Clinical trial NCT03543657: Maintenance Treatment of Renal Anemia in Dialysis Subjects
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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Anemia
Renal Insufficiency, Chronic
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2018-06-01
Enrollment: 229
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 comparison to darbepoetin alfa in dialysis subjects with renal anemia who are treated with Erythropoiesis-Stimulating Agents (ESAs).


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

Primary outcomes:
measure: The mean Hb level during the evaluation period
timeFrame: From week 33 to 36
measure: The change in mean Hb level during the evaluation period from baseline
timeFrame: Baseline and week 33 to 36
Secondary outcomes:
measure: Responder rate: proportion of responders among the subjects
timeFrame: From week 33 to 36
measure: Proportion of subjects who meet each component of the response
timeFrame: From week 33 to 36
measure: Hb level
timeFrame: Up to 52 weeks
measure: Change in 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 33 to 36
measure: Proportion of subjects whose mean hemoglobin level is above the target range
timeFrame: From week 33 to 36
measure: Proportion of subjects whose mean hemoglobin level is below the target range
timeFrame: From week 33 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 8, week 24 and week 52
measure: Area under the concentration-time curve (AUC)
timeFrame: At baseline, week 8, week 24 and week 52
measure: EPO (Erythropoietin) serum concentration
timeFrame: At baseline, week 8, week 24 and week 52
Other outcomes:
Locations:
city: Nagoya
country: Japan
facility: Hakuyoukai Medical corporation Hakuyoukai Hospital
state: Aichi
city: Kashiwa
country: Japan
facility: Shinkashiwa Clinic
state: Chiba
city: Kisarazu
country: Japan
facility: Kisarazu Clinic
state: Chiba
city: Niihama
country: Japan
facility: Kuwajima Clinic
state: Ehime
city: Sabae
country: Japan
facility: Sabae kidney Clinic
state: Fukui
city: Kasuya-gun
country: Japan
facility: Houshikai Kano hospital
state: Fukuoka
city: Kitakyushu
country: Japan
facility: Saiseikai Yahata General Hospital
state: Fukuoka
city: Midori
country: Japan
facility: Sanshikai Toho Hospital
state: Gunma
city: Asahikawa
country: Japan
facility: Asahikawa-Kosei General Hospital
state: Hokkaido
city: Chitose
country: Japan
facility: Koizumi Cardiology Medical Clinic
state: Hokkaido
city: Ishikari
country: Japan
facility: Ishikari Hospital
state: Hokkaido
city: Noboribetsu
country: Japan
facility: Itami Kidney Clinic
state: Hokkaido
city: Sapporo
country: Japan
facility: Souen Central Hospital
state: Hokkaido
city: Kasama
country: Japan
facility: Ibaraki Prefectural Central Hospital
state: Ibaraki
city: Koga
country: Japan
facility: Japanese Red Cross Koga Hospital
state: Ibaraki
city: Mito
country: Japan
facility: Mito Kyodo General Hospital
state: Ibaraki
city: Totte
country: Japan
facility: Tokiwa Clinic
state: Ibaraki
city: Tsuchiura
country: Japan
facility: Tsuchiura Beryl Clinic
state: Ibaraki
city: Tsukuba
country: Japan
facility: Kikuchi Medical Clinic
state: Ibaraki
city: Hakusan
country: Japan
facility: Public Central Hospital of Matto Ishikawa
state: Ishikawa
city: Sakaide
country: Japan
facility: Kaisei Hospital
state: Kagawa
city: Atsugi
country: Japan
facility: Honatsugi Medical Clinic
state: Kanagawa
city: Chigasaki
country: Japan
facility: Chigasaki Central Clinic
state: Kanagawa
city: Sagamihara
country: Japan
facility: Toshiba Rinkan Hospital
state: Kanagawa
city: Yokohama
country: Japan
facility: Yokohama Jin Clinic
state: Kanagawa
city: Yokohama
country: Japan
facility: Eda Clinic
state: Kanagawa
city: Yokohama
country: Japan
facility: Kaminagaya Saitou Clinic
state: Kanagawa
city: Kurokawa-gun
country: Japan
facility: Seisuikai Yoshioka Mahoroba Clinic
state: Miyagi
city: Osaki
country: Japan
facility: Eijinkai Hospital
state: Miyagi
city: Iida
country: Japan
facility: Iida Hospital
state: Nagano
city: Matsumoto
country: Japan
facility: Kanno Dialysis & Vascular Access Clinic
state: Nagano
city: Matsumoto
country: Japan
facility: Matsumoto City Hospital
state: Nagano
city: Ueda
country: Japan
facility: Maruko Central Hospital
state: Nagano
city: Hirakata
country: Japan
facility: Arisawa General Hospital
state: Osaka
city: Toyonaka
country: Japan
facility: Toyonaka Keijinkai Clinic
state: Osaka
city: Hanyu
country: Japan
facility: Hanyu General Hospital
state: Saitama
city: Higashimatsuyama
country: Japan
facility: Higashimatsuyamakohjin Clinic
state: Saitama
city: Koshigaya
country: Japan
facility: Saiyu Clinic
state: Saitama
city: Toda
country: Japan
facility: Todachuo General Hospital
state: Saitama
city: Hachioji
country: Japan
facility: Hachioji Azumacho Clinic
state: Tokyo
city: Kodaira
country: Japan
facility: Kodaira Kitaguchi Clinic
state: Tokyo
city: Ube
country: Japan
facility: Saint Hill Hospital
state: Yamaguchi
city: Chiba
country: Japan
facility: Medical corporation association Shunshin-kai Inage hospital
city: Fukuoka
country: Japan
facility: Ikeda Vascular Access Nephrology Dialysis
city: Fukuoka
country: Japan
facility: Oohashi internal medicine circulatory Clinic
city: Kumamoto
country: Japan
facility: Ueki Imafuji Clinic
city: Nagano
country: Japan
facility: Medical Corporation Suzukihinyoukika
city: Nagasaki
country: Japan
facility: Nagasaki Kidney Hospital
city: Osaka
country: Japan
facility: Akagaki Clinic
city: Osaka
country: Japan
facility: Nishi Shinryosho
city: Osaka
country: Japan
facility: Chibune Clinic
city: Saitama
country: Japan
facility: Iwatsuki-minami Hospital
city: Yamagata
country: Japan
facility: Yamagata Tokushukai 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: 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.