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Maintenance Treatment of Renal Anemia in Dialysis Subjects (MIYABI HD-M)

Primary Purpose

Anemia, Renal Insufficiency, Chronic

Status
Completed
Phase
Phase 3
Locations
Japan
Study Type
Interventional
Intervention
Molidustat (BAY85-3934)
Darbepoetin alfa
Placebo of Molidustat (BAY85-3934)
Placebo of Darbepoetin alfa
Sponsored by
Bayer
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Anemia

Eligibility Criteria

20 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Subject with ESKD (end-stage kidney disease) on regular dialysis (including, hemodiafiltration, hemofiltration, hemodialysis, and other modalities except for peritoneal dialysis) weekly or more than weekly for at least 12 weeks prior to randomization
  • Body weight (after dialysis) > 40 and ≤ 160 kg at screening
  • Male or female subject ≥ 20 years of age at screening
  • At least one kidney
  • Treated with weekly or bi-weekly dose of darbepoetin alfa, monthly or bi-weekly dose of epoetin beta pegol, OR weekly, biweekly, twice or three times per week dose of epoetin alfa/beta, and having had no more than one dose change within 8 weeks prior to randomization
  • Mean screening Hb level ≥ 9.5 and < 12.0 g/dL (mean of all central laboratory Hb levels before dialysis [at least 2 measurements must be taken ≥ 2 days apart] during the screening period, AND all Hb level must be measured by the central laboratory, AND the difference between the lowest level and highest level is < 1.2 g/dL), with the last screening Hb level measurement within 14 days prior to randomization
  • Ferritin ≥ 100 ng/mL or transferrin saturation ≥ 20% at screening
  • Serum folate level and serum vitamin B12 level above lower limit of normal (LLN) at screening

Exclusion Criteria:

  • New York Heart Association (NYHA) Class III or IV congestive heart failure
  • History of cardio- (cerebro-) vascular events (e.g., unstable angina, myocardial infarction, stroke, pulmonary thromboembolism, and acute limb ischemia) within 6 months prior to randomization
  • Sustained, poorly controlled arterial hypertension (defined as systolic BP (blood pressure) ≥ 180mmHg or diastolic BP ≥ 110mmHg) or hypotension (defined as systolic BP < 90mmHg) at randomization
  • Proliferative choroidal or retinal disease, such as neovascular agerelated macular degeneration or proliferative diabetic retinopathy requiring invasive treatment (e.g., intraocular injections or laser photocoagulation) at screening

Sites / Locations

  • Hakuyoukai Medical corporation Hakuyoukai Hospital
  • Shinkashiwa Clinic
  • Kisarazu Clinic
  • Kuwajima Clinic
  • Sabae kidney Clinic
  • Houshikai Kano hospital
  • Saiseikai Yahata General Hospital
  • Sanshikai Toho Hospital
  • Asahikawa-Kosei General Hospital
  • Koizumi Cardiology Medical Clinic
  • Ishikari Hospital
  • Itami Kidney Clinic
  • Souen Central Hospital
  • Ibaraki Prefectural Central Hospital
  • Japanese Red Cross Koga Hospital
  • Mito Kyodo General Hospital
  • Tokiwa Clinic
  • Tsuchiura Beryl Clinic
  • Kikuchi Medical Clinic
  • Public Central Hospital of Matto Ishikawa
  • Kaisei Hospital
  • Honatsugi Medical Clinic
  • Chigasaki Central Clinic
  • Toshiba Rinkan Hospital
  • Yokohama Jin Clinic
  • Eda Clinic
  • Kaminagaya Saitou Clinic
  • Seisuikai Yoshioka Mahoroba Clinic
  • Eijinkai Hospital
  • Iida Hospital
  • Kanno Dialysis & Vascular Access Clinic
  • Matsumoto City Hospital
  • Maruko Central Hospital
  • Arisawa General Hospital
  • Toyonaka Keijinkai Clinic
  • Hanyu General Hospital
  • Higashimatsuyamakohjin Clinic
  • Saiyu Clinic
  • Todachuo General Hospital
  • Hachioji Azumacho Clinic
  • Kodaira Kitaguchi Clinic
  • Saint Hill Hospital
  • Medical corporation association Shunshin-kai Inage hospital
  • Ikeda Vascular Access Nephrology Dialysis
  • Oohashi internal medicine circulatory Clinic
  • Ueki Imafuji Clinic
  • Medical Corporation Suzukihinyoukika
  • Nagasaki Kidney Hospital
  • Akagaki Clinic
  • Nishi Shinryosho
  • Chibune Clinic
  • Iwatsuki-minami Hospital
  • Yamagata Tokushukai Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Molidustat group

Darbepoetin alfa group

Arm Description

Subjects in the molidustat group will receive molidustat and darbepoetin alfa placebo.

