A Study of Molidustat for Maintenance Treatment of Renal Anemia in Non-dialysis Subjects (MIYABI ND-M)

A Randomized, Open-label, Active-controlled, Parallel-group, Multicenter Study to Investigate the Efficacy and Safety of Oral Molidustat in Comparison to Darbepoetin Alfa in Non-dialysis Subjects Previously Treated With Erythropoiesis-Stimulating Agents (ESAs)

The purpose of this study is to evaluate the efficacy and safety of molidustat in non-dialysis subjects previously treated with Erythropoiesis-Stimulating Agents (ESAs)

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 164
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Fukui, Japan, 910-8526
    • Fukui Prefectural Hospital
  • Fukuoka, Japan, 810-8563
    • National Hospital Organization Kyushu Medical Center
  • Fukuoka, Japan, 812-8582
    • Kyushu University Hospital
  • Fukuoka, Japan, 814-0180
    • Fukuoka University Hospital
  • Gifu, Japan, 500-8523
    • Asahi University Hospital
  • Kochi, Japan, 780-8077
    • National Hospital Organization Kochi National Hospital
  • Miyazaki, Japan, 880-8510
    • Miyazaki Prefectural Miyazaki Hospital
  • Nara, Japan, 630-8581
    • Nara Prefecture General Medical Center
  • Oita, Japan, 870-0033
    • Japanese Red Cross Oita Hospital
  • Osaka, Japan, 543-8555
    • Osaka Red Cross Hospital
  • Osaka, Japan, 540-0006
    • National Hospital Organization Osaka National Hospital
  • Osaka, Japan, 558-8558
    • Osaka General Medical Center
  • Osaka, Japan, 533-0024
    • Yodogawa Christian Hospital
  • Osaka, Japan, 530-8480
    • Kitano Hospital
  • Osaka, Japan, 550-0006
    • Nippon Life Hospital
  • Osaka, Japan, 555-0001
    • Chibune Clinic
  • Osaka, Japan, 559-0012
    • Social Corporation Keigakukai Minamiosaka Hospital
  • Shizuoka, Japan, 424-0855
    • Suruga Clinic
  • Shizuoka, Japan, 422-8527
    • Shizuoka Saiseikai General Hospital
  • Wakayama, Japan, 641-8510
    • Wakayama Medical University Hospital
  • Aichi
    • Yatomi, Aichi, Japan, 498-8502
      • Kainan Hospital
  • Chiba
    • Matsudo, Chiba, Japan, 271-0077
      • Seikeikai New Tokyo Heart Clinic
  • Ehime
    • Matsuyama, Ehime, Japan, 791-8026
      • Saiseikai Matsuyama Hospital
    • Matsuyama, Ehime, Japan, 790-0024
      • Ehime Prefectural Central Hospital
  • Fukuoka
    • Iizuka, Fukuoka, Japan, 820-8505
      • Iizuka Hospital
    • Kitakyushu, Fukuoka, Japan, 802-8555
      • Kokura Memorial Hospital
    • Kitakyushu, Fukuoka, Japan, 805-8508
      • Steel Memorial Yawata Hospital
    • Koga, Fukuoka, Japan, 811-3195
      • National Fukuoka-Higashi Medical Center
    • Kurume, Fukuoka, Japan, 830-8543
      • St.Mary's Hospital
    • Kurume, Fukuoka, Japan, 830-0011
      • Kurume University Hospital
  • Gifu
    • Hashima-gun, Gifu, Japan, 501-6061
      • Matsunami Health Promotion Clinic
  • Hiroshima
    • Aki-gun, Hiroshima, Japan, 735-8585
      • Mazda Hospital of Mazda Motor Corporation
    • Fukuyama, Hiroshima, Japan, 721-0927
      • Nippon Kokan Fukuyama Hospital
    • Higashihiroshima, Hiroshima, Japan, 739-0041
      • Higashihiroshima Medical Center
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 006-8555
      • Teine Keijinkai Clinic
  • Hyogo
    • Kobe, Hyogo, Japan, 650-0047
      • Kobe City Medical Center General Hospital
    • Kobe, Hyogo, Japan, 654-0155
      • National Hospital Organization Kobe Medical Center
  • Ibaraki
    • Mito, Ibaraki, Japan, 310-0015
      • Mito Kyodo General Hospital
  • Ishikawa
    • Hakusan, Ishikawa, Japan, 924-8588
      • Public Central Hospital of Matto Ishikawa
  • Kagawa
    • Takamatsu, Kagawa, Japan, 761-1701
      • KenAiKai medical corporation Akiyama clinic
  • Kagoshima
    • Kanoya, Kagoshima, Japan, 893-0024
      • Ikeda Hospital
  • Kanagawa
    • Fujisawa, Kanagawa, Japan, 251-8550
      • Fujisawa City Hospital
    • Kawasaki, Kanagawa, Japan, 210-0852
      • Koukan Clinic
    • Yokohama, Kanagawa, Japan, 227-8501
      • Showa University Fujigaoka Hospital
    • Yokosuka, Kanagawa, Japan, 238-8558
      • Yokosuka Kyosai Hospital
  • Kumamoto
    • Arao, Kumamoto, Japan, 864-0041
      • Arao Municipal Hospital
  • Mie
    • Yokkaichi, Mie, Japan, 510-0016
      • JCHO Yokkaichi Hazu Medical Center
  • Miyagi
    • Ishinomaki, Miyagi, Japan, 986-8522
      • Japanese Red Cross Ishinomaki Hospital
  • Nagano
    • Komoro, Nagano, Japan, 384-8588
      • Asama Nanroku Komoro Medical Center
  • Niigata
    • Shibata, Niigata, Japan, 957-8588
      • Niigata Prefectural Shibata Hospital
  • Okinawa
    • Naha, Okinawa, Japan, 902-8511
      • R.I.A.C Naha City Hospital
  • Osaka
    • Tondabayashi, Osaka, Japan, 584-0082
      • Osaka Pref. Saiseikai Tondabayashi Hospital
  • Saitama
    • Kitamoto, Saitama, Japan, 364-8501
      • Kitasato University Medical Center
  • Shizuoka
    • Iwata, Shizuoka, Japan, 438-8550
      • Iwata City Hospital
  • Tokyo
    • Itabashi-ku, Tokyo, Japan, 173-8610
      • Nihon University Itabashi Hospital
    • Itabashi-ku, Tokyo, Japan, 173-0015
      • Toshima Hospital
    • Koto-ku, Tokyo, Japan, 135-8577
      • Showa University Koto Toyosu Hospital
    • Meguro-ku, Tokyo, Japan, 152-8902
      • National Hospital Organization Tokyo Medical Center
  • Yamanashi
    • Chuo, Yamanashi, Japan, 409-3898
      • University of Yamanashi Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects with estimated glomerular filtration rate (eGFR)< 60 mL/min/1.73m^2 (Chronic kidney disease [CKD] stages 3 to 5)
• Have used the same ESA for 8 weeks prior to screening
• Treated with darbepoetin alfa with bi-weekly or monthly dose, epoetin beta pegol with monthly, OR epoetin alfa/beta weekly or bi-weekly, and having had no more than one dose change within 8 weeks prior to randomization
• Body weight > 40 and ≤ 160 kg at screening
• Male or female subject ≥ 20 years of age at screening
• Not on dialysis and not expected to start dialysis during the study period
• Mean screening Hb level ≥ 10.0 and < 13.0 g/dL (mean of all central laboratory Hb levels [at least 2 measurements must be taken ≥ 2 days apart] during the 8-week 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%

