General Manager, Mitsubishi Tanabe Pharma Corporation

Publications and helpful links

General Publications

• Natale P, Palmer SC, Jaure A, Hodson EM, Ruospo M, Cooper TE, Hahn D, Saglimbene VM, Craig JC, Strippoli GF. Hypoxia-inducible factor stabilisers for the anaemia of chronic kidney disease. Cochrane Database Syst Rev. 2022 Aug 25;8(8):CD013751. doi: 10.1002/14651858.CD013751.pub2.
• Nangaku M, Kondo K, Ueta K, Kokado Y, Kaneko G, Matsuda H, Kawaguchi Y, Komatsu Y. Efficacy and safety of vadadustat compared with darbepoetin alfa in Japanese anemic patients on hemodialysis: a Phase 3, multicenter, randomized, double-blind study. Nephrol Dial Transplant. 2021 Aug 27;36(9):1731-1741. doi: 10.1093/ndt/gfab055.

Study record dates

Study Major Dates

• Study Start (Actual): February 14, 2018
• Primary Completion (Actual): December 12, 2018
• Study Completion (Actual): July 16, 2019

Study Registration Dates

• First Submitted: February 14, 2018
• First Submitted That Met QC Criteria: February 14, 2018
• First Posted (Actual): February 20, 2018

Study Record Updates

• Last Update Posted (Actual): December 28, 2023
• Last Update Submitted That Met QC Criteria: December 8, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Urologic Diseases; Disease Attributes; Hematologic Diseases; Renal Insufficiency; Chronic Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Renal Insufficiency, Chronic; Anemia; Hematinics; Darbepoetin alfa
• Other Study ID Numbers: MT-6548-J03

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes