Clinical trial NCT03351166: A Study of Molidustat for Correction of Renal Anemia in Dialysis Subjects
Official title: A Single Arm, Multicenter Study to Investigate the Efficacy and Safety of Oral Molidustat in 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: 25
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


Eligibility criteria: Inclusion Criteria:

* Subject with end-stage kidney disease (ESKD) on dialysis (including, hemodiafiltration, hemodialysis, and other modalities except for peritoneal dialysis) weekly or more than weekly
* Body weight \> 40 and ≤ 160 kg at screening
* Male or female subject ≥ 20 years of age at screening
* At least one kidney
* Not treated with ESAs and/or HIF-PH inhibitors within 8 weeks prior to randomization. However, in case of the patient washed out from ESAs, when the mean Hb (at least 2 central laboratory measurements must be taken ≥ 2 days apart before dialysis) has decrease to ≥ 0.5 dL from the Hb level (central laboratory measurement, before dialysis) after the last ESA administration, AND the interval from the last ESA administration to the study drug assignment was over 1 week for epoetin-alpha, 2 weeks for darbepoetin alpha or 4 weeks for epoetin beta pegol
* Mean of the last 2 Hb level (central laboratory measurement, before dialysis) during the screening period must be ≥ 8.0 and \< 10.0 g/dL (2 measurements must be taken ≥ 2 days apart and the difference between the 2 measurements must be \< 1.2 g/dL) with the last screening Hb measurement within 14 days prior to study drug assignment
* 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: Rate of rise in Hb (Hemoglobin) level (g/dL/week)
timeFrame: Up to 8 weeks
measure: Responder rate: proportion of responders among the subjects
timeFrame: Week 21 to 24
Secondary outcomes:
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: Week 21 to 24
measure: Cumulative proportion of subjects who achieve the lower limit of the target Hb range at least once at each visit
timeFrame: Up to 24 weeks
measure: Hb level
timeFrame: Baseline and up to 24 weeks
measure: Change in Hb level
timeFrame: Baseline and up to 24 weeks
measure: Proportion of subjects whose mean hemoglobin levels are above the target range during the evaluation period
timeFrame: Week 21 to 24
measure: Proportion of subjects whose mean hemoglobin levels are below the target range during the evaluation period
timeFrame: Week 21 to 24
measure: Proportion of subjects whose mean hemoglobin levels are in the target range during the evaluation period
timeFrame: Week 21 to 24
measure: Proportion of subjects with hemoglobin levels above the target range
timeFrame: Up to 24 weeks
measure: Proportion of subjects with hemoglobin levels below the target range
timeFrame: Up to 24 weeks
measure: Proportion of subjects with hemoglobin levels in the target range
timeFrame: Up to 24 weeks
measure: Proportion of subjects whose maximum rise in Hb between each consecutive visits is above 0.5 g/dL/week
timeFrame: Up to 24 weeks
measure: Number of participants with serious adverse events
timeFrame: Up to 24 weeks
measure: Maximum concentration (Cmax) of Molidustat
timeFrame: Baseline, Week 8, Week16 and Week 24
measure: Area under the concentration-time curve (AUC) of Molidustat
timeFrame: Baseline, Week 8, Week16 and Week 24
measure: EPO (Erythropoietin) serum concentration of Molidustat
timeFrame: Baseline, Week 8, Week16 and Week 24
Other outcomes:
Locations:
city: Kasuya-gun
country: Japan
facility: Houshikai Kano hospital
state: Fukuoka
city: Hashima-gun
country: Japan
facility: Matsunami General Hospital
state: Gifu
city: Asahikawa
country: Japan
facility: Asahikawa-Kosei General Hospital
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: Takasago
country: Japan
facility: Takasago Seibu Hospital
state: Hyogo
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: Ishinomaki
country: Japan
facility: Japanese Red Cross Ishinomaki Hospital
state: Miyagi
city: Iida
country: Japan
facility: Iida Hospital
state: Nagano
city: Toyonaka
country: Japan
facility: Toyonaka Keijinkai Clinic
state: Osaka
city: Kodaira
country: Japan
facility: Kodaira Kitaguchi Clinic
state: Tokyo
city: Chiba
country: Japan
facility: Medical corporation association Shunshin-kai Inage hospital
city: Fukuoka
country: Japan
facility: Fukuoka Renal Clinic
city: Saitama
country: Japan
facility: Ohmiya Chuo General Hospital
city: Yamagata
country: Japan
facility: Yamagata Tokushukai Hospital
Study officials:
References:
citation: Akizawa T, Nobori K, Matsuda Y, Hayashi Y, Hayasaki T, Yamamoto H. Molidustat for anemia correction in Japanese patients undergoing hemodialysis: a single-arm, phase 3 study. Ther Apher Dial. 2021 Dec;25(6):917-925. doi: 10.1111/1744-9987.13627. Epub 2021 Mar 22.
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.