Clinical trial NCT03329196: Efficacy and Safety Study to Evaluate MT-6548 in Non-dialysis Subjects With Anemia Associated With Chronic Kidney Disease in Japan
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Anemia; Non-dialysis Dependent Chronic Kidney Disease
Lead sponsor: Mitsubishi Tanabe Pharma Corporation
Sponsor class: INDUSTRY
First posted: 2017-11-01
Enrollment: 304
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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


Eligibility criteria: 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

Primary outcomes:
measure: Mean Hb Level of Week 20 and Week 24
timeFrame: Up to Week 24
Secondary outcomes:
measure: Mean Hb Level of Week 48 and Week 52
timeFrame: Up to Week 52
measure: Hb Level at Each Assessment Time Point
timeFrame: Up to Week 52
measure: Percentage of Subjects With Hb Level at Each Assessment Time Point Within the Target Range During the Treatment Period
timeFrame: Up to Week 52
measure: Time to Reach the Target Hb Range in Correction Group Only
timeFrame: Up to Week 52
measure: Rate of Increase in Hb Level in Correction Group Only
timeFrame: Up to Week 6
Other outcomes:
Locations:
city: Aichi
country: Japan
facility: Research site
city: Chiba
country: Japan
facility: Research site
city: Fukui
country: Japan
facility: Research site
city: Fukuoka
country: Japan
facility: Research site
city: Fukushima
country: Japan
facility: Research site
city: Gunma
country: Japan
facility: Research site
city: Hiroshima
country: Japan
facility: Research site
city: Hokkaido
country: Japan
facility: Research site
city: Hyogo
country: Japan
facility: Research site
city: Ibaraki
country: Japan
facility: Research site
city: Kagoshima
country: Japan
facility: Research site
city: Kanagawa
country: Japan
facility: Research site
city: Kochi
country: Japan
facility: Research site
city: Kumamoto
country: Japan
facility: Research site
city: Kyoto
country: Japan
facility: Research site
city: Miyagi
country: Japan
facility: Research site
city: Nagano
country: Japan
facility: Research site
city: Nagasaki
country: Japan
facility: Research site
city: Nara
country: Japan
facility: Research site
city: Niigata
country: Japan
facility: Research site
city: Oita
country: Japan
facility: Research site
city: Okayama
country: Japan
facility: Research site
city: Okinawa
country: Japan
facility: Research site
city: Osaka
country: Japan
facility: Research site
city: Saga
country: Japan
facility: Research site
city: Saitama
country: Japan
facility: Research site
city: Shiga
country: Japan
facility: Research site
city: Shizuoka
country: Japan
facility: Research site
city: Tokyo
country: Japan
facility: Research site
city: Toyama
country: Japan
facility: Research site
city: Yamanashi
country: Japan
facility: Research site
Study officials:
affiliation: Mitsubishi Tanabe Pharma Corporation
name: General Manager
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.