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

NCT ID: NCT03329196

Last Updated: 2023-12-28

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

304 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-10-30

Study Completion Date

2019-08-09

Brief Summary

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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

Detailed Description

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Conditions

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Anemia; Non-dialysis Dependent Chronic Kidney Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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MT-6548

Group Type EXPERIMENTAL

MT-6548

Intervention Type DRUG

Oral tablet

Darbepoetin alfa

Group Type ACTIVE_COMPARATOR

Darbepoetin alfa

Intervention Type DRUG

Subcutaneous

Interventions

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MT-6548

Oral tablet

Intervention Type DRUG

Darbepoetin alfa

Subcutaneous

Intervention Type DRUG

Other Intervention Names

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vadadustat AKB-6548

Eligibility Criteria

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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
Minimum Eligible Age

20 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Mitsubishi Tanabe Pharma Corporation

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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General Manager

Role: STUDY_DIRECTOR

Mitsubishi Tanabe Pharma Corporation

Locations

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Research site

Aichi, , Japan

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Chiba, , Japan

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Fukui, , Japan

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Fukuoka, , Japan

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Fukushima, , Japan

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Gunma, , Japan

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Hiroshima, , Japan

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Hokkaido, , Japan

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Hyōgo, , Japan

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Ibaraki, , Japan

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Kagoshima, , Japan

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Kanagawa, , Japan

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Kochi, , Japan

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Kumamoto, , Japan

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Kyoto, , Japan

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Miyagi, , Japan

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Nagano, , Japan

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Nagasaki, , Japan

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Nara, , Japan

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Niigata, , Japan

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Okayama, , Japan

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Okinawa, , Japan

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Osaka, , Japan

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Ōita, , Japan

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Saga, , Japan

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Saitama, , Japan

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Shiga, , Japan

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Shizuoka, , Japan

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Tokyo, , Japan

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Toyama, , Japan

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Yamanashi, , Japan

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Countries

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Japan

References

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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.

Reference Type RESULT
PMID: 33883252 (View on PubMed)

Nangaku M, Ueta K, Nishimura K, Sasaki K, Hashimoto T. Factors affecting responsiveness of vadadustat in patients with anemia associated with chronic kidney disease: a post-hoc subgroup analysis of Japanese phase 3 randomized studies. Clin Exp Nephrol. 2024 May;28(5):391-403. doi: 10.1007/s10157-023-02432-z. Epub 2024 Mar 26.

Reference Type DERIVED
PMID: 38530490 (View on PubMed)

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.

Reference Type DERIVED
PMID: 36005278 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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MT-6548-J01

Identifier Type: -

Identifier Source: org_study_id