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

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)

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).

Study Overview

• Status: Completed
• Conditions: Renal Insufficiency, Chronic; Anemia
• Intervention / Treatment: Drug: Molidustat (BAY85-3934); Drug: Placebo of Darbepoetin alfa; Drug: Darbepoetin alfa; Drug: Placebo of Molidustat (BAY85-3934)

• Study Type: Interventional
• Enrollment (Actual): 229
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Chiba, Japan, 263-0043
    • Medical corporation association Shunshin-kai Inage hospital
  • Fukuoka, Japan, 810-0012
    • Ikeda Vascular Access Nephrology Dialysis
  • Fukuoka, Japan, 815-0038
    • Oohashi internal medicine circulatory Clinic
  • Kumamoto, Japan, 861-0135
    • Ueki Imafuji Clinic
  • Nagano, Japan, 380-0904
    • Medical Corporation Suzukihinyoukika
  • Nagasaki, Japan, 850-0032
    • Nagasaki Kidney Hospital
  • Osaka, Japan, 543-0052
    • Akagaki Clinic
  • Osaka, Japan, 552-0007
    • Nishi Shinryosho
  • Osaka, Japan, 555-0001
    • Chibune Clinic
  • Saitama, Japan, 339-0033
    • Iwatsuki-minami Hospital
  • Yamagata, Japan, 990-0834
    • Yamagata Tokushukai Hospital
  • Aichi
    • Nagoya, Aichi, Japan, 465-0025
      • Hakuyoukai Medical corporation Hakuyoukai Hospital
  • Chiba
    • Kashiwa, Chiba, Japan, 277-0084
      • Shinkashiwa Clinic
    • Kisarazu, Chiba, Japan, 292-0805
      • Kisarazu Clinic
  • Ehime
    • Niihama, Ehime, Japan, 792-0812
      • Kuwajima Clinic
  • Fukui
    • Sabae, Fukui, Japan, 916-0044
      • Sabae kidney Clinic
  • Fukuoka
    • Kasuya-gun, Fukuoka, Japan, 811-0120
      • Houshikai Kano hospital
    • Kitakyushu, Fukuoka, Japan, 805-0050
      • Saiseikai Yahata General Hospital
  • Gunma
    • Midori, Gunma, Japan, 379-2311
      • Sanshikai Toho Hospital
  • Hokkaido
    • Asahikawa, Hokkaido, Japan, 078-8211
      • Asahikawa-Kosei General Hospital
    • Chitose, Hokkaido, Japan, 066-0062
      • Koizumi Cardiology Medical Clinic
    • Ishikari, Hokkaido, Japan, 061-3213
      • Ishikari Hospital
    • Noboribetsu, Hokkaido, Japan, 059-0026
      • Itami Kidney Clinic
    • Sapporo, Hokkaido, Japan, 060-0008
      • Souen Central Hospital
  • Ibaraki
    • Kasama, Ibaraki, Japan, 309-1793
      • Ibaraki Prefectural Central Hospital
    • Koga, Ibaraki, Japan, 306-0014
      • Japanese Red Cross Koga Hospital
    • Mito, Ibaraki, Japan, 310-0015
      • Mito Kyodo General Hospital
    • Totte, Ibaraki, Japan, 302-0011
      • Tokiwa Clinic
    • Tsuchiura, Ibaraki, Japan, 300-0062
      • Tsuchiura Beryl Clinic
    • Tsukuba, Ibaraki, Japan, 305-0861
      • Kikuchi Medical Clinic
  • Ishikawa
    • Hakusan, Ishikawa, Japan, 924-8588
      • Public Central Hospital of Matto Ishikawa
  • Kagawa
    • Sakaide, Kagawa, Japan, 762-0007
      • Kaisei Hospital
  • Kanagawa
    • Atsugi, Kanagawa, Japan, 243-0013
      • Honatsugi Medical Clinic
    • Chigasaki, Kanagawa, Japan, 253-0052
      • Chigasaki Central Clinic
    • Sagamihara, Kanagawa, Japan, 252-0385
      • Toshiba Rinkan Hospital
    • Yokohama, Kanagawa, Japan, 224-0032
      • Yokohama Jin Clinic
    • Yokohama, Kanagawa, Japan, 225-0015
      • Eda Clinic
    • Yokohama, Kanagawa, Japan, 233-0013
      • Kaminagaya Saitou Clinic
  • Miyagi
    • Kurokawa-gun, Miyagi, Japan, 981-3632
      • Seisuikai Yoshioka Mahoroba Clinic
    • Osaki, Miyagi, Japan, 989-6117
      • Eijinkai Hospital
  • Nagano
    • Iida, Nagano, Japan, 395-8505
      • Iida Hospital
    • Matsumoto, Nagano, Japan, 390-0821
      • Kanno Dialysis & Vascular Access Clinic
    • Matsumoto, Nagano, Japan, 390-1401
      • Matsumoto City Hospital
    • Ueda, Nagano, Japan, 386-0405
      • Maruko Central Hospital
  • Osaka
    • Hirakata, Osaka, Japan, 573-1195
      • Arisawa General Hospital
    • Toyonaka, Osaka, Japan, 560-0004
      • Toyonaka Keijinkai Clinic
  • Saitama
    • Hanyu, Saitama, Japan, 348-0045
      • Hanyu General Hospital
    • Higashimatsuyama, Saitama, Japan, 355-0016
      • Higashimatsuyamakohjin Clinic
    • Koshigaya, Saitama, Japan, 343-0823
      • Saiyu Clinic
    • Toda, Saitama, Japan, 335-0023
      • Todachuo General Hospital
  • Tokyo
    • Hachioji, Tokyo, Japan, 192-0082
      • Hachioji Azumacho Clinic
    • Kodaira, Tokyo, Japan, 187-0001
      • Kodaira Kitaguchi Clinic
  • Yamaguchi
    • Ube, Yamaguchi, Japan, 755-0155
      • Saint Hill Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Molidustat group; Subjects in the molidustat group will receive molidustat and darbepoetin alfa placebo.	Drug: Molidustat (BAY85-3934); Starting dose of molidustat will be titrated based on the subject's Hb (Hemoglobin) response. Administrated orally once daily (OD).; Drug: Placebo of Darbepoetin alfa; Matching placebo of Darbepoetin alfa.
Active Comparator: Darbepoetin alfa group; Subjects in the darbepoetin alfa group will receive molidustat placebo and darbepoetin alfa.	Drug: Darbepoetin alfa; 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.; Drug: Placebo of Molidustat (BAY85-3934); Matching placebo of Molidustat.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The mean Hb level during the evaluation period	From week 33 to 36
The change in mean Hb level during the evaluation period from baseline	Baseline and week 33 to 36