Subjects in the darbepoetin alfa group will receive molidustat placebo and darbepoetin alfa.

Outcomes

Primary Outcome Measures

The mean Hb level during the evaluation period
The change in mean Hb level during the evaluation period from baseline

Secondary Outcome Measures

Responder rate: proportion of responders among the subjects
Responder is defined as meeting all of the following criteria: (i) Mean of the Hb levels in the target range (ii) ≥ 50% of the Hb levels in the target range (iii) No rescue treatment
Proportion of subjects who meet each component of the response
Response: (i) Mean of the Hb levels in the target range (ii) ≥ 50% of the Hb levels in the target range (iii) No rescue treatment
Hb level
Change in Hb level
Proportion of subjects whose mean hemoglobin level is in the target range
Proportion of subjects whose mean hemoglobin level is above the target range
Proportion of subjects whose mean hemoglobin level is below the target range
Proportion of subjects with hemoglobin levels in the target range
Proportion of subjects with hemoglobin levels above the target range
Proportion of subjects with hemoglobin levels below the target range
Proportion of subjects whose maximum rise in Hb between each consecutive visits is above 0.5 g/dL/week
Defined as change in Hb level / duration between two visits (weeks)
Number of participants with serious adverse events
Maximum concentration (Cmax)
Area under the concentration-time curve (AUC)
EPO (Erythropoietin) serum concentration

Full Information

First Posted
May 22, 2018
Last Updated
January 28, 2021
Sponsor
Bayer
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1. Study Identification

Unique Protocol Identification Number
NCT03543657
Brief Title
Maintenance Treatment of Renal Anemia in Dialysis Subjects
Acronym
MIYABI HD-M
Official Title
A Randomized, Active-controlled, Double-blinded, Double-dummy, Parallel-group, Multicenter Study to Investigate the Efficacy and Safety of Oral Molidustat in Comparison to Darbepoetin Alfa in Dialysis Subjects Treated With Erythropoiesis-Stimulating Agents (ESAs)
Study Type
Interventional

2. Study Status

Record Verification Date
January 2021
Overall Recruitment Status
Completed
Study Start Date
June 23, 2018 (Actual)
Primary Completion Date
August 7, 2019 (Actual)
Study Completion Date
December 24, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bayer

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this study is to evaluate the efficacy and safety of molidustat in comparison to darbepoetin alfa in dialysis subjects with renal anemia who are treated with Erythropoiesis-Stimulating Agents (ESAs).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Anemia, Renal Insufficiency, Chronic

