Efficacy and Safety Study to Evaluate MT-6548 in Hemodialysis Subjects Not Receiving ESAs With Anemia Associated With Chronic Kidney Disease in Japan

• Sponsor: Mitsubishi Tanabe Pharma Corporation (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03461146
• Collaborator: (none)
• Enrollment: 24
• Locations: 16
• Arm: 1
• Actual Duration (Months): 9.4
• Patients Per Site: 1.5
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

For hemodialysis subjects not receiving ESAs with anemia associated with chronic kidney disease, evaluate Hb correction and maintenance effect and safety of MT-6548.

Condition or Disease	Intervention/Treatment	Phase
Anemia; Hemodialysis Dependent Chronic Kidney Disease	Drug: MT-6548	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 24 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase III, Open-label Study of MT-6548 in Hemodialysis Subjects With Anemia Associated With Chronic Kidney Disease in Japan
• Actual Study Start Date: Mar 5, 2018
• Actual Primary Completion Date: Dec 3, 2018
• Actual Study Completion Date: Dec 17, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: MT-6548	Drug: MT-6548; Oral tablet; Other Names: vadadustat AKB-6548

Outcome Measures

Primary Outcome Measures

1. Mean Hb Level of Week 20 and Week 24 [Up to Week 24]

2. Hb Level at Each Assessment Time Point [Up to Week 24]

3. Percentage of Subjects With Hb Level at Each Assessment Time Point Within the Target Range During the Treatment Period [Up to Week 24]

4. Time to Reach the Target Hb Range [Up to Week 24]

5. Rate of Increase in Hb Level [Up to Week 6]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

• Not being treated with ESAs or if being treated with ESAs, leave defined interval between last ESAs administration and the first day of the screening period

• Mean of the two screening Hb levels closest in time to the baseline visit is ≥8.0 g/dL and <10.0 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

	Site	City	State	Country	Postal Code
1	Research site	Aichi		Japan
2	Research site	Chiba		Japan
3	Research site	Fukushima		Japan
4	Research site	Gunma		Japan
5	Research site	Hokkaido		Japan
6	Research site	Hyogo		Japan
7	Research site	Ibaraki		Japan
8	Research site	Kagoshima		Japan
9	Research site	Nagano		Japan
10	Research site	Okayama		Japan
11	Research site	Okinawa		Japan
12	Research site	Osaka		Japan
13	Research site	Saitama		Japan
14	Research site	Shiga		Japan
15	Research site	Shizuoka		Japan
16	Research site	Yamagata		Japan

Sponsors and Collaborators

• Mitsubishi Tanabe Pharma Corporation

Investigators

• Study Director: General Manager, Mitsubishi Tanabe Pharma Corporation

Study Documents (Full-Text)

• Study Protocol - Dec 26, 2017
• Statistical Analysis Plan - Mar 26, 2019

More Information

Publications

None provided.

• Responsible Party: Mitsubishi Tanabe Pharma Corporation
• ClinicalTrials.gov Identifier: NCT03461146
• Other Study ID Numbers: MT-6548-J04
• First Posted: Mar 9, 2018
• Last Update Posted: Jul 27, 2021
• Last Verified: Jul 1, 2021

• 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

Study Results

Participant Flow

Arm/Group Title	MT-6548
Arm/Group Description	MT-6548: Oral tablet. The dose was adjusted to 150-600 mg/day according to the pre-specified dose adjustment algorithm.
Period Title: Overall Study
STARTED	24
COMPLETED	21
NOT COMPLETED	3

Baseline Characteristics

Arm/Group Title	MT-6548
Arm/Group Description	MT-6548: Oral tablet. The dose was adjusted to 150-600 mg/day according to the pre-specified dose adjustment algorithm.
Overall Participants	24
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	11 45.8%
>=65 years	13 54.2%
Sex: Female, Male (Count of Participants)
Female	5 20.8%
Male	19 79.2%
Race/Ethnicity, Customized (Count of Participants)
Asian (Japanese)	24 100%
Asian (Other)	0 0%
Other	0 0%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

This analysis was performed in subjects who measured Hb at least one visit after baseline.