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 and 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 age-related macular degeneration or proliferative diabetic retinopathy requiring invasive treatment (e.g., intraocular injections or laser photocoagulation)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Molidustat (BAY85-3934); Molidustat group	Drug: Molidustat (BAY85-3934); Starting dose of 25 mg or 50 mg molidustat once daily (OD) will be titrated based on the subject's Hb response
Active Comparator: Darbepoetin alfa; Darbepoetin alfa group	Drug: Darbepoetin alfa; Starting dose and frequency of darbepoetin alfa are based on previous ESA. The dose will be titrated based on the subject's Hb response

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Mean Hb (Hemoglobin) level	From week 30 to 36
Change in hemoglobin level from baseline to the average during the evaluation period	Baseline and week 30 to 36

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Hb level		Baseline and 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
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 30 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 30 to 36
Hb level		Baseline and up to 52 weeks
Proportion of subjects whose mean hemoglobin levels are in the target range during the evaluation period		From week 30 to 36
Proportion of subjects whose mean hemoglobin levels are above the target range during the evaluation period		From week 30 to 36
Proportion of subjects whose mean hemoglobin levels are below the target range during the evaluation period		From week 30 to 36
Proportion of subjects whose hemoglobin levels are in the target range		Up to 52 weeks
Proportion of subjects whose hemoglobin levels are above the target range		Up to 52 weeks
Proportion of subjects whose hemoglobin levels are below the target range		Up to 52 weeks
Maximum concentration (Cmax) of Molidustat		At baseline, week 12, week 24 and week 52
Area under the concentration-time curve (AUC) of Molidustat		At baseline, week 12, week 24 and week 52
EPO (Erythropoietin) serum concentration of Molidustat		At baseline, week 12, 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.
• Yamamoto H, Taguchi M, Matsuda Y, Iekushi K, Yamada T, Akizawa T. Molidustat for the treatment of renal anaemia in patients with non-dialysis-dependent chronic kidney disease: design and rationale of two phase III studies. BMJ Open. 2019 Jun 14;9(6):e026704. doi: 10.1136/bmjopen-2018-026704.

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): December 13, 2017
• Primary Completion (Actual): July 5, 2019
• Study Completion (Actual): November 28, 2019

Study Registration Dates

• First Submitted: November 19, 2017
• First Submitted That Met QC Criteria: November 19, 2017
• First Posted (Actual): November 22, 2017

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

• Keywords: Renal anemia
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Hematologic Diseases; Renal Insufficiency, Chronic; Renal Insufficiency; Anemia; Hematinics; Darbepoetin alfa
• Other Study ID Numbers: 19350

Drug and device information, study documents

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