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
229 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Molidustat group
Arm Type
Experimental
Arm Description
Subjects in the molidustat group will receive molidustat and darbepoetin alfa placebo.
Arm Title
Darbepoetin alfa group
Arm Type
Active Comparator
Arm Description
Subjects in the darbepoetin alfa group will receive molidustat placebo and darbepoetin alfa.
Intervention Type
Drug
Intervention Name(s)
Molidustat (BAY85-3934)
Intervention Description
Starting dose of molidustat will be titrated based on the subject's Hb (Hemoglobin) response. Administrated orally once daily (OD).
Intervention Type
Drug
Intervention Name(s)
Darbepoetin alfa
Intervention Description
Starting dose of darbepoetin alfa will be titrated based on the subject's Hb (Hemoglobin) response. Administrated weekly or once every two weeks by intravenous injection.
Intervention Type
Drug
Intervention Name(s)
Placebo of Molidustat (BAY85-3934)
Intervention Description
Matching placebo of Molidustat.
Intervention Type
Drug
Intervention Name(s)
Placebo of Darbepoetin alfa
Intervention Description
Matching placebo of Darbepoetin alfa.
Primary Outcome Measure Information:
Title
The mean Hb level during the evaluation period
Time Frame
From week 33 to 36
Title
The change in mean Hb level during the evaluation period from baseline
Time Frame
Baseline and week 33 to 36
Secondary Outcome Measure Information:
Title
Responder rate: proportion of responders among the subjects
Description
Responder is defined as meeting all of the following criteria: (i) Mean of the Hb levels in the target range (ii) ≥ 50% of the Hb levels in the target range (iii) No rescue treatment
Time Frame
From week 33 to 36
Title
Proportion of subjects who meet each component of the response
Description
Response: (i) Mean of the Hb levels in the target range (ii) ≥ 50% of the Hb levels in the target range (iii) No rescue treatment
Time Frame
From week 33 to 36
Title
Hb level
Time Frame
Up to 52 weeks
Title
Change in Hb level
Time Frame
Baseline and up to 52 weeks
Title
Proportion of subjects whose mean hemoglobin level is in the target range
Time Frame
From week 33 to 36
Title
Proportion of subjects whose mean hemoglobin level is above the target range
Time Frame
From week 33 to 36
Title
Proportion of subjects whose mean hemoglobin level is below the target range
Time Frame
From week 33 to 36
Title
Proportion of subjects with hemoglobin levels in the target range
Time Frame
Up to 52 weeks
Title
Proportion of subjects with hemoglobin levels above the target range
Time Frame
Up to 52 weeks
Title
Proportion of subjects with hemoglobin levels below the target range
Time Frame
Up to 52 weeks
Title
Proportion of subjects whose maximum rise in Hb between each consecutive visits is above 0.5 g/dL/week
Description
Defined as change in Hb level / duration between two visits (weeks)
Time Frame
Up to 52 weeks
Title
Number of participants with serious adverse events
Time Frame
Up to 52 weeks
Title
Maximum concentration (Cmax)
Time Frame
At baseline, week 8, week 24 and week 52
Title
Area under the concentration-time curve (AUC)
Time Frame
At baseline, week 8, week 24 and week 52
Title
EPO (Erythropoietin) serum concentration
Time Frame
At baseline, week 8, week 24 and week 52