Arm/Group Title	MT-6548
Arm/Group Description	MT-6548: Oral tablet. The dose was adjusted to 150-600 mg/day according to the pre-specified dose adjustment algorithm.
Measure Participants	23
Least Squares Mean (95% Confidence Interval) [g/dL]	10.75

2. Primary Outcome

Title	Hb Level at Each Assessment Time Point
Time Frame	Up to Week 24

Outcome Measure Data

Analysis Population Description

This analysis was performed only in subjects who have Hb data at each visit.

Arm/Group Title	MT-6548
Arm/Group Description	MT-6548: Oral tablet. The dose was adjusted to 150-600 mg/day according to the pre-specified dose adjustment algorithm.
Measure Participants	24
Baseline	9.15
Week 2	9.25
Week 4	9.53
Week 6	9.90
Week 8	10.33
Week 10	10.56
Week 12	10.68
Week 16	11.17
Week 20	11.08
Week 24	11.03
Week 24 (LOCF)	10.56

3. Primary Outcome

Title	Percentage of Subjects With Hb Level at Each Assessment Time Point Within the Target Range During the Treatment Period
Time Frame	Up to Week 24

Outcome Measure Data

Analysis Population Description

This analysis was performed only in subjects who have Hb data at each visit.

Arm/Group Title	MT-6548
Arm/Group Description	MT-6548: Oral tablet. The dose was adjusted to 150-600 mg/day according to the pre-specified dose adjustment algorithm.
Measure Participants	24
Baseline	16.7
Week 2	21.7
Week 4	36.4
Week 6	47.6
Week 8	55.0
Week 10	63.2
Week 12	68.4
Week 16	63.2
Week 20	78.9
Week 24	73.7

4. Primary Outcome

Title	Time to Reach the Target Hb Range
Time Frame	Up to Week 24

Outcome Measure Data

Analysis Population Description

This analysis was performed except for subjects with Hb of 10.0 g/dL or more at baseline.

Arm/Group Title	MT-6548
Arm/Group Description	MT-6548: Oral tablet. The dose was adjusted to 150-600 mg/day according to the pre-specified dose adjustment algorithm.
Measure Participants	20
Mean (95% Confidence Interval) [days]	67.2

5. Primary Outcome

Title	Rate of Increase in Hb Level
Time Frame	Up to Week 6

Outcome Measure Data

Analysis Population Description

This analysis was performed in subjects who measured Hb up to week 4 or week 6.

Arm/Group Title	MT-6548
Arm/Group Description	MT-6548: Oral tablet. The dose was adjusted to 150-600 mg/day according to the pre-specified dose adjustment algorithm.
Measure Participants	22
Calculated based on Hb at baseline and Week 4	0.05
Calculated based on Hb up to Week6	0.09

Adverse Events

Time Frame	24 weeks
Arm/Group Title	MT-6548
Arm/Group Description	MT-6548: Oral tablet. The dose was adjusted to 150-600 mg/day according to the pre-specified dose adjustment algorithm.
All Cause Mortality
	MT-6548
	Affected / at Risk (%)	# Events
Total	0/24 (0%)
Serious Adverse Events
	MT-6548
	Affected / at Risk (%)	# Events
Total	7/24 (29.2%)
Gastrointestinal disorders
Duodenal ulcer haemorrhage	1/24 (4.2%)
Infections and infestations
Pneumonia	1/24 (4.2%)
Injury, poisoning and procedural complications
Arteriovenous fistula occlusion	1/24 (4.2%)
Clavicle fracture	1/24 (4.2%)
Pelvic fracture	1/24 (4.2%)
Shunt stenosis	1/24 (4.2%)
Vascular access malfunction	1/24 (4.2%)
Vascular disorders
Aneurysm	1/24 (4.2%)
Peripheral arterial occlusive disease	1/24 (4.2%)
Other (Not Including Serious) Adverse Events
	MT-6548
	Affected / at Risk (%)	# Events
Total	15/24 (62.5%)
Gastrointestinal disorders
Diarrhoea	4/24 (16.7%)
Vomiting	2/24 (8.3%)
Infections and infestations
Nasopharyngitis	5/24 (20.8%)
Injury, poisoning and procedural complications
Shunt stenosis	5/24 (20.8%)
Skin abrasion	3/24 (12.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.