Clinical trial NCT03350321: A Study of Molidustat for Correction of Renal Anemia in Non-dialysis Subjects
Official title: 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 With Renal Anemia Who Are Not Treated With Erythropoiesis-Stimulating Agents (ESAs)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Anemia
Renal Insufficiency, Chronic
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2017-11-22
Enrollment: 162
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the efficacy and safety of molidustat in non-dialysis subjects with renal anemia who are not treated with Erythropoiesis-Stimulating Agents (ESAs).


Eligibility criteria: Inclusion Criteria:

* Subjects with estimated glomerular filtration rate (eGFR)\< 60 mL/min/1.73m\^2 (Chronic kidney disease \[CKD\] stages 3 to 5)
* 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
* Not treated with ESAs and/or HIF-PH inhibitors within 8 weeks prior to randomization
* Mean of the last 2 central laboratory Hb levels during the screening period must be ≥ 8.0 and \< 11.0 g/dL (2 measurements must be taken ≥ 2 days apart and the difference between the 2 measurements must be \< 1.2 g/dL) and the last measurements must be taken within 14 days prior to randomization
* Ferritin ≥ 50 ng/mL 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 and poorly controlled arterial hypertension (defined as systolic BP≥ 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)

Primary outcomes:
measure: Mean Hb (Hemoglobin) level
timeFrame: From week 30 to 36
measure: Change in hemoglobin level from baseline to the average during the evaluation period
timeFrame: Baseline and week 30 to 36
Secondary outcomes:
measure: Responder rate: proportion of responders among the subjects
timeFrame: From week 30 to 36
measure: Rate of rise in Hb (Hemoglobin) level (g/dL/week)
timeFrame: Up to 8 weeks
measure: Rate of rise in Hb (Hemoglobin) level (g/dL/week)
timeFrame: Up to 4 weeks
measure: Proportion of subjects who meet each component of the response
timeFrame: From week 30 to 36
measure: Cumulative proportion of subjects who achieve the lower limit of the target Hb range at least once
timeFrame: Up to 52 weeks
measure: Change in Hb level
timeFrame: Baseline and up to 52 weeks
measure: Hb level
timeFrame: Baseline and up to 52 weeks
measure: Proportion of subjects whose mean hemoglobin level is in the target range
timeFrame: From week 30 to 36
measure: Proportion of subjects whose mean hemoglobin level is above the target range
timeFrame: From week 30 to 36
measure: Proportion of subjects whose mean hemoglobin level is below the target range
timeFrame: From week 30 to 36
measure: Proportion of subjects with hemoglobin levels in the target range
timeFrame: Up to 52 weeks
measure: Proportion of subjects with hemoglobin levels above the target range
timeFrame: Up to 52 weeks
measure: Proportion of subjects with hemoglobin levels below the target range
timeFrame: Up to 52 weeks
measure: Proportion of subjects whose maximum rise in Hb between each consecutive visits is above 0.5 g/dL/week
timeFrame: Up to 52 weeks
measure: Number of participants with serious adverse events
timeFrame: Up to 52 weeks
measure: Maximum concentration (Cmax)
timeFrame: At baseline, week 12, week 24 and week 52
measure: Area under the concentration-time curve (AUC)
timeFrame: At baseline, week 12, week 24 and week 52
measure: EPO (Erythropoietin) serum concentration
timeFrame: At baseline, week 12, week 24 and week 52
Other outcomes:
Locations:
city: Yatomi
country: Japan
facility: Kainan Hospital
state: Aichi
city: Matsudo
country: Japan
facility: Seikeikai New Tokyo Heart Clinic
state: Chiba
city: Matsuyama
country: Japan
facility: Ehime Prefectural Central Hospital
state: Ehime
city: Matsuyama
country: Japan
facility: Saiseikai Matsuyama Hospital
state: Ehime
city: Iizuka
country: Japan
facility: Iizuka Hospital
state: Fukuoka
city: Kitakyushu
country: Japan
facility: Kokura Memorial Hospital
state: Fukuoka
city: Kitakyushu
country: Japan
facility: Steel Memorial Yawata Hospital
state: Fukuoka
city: Koga
country: Japan
facility: National Fukuoka-Higashi Medical Center
state: Fukuoka
city: Kurume
country: Japan
facility: Kurume University Hospital
state: Fukuoka
city: Kurume
country: Japan
facility: St.Mary's Hospital