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Subject with ESKD (end-stage kidney disease) on regular dialysis (including, hemodiafiltration, hemofiltration, hemodialysis, and other modalities except for peritoneal dialysis) weekly or more than weekly for at least 12 weeks prior to randomization Body weight (after dialysis) > 40 and ≤ 160 kg at screening Male or female subject ≥ 20 years of age at screening At least one kidney Treated with weekly or bi-weekly dose of darbepoetin alfa, monthly or bi-weekly dose of epoetin beta pegol, OR weekly, biweekly, twice or three times per week dose of epoetin alfa/beta, and having had no more than one dose change within 8 weeks prior to randomization Mean screening Hb level ≥ 9.5 and < 12.0 g/dL (mean of all central laboratory Hb levels before dialysis [at least 2 measurements must be taken ≥ 2 days apart] during the screening period, AND all Hb level must be measured by the central laboratory, AND the difference between the lowest level and highest level is < 1.2 g/dL), with the last screening Hb level measurement within 14 days prior to randomization Ferritin ≥ 100 ng/mL or transferrin saturation ≥ 20% at screening Serum folate level and serum vitamin B12 level above lower limit of normal (LLN) at screening Exclusion Criteria: New York Heart Association (NYHA) Class III or IV congestive heart failure History of cardio- (cerebro-) vascular events (e.g., unstable angina, myocardial infarction, stroke, pulmonary thromboembolism, and acute limb ischemia) within 6 months prior to randomization Sustained, poorly controlled arterial hypertension (defined as systolic BP (blood pressure) ≥ 180mmHg or diastolic BP ≥ 110mmHg) or hypotension (defined as systolic BP < 90mmHg) at randomization Proliferative choroidal or retinal disease, such as neovascular agerelated macular degeneration or proliferative diabetic retinopathy requiring invasive treatment (e.g., intraocular injections or laser photocoagulation) at screening
Facility Information:
Facility Name
Hakuyoukai Medical corporation Hakuyoukai Hospital
City
Nagoya
State/Province
Aichi
ZIP/Postal Code
465-0025
Country
Japan
Facility Name
Shinkashiwa Clinic
City
Kashiwa
State/Province
Chiba
ZIP/Postal Code
277-0084
Country
Japan
Facility Name
Kisarazu Clinic
City
Kisarazu
State/Province
Chiba
ZIP/Postal Code
292-0805
Country
Japan
Facility Name
Kuwajima Clinic
City
Niihama
State/Province
Ehime
ZIP/Postal Code
792-0812
Country
Japan
Facility Name
Sabae kidney Clinic
City
Sabae
State/Province
Fukui
ZIP/Postal Code
916-0044
Country
Japan
Facility Name
Houshikai Kano hospital
City
Kasuya-gun
State/Province
Fukuoka
ZIP/Postal Code
811-0120
Country
Japan
Facility Name
Saiseikai Yahata General Hospital
City
Kitakyushu
State/Province
Fukuoka
ZIP/Postal Code
805-0050
Country
Japan
Facility Name
Sanshikai Toho Hospital
City
Midori
State/Province
Gunma
ZIP/Postal Code
379-2311
Country
Japan
Facility Name
Asahikawa-Kosei General Hospital
City
Asahikawa
State/Province
Hokkaido
ZIP/Postal Code
078-8211
Country
Japan
Facility Name
Koizumi Cardiology Medical Clinic
City
Chitose
State/Province
Hokkaido
ZIP/Postal Code
066-0062
Country
Japan
Facility Name
Ishikari Hospital
City
Ishikari
State/Province
Hokkaido
ZIP/Postal Code
061-3213
Country
Japan
Facility Name
Itami Kidney Clinic
City
Noboribetsu
State/Province
Hokkaido
ZIP/Postal Code
059-0026
Country
Japan
Facility Name
Souen Central Hospital
City
Sapporo
State/Province
Hokkaido
ZIP/Postal Code
060-0008
Country
Japan
Facility Name
Ibaraki Prefectural Central Hospital
City
Kasama
State/Province
Ibaraki
ZIP/Postal Code
309-1793
Country
Japan
Facility Name
Japanese Red Cross Koga Hospital
City
Koga
State/Province
Ibaraki
ZIP/Postal Code
306-0014
Country
Japan
Facility Name
Mito Kyodo General Hospital
City
Mito
State/Province
Ibaraki
ZIP/Postal Code
310-0015
Country
Japan
Facility Name
Tokiwa Clinic
City
Totte
State/Province
Ibaraki
ZIP/Postal Code
302-0011
Country
Japan
Facility Name
Tsuchiura Beryl Clinic
City
Tsuchiura
State/Province
Ibaraki
ZIP/Postal Code
300-0062
Country
Japan
Facility Name
Kikuchi Medical Clinic
City
Tsukuba
State/Province
Ibaraki
ZIP/Postal Code
305-0861
Country
Japan
Facility Name
Public Central Hospital of Matto Ishikawa
City
Hakusan
State/Province
Ishikawa
