Efficacy and Safety Study to Evaluate MT-6548 in Non-dialysis Subjects With Anemia Associated With Chronic Kidney Disease in Japan

A Phase III, Open-label, Confirmatory Study of MT-6548 Compared to Darbepoetin Alfa in Non-dialysis Subjects With Anemia Associated With Chronic Kidney Disease in Japan

For Non-dialysis subjects 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.

For subjects not currently receiving ESAs, evaluate Hb correction and maintenance effect of MT-6548 and for subjects currently receiving ESAs, evaluate Hb conversion and maintenance effect of MT-6548

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 304
• 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
  • Kagoshima, Japan
    • Research Site
  • Kanagawa, Japan
    • Research Site
  • Kochi, Japan
    • Research Site
  • Kumamoto, Japan
    • Research Site
  • Kyoto, Japan
    • Research Site
  • Miyagi, Japan
    • Research Site
  • Nagano, Japan
    • Research Site
  • Nagasaki, Japan
    • Research Site
  • Nara, Japan
    • Research Site
  • Niigata, Japan
    • Research Site
  • Oita, Japan
    • Research Site
  • Okayama, Japan
    • Research Site
  • Okinawa, Japan
    • Research Site
  • Osaka, Japan
    • Research Site
  • Saga, Japan
    • Research Site
  • Saitama, Japan
    • Research Site
  • Shiga, Japan
    • Research Site
  • Shizuoka, Japan
    • Research Site
  • Tokyo, Japan
    • Research Site
  • Toyama, Japan
    • Research Site
  • Yamanashi, 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
• eGFR < 60 mL/min/1.73m^2 during the screening period
• Not receiving dialysis for 8 weeks prior to the screening period, and not expected to start dialysis during the treatment period
• Correction group: Not being treated with ESAs for the recent 8 weeks prior to the screening period
• Conversion group: 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. Correction group: ≥8.0 g/dL and < 11.0 g/dL Conversion group: ≥9.0 g/dL and ≤12.5 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) during 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: None (Open Label)

Number of Arms

2

Arms and Interventions

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

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
Rate of Increase in Hb Level in Correction Group Only	Up to Week 6
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
Time to Reach the Target Hb Range in Correction Group Only	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, Kokado Y, Ueta K, Kaneko G, Tandai T, Kawaguchi Y, Komatsu Y. Phase 3 Randomized Study Comparing Vadadustat with Darbepoetin Alfa for Anemia in Japanese Patients with Nondialysis-Dependent CKD. J Am Soc Nephrol. 2021 Jul;32(7):1779-1790. doi: 10.1681/ASN.2020091311. Epub 2021 Apr 21.

Study record dates

Study Major Dates

• Study Start (Actual): October 30, 2017
• Primary Completion (Actual): January 8, 2019
• Study Completion (Actual): August 9, 2019

Study Registration Dates

• First Submitted: October 30, 2017
• First Submitted That Met QC Criteria: October 30, 2017
• First Posted (Actual): November 1, 2017

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-J01

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