state: Fukuoka
city: Hashima-gun
country: Japan
facility: Matsunami Health Promotion Clinic
state: Gifu
city: Tajimi
country: Japan
facility: Gifu Prefectural Tajimi Hospital
state: Gifu
city: Aki-gun
country: Japan
facility: Mazda Hospital of Mazda Motor Corporation
state: Hiroshima
city: Fukuyama
country: Japan
facility: Nippon Kokan Fukuyama Hospital
state: Hiroshima
city: Sapporo
country: Japan
facility: Teine Keijinkai Clinic
state: Hokkaido
city: Kobe
country: Japan
facility: Kobe City Medical Center General Hospital
state: Hyogo
city: Kobe
country: Japan
facility: National Hospital Organization Kobe Medical Center
state: Hyogo
city: Higashiibaraki
country: Japan
facility: National hospital Organization Mito Medical Center
state: Ibaraki
city: Mito
country: Japan
facility: Mito Kyodo General Hospital
state: Ibaraki
city: Takamatsu
country: Japan
facility: KenAiKai medical corporation Akiyama clinic
state: Kagawa
city: Kanoya
country: Japan
facility: Ikeda Hospital
state: Kagoshima
city: Fujisawa
country: Japan
facility: Fujisawa City Hospital
state: Kanagawa
city: Kawasaki
country: Japan
facility: Koukan Clinic
state: Kanagawa
city: Yokohama
country: Japan
facility: Showa University Fujigaoka Hospital
state: Kanagawa
city: Yokosuka
country: Japan
facility: Yokosuka Kyosai Hospital
state: Kanagawa
city: Arao
country: Japan
facility: Arao Municipal Hospital
state: Kumamoto
city: Yatsushiro
country: Japan
facility: Kumamoto Rosai Hospital
state: Kumamoto
city: Uji
country: Japan
facility: Uji-Tokushukai Medical Center
state: Kyoto
city: Yokkaichi
country: Japan
facility: JCHO Yokkaichi Hazu Medical Center
state: Mie
city: Ishinomaki
country: Japan
facility: Japanese Red Cross Ishinomaki Hospital
state: Miyagi
city: Komoro
country: Japan
facility: Asama Nanroku Komoro Medical Center
state: Nagano
city: Shibata
country: Japan
facility: Niigata Prefectural Shibata Hospital
state: Niigata
city: Uruma
country: Japan
facility: Okinawa prefectural Chubu Hospital
state: Okinawa
city: Suita
country: Japan
facility: Osaka Saiseikai Senri Hospital
state: Osaka
city: Tondabayashi
country: Japan
facility: Osaka Pref. Saiseikai Tondabayashi Hospital
state: Osaka
city: Kitamoto
country: Japan
facility: Kitasato University Medical Center
state: Saitama
city: Iwata
country: Japan
facility: Iwata City Hospital
state: Shizuoka
city: Itabashi-ku
country: Japan
facility: Toshima Hospital
state: Tokyo
city: Itabashi-ku
country: Japan
facility: Nihon University Itabashi Hospital
state: Tokyo
city: Koto-ku
country: Japan
facility: Showa University Koto Toyosu Hospital
state: Tokyo
city: Meguro-ku
country: Japan
facility: National Hospital Organization Tokyo Medical Center
state: Tokyo
city: Chuo
country: Japan
facility: University of Yamanashi Hospital
state: Yamanashi
city: Fukui
country: Japan
facility: Fukui Prefectural Hospital
city: Fukuoka
country: Japan
facility: National Hospital Organization Kyushu Medical Center
city: Fukuoka
country: Japan
facility: Kyushu University Hospital
city: Fukuoka
country: Japan
facility: Fukuoka University Hospital
city: Fukushima
country: Japan
facility: Fukushima Medical University Hospital
city: Gifu
country: Japan
facility: Asahi University Hospital
city: Kochi
country: Japan
facility: National Hospital Organization Kochi National Hospital
city: Nara
country: Japan
facility: Nara Prefecture General Medical Center
city: Oita
country: Japan
facility: Japanese Red Cross Oita Hospital
city: Osaka
country: Japan
facility: Kitano Hospital
city: Osaka
country: Japan
facility: National Hospital Organization Osaka National Hospital
city: Osaka
country: Japan
facility: Osaka Red Cross Hospital
city: Osaka
country: Japan
facility: Nippon Life Hospital
city: Osaka
country: Japan
facility: Chibune Clinic
city: Osaka
country: Japan
facility: Osaka General Medical Center
city: Osaka
country: Japan
facility: Social Corporation Keigakukai Minamiosaka Hospital
city: Shizuoka
country: Japan
facility: Shizuoka Saiseikai General Hospital
city: Shizuoka
country: Japan
facility: Suruga Clinic
city: Wakayama
country: Japan
facility: Wakayama Medical University Hospital
Study officials:
References:
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.
citation: 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.