ZIP/Postal Code
924-8588
Country
Japan
Facility Name
Kaisei Hospital
City
Sakaide
State/Province
Kagawa
ZIP/Postal Code
762-0007
Country
Japan
Facility Name
Honatsugi Medical Clinic
City
Atsugi
State/Province
Kanagawa
ZIP/Postal Code
243-0013
Country
Japan
Facility Name
Chigasaki Central Clinic
City
Chigasaki
State/Province
Kanagawa
ZIP/Postal Code
253-0052
Country
Japan
Facility Name
Toshiba Rinkan Hospital
City
Sagamihara
State/Province
Kanagawa
ZIP/Postal Code
252-0385
Country
Japan
Facility Name
Yokohama Jin Clinic
City
Yokohama
State/Province
Kanagawa
ZIP/Postal Code
224-0032
Country
Japan
Facility Name
Eda Clinic
City
Yokohama
State/Province
Kanagawa
ZIP/Postal Code
225-0015
Country
Japan
Facility Name
Kaminagaya Saitou Clinic
City
Yokohama
State/Province
Kanagawa
ZIP/Postal Code
233-0013
Country
Japan
Facility Name
Seisuikai Yoshioka Mahoroba Clinic
City
Kurokawa-gun
State/Province
Miyagi
ZIP/Postal Code
981-3632
Country
Japan
Facility Name
Eijinkai Hospital
City
Osaki
State/Province
Miyagi
ZIP/Postal Code
989-6117
Country
Japan
Facility Name
Iida Hospital
City
Iida
State/Province
Nagano
ZIP/Postal Code
395-8505
Country
Japan
Facility Name
Kanno Dialysis & Vascular Access Clinic
City
Matsumoto
State/Province
Nagano
ZIP/Postal Code
390-0821
Country
Japan
Facility Name
Matsumoto City Hospital
City
Matsumoto
State/Province
Nagano
ZIP/Postal Code
390-1401
Country
Japan
Facility Name
Maruko Central Hospital
City
Ueda
State/Province
Nagano
ZIP/Postal Code
386-0405
Country
Japan
Facility Name
Arisawa General Hospital
City
Hirakata
State/Province
Osaka
ZIP/Postal Code
573-1195
Country
Japan
Facility Name
Toyonaka Keijinkai Clinic
City
Toyonaka
State/Province
Osaka
ZIP/Postal Code
560-0004
Country
Japan
Facility Name
Hanyu General Hospital
City
Hanyu
State/Province
Saitama
ZIP/Postal Code
348-0045
Country
Japan
Facility Name
Higashimatsuyamakohjin Clinic
City
Higashimatsuyama
State/Province
Saitama
ZIP/Postal Code
355-0016
Country
Japan
Facility Name
Saiyu Clinic
City
Koshigaya
State/Province
Saitama
ZIP/Postal Code
343-0823
Country
Japan
Facility Name
Todachuo General Hospital
City
Toda
State/Province
Saitama
ZIP/Postal Code
335-0023
Country
Japan
Facility Name
Hachioji Azumacho Clinic
City
Hachioji
State/Province
Tokyo
ZIP/Postal Code
192-0082
Country
Japan
Facility Name
Kodaira Kitaguchi Clinic
City
Kodaira
State/Province
Tokyo
ZIP/Postal Code
187-0001
Country
Japan
Facility Name
Saint Hill Hospital
City
Ube
State/Province
Yamaguchi
ZIP/Postal Code
755-0155
Country
Japan
Facility Name
Medical corporation association Shunshin-kai Inage hospital
City
Chiba
ZIP/Postal Code
263-0043
Country
Japan
Facility Name
Ikeda Vascular Access Nephrology Dialysis
City
Fukuoka
ZIP/Postal Code
810-0012
Country
Japan
Facility Name
Oohashi internal medicine circulatory Clinic
City
Fukuoka
ZIP/Postal Code
815-0038
Country
Japan
Facility Name
Ueki Imafuji Clinic
City
Kumamoto
ZIP/Postal Code
861-0135
Country
Japan
Facility Name
Medical Corporation Suzukihinyoukika
City
Nagano
ZIP/Postal Code
380-0904
Country
Japan
Facility Name
Nagasaki Kidney Hospital
City
Nagasaki
ZIP/Postal Code
850-0032
Country
Japan
Facility Name
Akagaki Clinic
City
Osaka
ZIP/Postal Code
543-0052
Country
Japan
Facility Name
Nishi Shinryosho
City
Osaka
ZIP/Postal Code
552-0007
Country
Japan
Facility Name
Chibune Clinic
City
Osaka
ZIP/Postal Code
555-0001
Country
Japan
Facility Name
Iwatsuki-minami Hospital
City
Saitama
ZIP/Postal Code
339-0033
Country
Japan
Facility Name
Yamagata Tokushukai Hospital
City
Yamagata
ZIP/Postal Code
990-0834
Country
Japan

12. IPD Sharing Statement

Citations:
PubMed Identifier
36005278
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.
Results Reference
derived
PubMed Identifier
31203241
Citation
Akizawa T, Taguchi M, Matsuda Y, Iekushi K, Yamada T, Yamamoto H. Molidustat for the treatment of renal anaemia in patients with dialysis-dependent chronic kidney disease: design and rationale of three phase III studies. BMJ Open. 2019 Jun 14;9(6):e026602. doi: 10.1136/bmjopen-2018-026602.
Results Reference
derived
Links:
URL
http://clinicaltrials.bayer.com/
Description
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Maintenance Treatment of Renal Anemia in Dialysis Subjects

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