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

• Sponsor: Mitsubishi Tanabe Pharma Corporation (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03402386
• Collaborator: (none)
• Enrollment: 42
• Locations: 17
• Arm: 1
• Actual Duration (Months): 11.5
• Patients Per Site: 2.5
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

To evaluate the efficacy and safety of MT-6548 in peritoneal dialysis subjects with anemia associated with chronic kidney disease

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 42 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 Peritoneal Dialysis Subjects With Anemia Associated With Chronic Kidney Disease in Japan
• Actual Study Start Date: Jan 3, 2018
• Actual Primary Completion Date: Nov 22, 2018
• Actual Study Completion Date: Dec 20, 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 in Correction Group Only [Up to Week 24]

5. Rate of Increase in Hb Level in Correction Group Only [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 peritoneal dialysis for more than 4 weeks prior to the screening period. However, receiving hemodialysis is excluded

• Not expected to start hemodialysis during the study

• 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

• Peritonitis within 4 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 (e.g. 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	Fukuoka		Japan
4	Research site	Fukushima		Japan
5	Research site	Gunma		Japan
6	Research site	Hokkaido		Japan
7	Research site	Hyogo		Japan
8	Research site	Ibaraki		Japan
9	Research site	Kagoshima		Japan
10	Research site	Kanagawa		Japan
11	Research site	Kyoto		Japan
12	Research site	Nagano		Japan
13	Research site	Nara		Japan
14	Research site	Okayama		Japan
15	Research site	Okinawa		Japan
16	Research site	Shiga		Japan
17	Research site	Tokyo		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: NCT03402386
• Other Study ID Numbers: MT-6548-J02
• First Posted: Jan 18, 2018
• Last Update Posted: Aug 3, 2021
• Last Verified: Aug 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	42
Correction Group	2
Conversion Group	40
COMPLETED	36
NOT COMPLETED	6

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	42
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	19 45.2%
>=65 years	23 54.8%
Sex: Female, Male (Count of Participants)
Female	12 28.6%
Male	30 71.4%
Race/Ethnicity, Customized (Count of Participants)
Asian (Japanese)	42 100%
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	41
Least Squares Mean (95% Confidence Interval) [g/dL]	11.35

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	42
Baseline	10.90
Week 2	10.96
Week 4	10.74
Week 6	10.61
Week 8	10.87
Week 10	10.89
Week 12	11.10
Week 16	11.58
Week 20	11.68
Week 24	11.39
Week 24 (LOCF)	11.01

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	42
Baseline	57.1
Week 2	60.0
Week 4	41.5
Week 6	35.9
Week 8	47.4
Week 10	44.7
Week 12	44.7
Week 16	32.4
Week 20	66.7
Week 24	65.7

4. Primary Outcome

Title	Time to Reach the Target Hb Range in Correction Group Only
Time Frame	Up to Week 24

Outcome Measure Data

Analysis Population Description

The target number of subjects by correction and conversion group was not pre-specified in the study protocol, and only 2 subjects were enrolled in the correction group as a result. The reason no data have been shown in this column is that this planned analysis wasn't performed due to such insufficient and very small amount of data from the correction group.

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	0

5. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

The target number of subjects by correction and conversion group was not pre-specified in the study protocol, and only 2 subjects were enrolled in the correction group as a result. The reason no data have been shown in this column is that this planned analysis wasn't performed due to such insufficient and very small amount of data from the correction group.

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	0

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	1/42 (2.4%)
Serious Adverse Events
	MT-6548
	Affected / at Risk (%)	# Events
Total	12/42 (28.6%)
Blood and lymphatic system disorders
Anaemia	1/42 (2.4%)
Cardiac disorders
Cardiac failure chronic	1/42 (2.4%)
Myocardial ischaemia	1/42 (2.4%)
Gastrointestinal disorders
Gastric polyps	1/42 (2.4%)
Inguinal hernia	1/42 (2.4%)
Infections and infestations
Catheter site infection	1/42 (2.4%)
Peritonitis	3/42 (7.1%)
Sepsis	1/42 (2.4%)
Injury, poisoning and procedural complications
Peritoneal dialysis complication	1/42 (2.4%)
Shunt occlusion	1/42 (2.4%)
Traumatic haemothorax	1/42 (2.4%)
Nervous system disorders
Cerebral infarction	1/42 (2.4%)
Vascular disorders
Peripheral arterial occlusive disease	2/42 (4.8%)
Other (Not Including Serious) Adverse Events
	MT-6548
	Affected / at Risk (%)	# Events
Total	21/42 (50%)
Gastrointestinal disorders
Abdominal pain upper	3/42 (7.1%)
Diarrhoea	8/42 (19%)
Nausea	3/42 (7.1%)
Vomiting	4/42 (9.5%)
Infections and infestations
Catheter site infection	9/42 (21.4%)
Nasopharyngitis	6/42 (14.3%)
Metabolism and nutrition disorders
Decreased appetite	3/42 (7.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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