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	From week 33 to 36
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	From week 33 to 36
Hb level		Up to 52 weeks
Change in Hb level		Baseline and up to 52 weeks
Proportion of subjects whose mean hemoglobin level is in the target range		From week 33 to 36
Proportion of subjects whose mean hemoglobin level is above the target range		From week 33 to 36
Proportion of subjects whose mean hemoglobin level is below the target range		From week 33 to 36
Proportion of subjects with hemoglobin levels in the target range		Up to 52 weeks
Proportion of subjects with hemoglobin levels above the target range		Up to 52 weeks
Proportion of subjects with hemoglobin levels below the target range		Up to 52 weeks
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)	Up to 52 weeks
Number of participants with serious adverse events		Up to 52 weeks
Maximum concentration (Cmax)		At baseline, week 8, week 24 and week 52
Area under the concentration-time curve (AUC)		At baseline, week 8, week 24 and week 52
EPO (Erythropoietin) serum concentration		At baseline, week 8, week 24 and week 52

Collaborators and Investigators

• Sponsor: Bayer

Publications and helpful links

General Publications

• 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.
• 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.

Helpful Links

• Click here to find results for studies related to Bayer products

Study record dates

Study Major Dates

• Study Start (Actual): June 23, 2018
• Primary Completion (Actual): August 7, 2019
• Study Completion (Actual): December 24, 2019

Study Registration Dates

• First Submitted: May 22, 2018
• First Submitted That Met QC Criteria: May 22, 2018
• First Posted (Actual): June 1, 2018

Study Record Updates

• Last Update Posted (Actual): January 29, 2021
• Last Update Submitted That Met QC Criteria: January 28, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Hematologic Diseases; Renal Insufficiency, Chronic; Renal Insufficiency; Anemia; Hematinics; Darbepoetin alfa
• Other Study ID Numbers: 19352

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No