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

• ClinicalTrials.gov Identifier: NCT03439137
• Recruitment Status: Completed
• First Posted: February 20, 2018
• Last Update Posted: October 31, 2019
• Sponsor: Mitsubishi Tanabe Pharma Corporation
• Information provided by (Responsible Party): Mitsubishi Tanabe Pharma Corporation

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Anemia; Hemodialysis Dependent Chronic Kidney Disease	Drug: MT-6548; Drug: Darbepoetin alfa; Drug: MT-6548-matching placebo; Drug: Darbepoetin alfa-matching placebo	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 323 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: February 14, 2018
• Actual Primary Completion Date: December 12, 2018
• Actual Study Completion Date: July 16, 2019

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Mean Hb level of Week 20 and Week 24 [ Time Frame: Up to Week 24 ]

Secondary Outcome Measures :

1. Mean Hb level of Week 48 and Week 52 [ Time Frame: Up to Week 52 ]
2. Hb level at each assessment time point [ Time Frame: Up to Week 52 ]
3. Proportion of subjects with Hb level at each assesment time point within the target range [ Time Frame: Up to Week 52 ]

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

Japan

Research site

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

Sponsors and Collaborators

Mitsubishi Tanabe Pharma Corporation

Investigators

• Study Director: General Manager; Mitsubishi Tanabe Pharma Corporation

More Information

• Responsible Party: Mitsubishi Tanabe Pharma Corporation
• ClinicalTrials.gov Identifier: NCT03439137
• Other Study ID Numbers: MT-6548-J03
• First Posted: February 20, 2018
• Last Update Posted: October 31, 2019
• Last Verified: October 2019

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Kidney Diseases; Renal Insufficiency, Chronic; Anemia; Hematologic Diseases; Urologic Diseases; Renal Insufficiency; Darbepoetin alfa; Hematinics