Maintenance Treatment of Anemia Associated With Chronic Kidney Disease (CKD) in Hemodialysis Subjects on Epoetin Alfa / Beta Treatment Versus BAY85-3934 (DIALOGUE4)

A Randomized, Parallel Group, Open-label, Multicenter Study to Investigate the Efficacy and Safety of Oral BAY85-3934 and Active Comparator (Epoetin Alfa / Beta) in the Maintenance Treatment of Subjects With Anemia Associated With Chronic Kidney Disease Who Are on Dialysis and on Treatment With an Erythropoiesis-stimulating Agent in the United States and Japan

Evaluate efficacy and safety of 16 weeks of titrated dose treatment with BAY85-3934 versus epoetin alfa/beta as measured by hemoglobin (Hb) levels. Fixed starting doses of 25, 50,75 and 150 mg of BAY85-3934 titrated at the scheduled dose control visits. Titration will be based on the subject's Hb response and tolerability of the prior dose. Planned doses include 15, 25, 50, 75, 100,150 and 200 mg/day

Study Overview

• Status: Completed
• Conditions: Renal Insufficiency, Chronic; Anemia
• Intervention / Treatment: Drug: Molidustat (BAY 85-3934); Biological: Epoetin alfa/beta

• Study Type: Interventional
• Enrollment (Actual): 201
• Phase: Phase 2

Contacts and Locations

Study Locations

• Japan
  • Kyoto, Japan, 607-8116
  • Nagano, Japan, 388-8004
  • Hokkaido
    • Muroran, Hokkaido, Japan, 050-0083
  • Hyogo
    • Himeji, Hyogo, Japan, 670-0947
  • Mie
    • Kuwana, Mie, Japan, 511-0061
• United States
  • California
    • Azusa, California, United States, 91702
    • Long Beach, California, United States, 90813
    • Los Angeles, California, United States, 90025
    • Lynwood, California, United States, 90262
    • Northridge, California, United States, 91324
    • San Dimas, California, United States, 91773
    • Whittier, California, United States, 90606
    • Whittier, California, United States, 90602
  • Florida
    • New Port Richey, Florida, United States, 34652
    • Pembroke Pines, Florida, United States, 33028
  • Michigan
    • Detroit, Michigan, United States, 48236
    • Detroit, Michigan, United States, 48202
  • Missouri
    • Creve Coeur, Missouri, United States, 63141
  • New Jersey
    • Eatontown, New Jersey, United States, 07724
  • New York
    • Brooklyn, New York, United States, 11212
    • Buffalo, New York, United States, 14215
    • Fresh Meadows, New York, United States, 11365
  • Ohio
    • Cincinnati, Ohio, United States, 45206
    • Toledo, Ohio, United States, 43615
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73116
  • Tennessee
    • Nashville, Tennessee, United States, 37212-8150
  • Texas
    • Fort Worth, Texas, United States, 76104
    • Fort Worth, Texas, United States, 76105
    • Fort Worth, Texas, United States, 76164
    • Grand Prairie, Texas, United States, 75050
    • Houston, Texas, United States, 77004
    • Houston, Texas, United States, 77091
    • Mansfield, Texas, United States, 76063
    • San Antonio, Texas, United States, 78229
    • San Antonio, Texas, United States, 78215

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:

• - Eligible subjects will have a diagnosis of anemia associated with CKD(chronic kidney disease).
• Women without childbearing potential
• Male or female subject ≥ 18 years of age with anemia of CKD at screening
• On dialysis, defined as regular long-term hemodialysis, with the same modality of dialysis for ≥ 3 months before randomization
• Dialysis vascular access via native arteriovenous fistula, synthetic graft, long-term catheters, or long-term tunneled catheters
• Treated with epoetin alfa (US or Japan) or epoetin beta (Japan) via intravenous (IV) or subcutaneous (SC) route, on stable dosing defined as a < 50% change from the maximum prescribed weekly dose with no change in the prescribed frequency during the last 8 weeks prior to randomization
• At least one kidney
• Mean screening Hb concentration 9.0 to 11.5 g/dL inclusive (mean of all local laboratory Hb measurements [at least 2 measurements must be taken ≥ 2 days apart] during the 4 week screening period, AND none of the measurements can be < 9.0 g/dL or > 12.0 g /dL
• Serum ferritin levels ≥ 100 μg/L OR transferrin saturation ≥ 20% at screening. Iron substitution is allowed
• Folate and vitamin B12 levels above the lower limit of normal. Supplementation is allowed
• Exclusion Criteria:
• Subjects with significant acute or chronic bleeding, such as overt gastrointestinal bleeding
• Hereditary hemoglobinopathies (including, but not limited to, sickle cell disease, beta thalassemia, and thalassemia major) which may be the primary cause of anemia
• Chronic lymphoproliferative diseases
• Any allograft (including renal allograft) in place and on immunosuppressive therapy, or a scheduled kidney transplant within the next 16 weeks (being on a waiting list does not exclude the subject)
• Chronic inflammatory disease that could impact erythropoiesis (e.g., systemic lupus erythematosis, rheumatoid arthritis, celiac disease)
• Subjects treated with immuno- or myelosuppressive therapy within 8 weeks prior to randomization: e.g., everolimus, sirolimus, rituximab, azathioprine, mycophenolate mofetil, mycophenolic acid, cyclosporine,methotrexate, and tacrolimus, chemotherapeutic agents and other anticancer agents, and systemic steroids (except inhaled steroids) for 7 days
• RBC-containing transfusion within 8 weeks before randomization
• History of cardio- (cerebro-) vascular events (e.g., unstable angina, myocardial infarction, stroke, transient ischemic attack, deep vein thrombosis, pulmonary embolism) within the last 6 months from the initial screening visit
• Sustained, poorly controlled arterial hypertension or hypotension at screening, defined as a mean BP ≥ 180/110 mmHg or systolic BP < 95 mmHg, respectively
• Severe rhythm or conduction disorder (e.g., HR < 50 or > 110 bpm, atrial flutter, prolonged QT >500 msec, second or third degree atrioventricular [AV]block if not treated with a pacemaker)
• New York Heart Association Class III or IV congestive heart failure
• Severe hepatic insufficiency (defined as alanine aminotransferase [ALT], aspartate aminotransferase [AST], or gamma-glutamyl transferase > 3 times the upper limit of normal [ULN], total bilirubin > 2 mg/dL, or Child-Pugh B or C) or active hepatitis in the investigator's opinion
• A scheduled surgery that may be expected to lead to significant blood loss

