Clinical trial NCT01975818: Maintenance Treatment of Anemia Associated With Chronic Kidney Disease (CKD) in Hemodialysis Subjects on Epoetin Alfa / Beta Treatment Versus BAY85-3934
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Anemia
Renal Insufficiency, Chronic
Keywords: Anemia of CKD on dialysis
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2013-11-05
Enrollment: 201
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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


Eligibility criteria: 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

Primary outcomes:
measure: Change in local laboratory hemoglobin level from baseline to the average during the last 4 weeks treatment period
timeFrame: Baseline and weeks 14 to 17
Secondary outcomes:
measure: Mean of the hemoglobin (Hb) levels in the target range (10.0 to 11.0 g/dL)
timeFrame: From week 14 to 17
measure: Mean of the hemoglobin levels in the target range (9.5 to 11.5 g/dL)
timeFrame: From week 14 to 17
measure: Change from baseline in Hb during active treatment
timeFrame: Baseline and weeks 14 to 17
measure: Number of patients with hemoglobin levels outside the target range
timeFrame: From week 14 to 17
measure: Dose level in the evaluation period
timeFrame: Up to 16 weeks
measure: Duration of exposure on each dose level
timeFrame: Up to 16 weeks
measure: Number of subjects requiring titration of dose
timeFrame: Up to 16 weeks
measure: Number of participants with serious adverse events as a measure of safety and tolerability
timeFrame: Up to 16 weeks
Other outcomes:
Locations:
city: Azusa
country: United States
state: California
city: Long Beach
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Lynwood
country: United States
state: California
city: Northridge
country: United States
state: California
city: San Dimas
country: United States
state: California
city: Whittier
country: United States
state: California
city: Whittier
country: United States
state: California
city: New Port Richey
country: United States
state: Florida
city: Pembroke Pines
country: United States
state: Florida
city: Detroit
country: United States
state: Michigan
city: Detroit
country: United States
state: Michigan
city: Creve Coeur
country: United States
state: Missouri
city: Eatontown
country: United States
state: New Jersey
city: Brooklyn
country: United States
state: New York
city: Buffalo
country: United States
state: New York
city: Fresh Meadows
country: United States
state: New York
city: Cincinnati
country: United States
state: Ohio
city: Toledo
country: United States
state: Ohio
city: Oklahoma City
country: United States
state: Oklahoma
city: Nashville
country: United States
state: Tennessee
city: Fort Worth
country: United States
state: Texas
city: Fort Worth
country: United States
state: Texas
city: Fort Worth
country: United States
state: Texas
city: Grand Prairie
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Mansfield
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Muroran
country: Japan
state: Hokkaido
city: Himeji
country: Japan
state: Hyogo
city: Kuwana
country: Japan
state: Mie
city: Kyoto
country: Japan
city: Nagano
country: Japan
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
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.