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

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Molidustat (BAY 85-3934)(25mg); Starting dose of 25 mg of BAY85-3934 as once-daily oral tablets. Regular titrations at dose control visits. Titration occuring every 4-weeks will be based on the subject's Hb response and tolerability of the prior dose. Total treatment time is 16 weeks. Planned doses include 15, 25, 50, 75, 100,150 and 200 mg once daily.	Drug: Molidustat (BAY 85-3934); Oral doses of BAY85-3934 will be available in multiples of 25,50,75 and 150 mg tablets
Experimental: Molidustat (BAY 85-3934)(50mg); Starting dose of 50 mg of BAY85-3934 as once-daily oral tablets. Regular titrations at dose control visits Titration occuring every 4-weeks will be based on the subject's Hb response and tolerability of the prior dose. Total treatment time is 16 weeks. Planned doses include 15, 25, 50, 75, 100,150 and 200 mg once daily.	Drug: Molidustat (BAY 85-3934); Oral doses of BAY85-3934 will be available in multiples of 25,50,75 and 150 mg tablets
Experimental: Molidustat (BAY 85-3934) (75mg); Starting dose of 75 mg of BAY85-3934 as once-daily oral tablets. Regular titrations at dose control visits Titration occuring every 4-weeks will be based on the subject's Hb response and tolerability of the prior dose. Total treatment time is 16 weeks. Planned doses include 15, 25, 50, 75, 100,150 and 200 mg once daily.,	Drug: Molidustat (BAY 85-3934); Oral doses of BAY85-3934 will be available in multiples of 25,50,75 and 150 mg tablets
Experimental: Molidustat (BAY 85-3934) (150mg); Starting dose of 150 mg of BAY85-3934 as once-daily oral tablets. Regular titrations at dose control visits Titration occuring every 4-weeks will be based on the subject's Hb response and tolerability of the prior dose. Total treatment time is 16 weeks. Planned doses include 15, 25, 50, 75, 100, 150 and 200 mg once daily	Drug: Molidustat (BAY 85-3934); Oral doses of BAY85-3934 will be available in multiples of 25,50,75 and 150 mg tablets
Active Comparator: Epoetin alfa/beta; Starting dose at the subject's current weekly dose. Administered IV or SC 3 times per week. Doses will be titrated at the scheduled dose control visits according to the local label. Titration will be based on the subject's Hb response and tolerability of the prior dose. Epoetin alfa may be administered in either the United States (US) or Japan; epoetin beta will only be administered in Japan.	Biological: Epoetin alfa/beta

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in local laboratory hemoglobin level from baseline to the average during the last 4 weeks treatment period	Baseline and weeks 14 to 17

Secondary Outcome Measures

Outcome Measure	Time Frame
Duration of exposure on each dose level	Up to 16 weeks
Number of subjects requiring titration of dose	Up to 16 weeks
Number of participants with serious adverse events as a measure of safety and tolerability	Up to 16 weeks
Mean of the hemoglobin (Hb) levels in the target range (10.0 to 11.0 g/dL)	From week 14 to 17
Mean of the hemoglobin levels in the target range (9.5 to 11.5 g/dL)	From week 14 to 17
Change from baseline in Hb during active treatment	Baseline and weeks 14 to 17
Number of patients with hemoglobin levels outside the target range	From week 14 to 17
Dose level in the evaluation period	Up to 16 weeks

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.

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): October 28, 2013
• Primary Completion (Actual): October 23, 2015
• Study Completion (Actual): December 15, 2015

Study Registration Dates

• First Submitted: October 18, 2013
• First Submitted That Met QC Criteria: October 29, 2013
• First Posted (Estimate): November 5, 2013

Study Record Updates

• Last Update Posted (Actual): September 20, 2019
• Last Update Submitted That Met QC Criteria: September 17, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: Anemia of CKD on dialysis
• Additional Relevant MeSH Terms: Urologic Diseases; Hematologic Diseases; Kidney Diseases; Renal Insufficiency, Chronic; Renal Insufficiency; Anemia; Hematinics; Epoetin Alfa
• Other Study ID Numbers: 16208