Clinical trial NCT02021409: Maintenance Treatment of Anemia in Pre-dialysis Subjects With Chronic Kidney Disease on Darbepoetin 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 (Darbepoetin Alfa) in the Maintenance Treatment of Anemia in Pre-dialysis Subjects With Chronic Kidney Disease on Darbepoetin Treatment in Europe and Asia Pacific
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Anemia
Renal Insufficiency, Chronic
Keywords: Anemia on CKD
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2013-12-27
Enrollment: 126
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: Anaemia is a condition in which blood has a lower than normal number of red blood cells. It can also occur if red blood cells do not contain enough haemoglobin, an oxygen carrying part of blood. Anaemia is common in patients with chronic kidney disease. Healthy kidneys produce a hormone called erythropoietin, which stimulates the bone marrow to produce the proper number of red blood cells needed to carry oxygen to vital organs. Chronic kidney disease is a general term that means that the kidneys are not functioning to their full potential. The study drug, BAY85-3934, is being evaluated as a drug to increase the body's ability to produce erythropoietin.

The purpose of this study is to find out if the study drug, a tablet taken orally, is safe and effective for the treatment of anaemia associated with chronic kidney disease.

The study will enroll 120 patients at multiple locations in Europe, Asia and Australia. Participation will involve a screening visit and between 12 and 15 study visits scheduled over a period of approximately 5 to 7 months. The estimated total duration of study treatment will be 16 weeks. During these scheduled visits patients will undergo a number of procedures to confirm efficacy and safety of the study drug, including measurement of heart rate and blood pressure, physical examination, Electrocardiogram and blood/urine sample collection for laboratory tests.

The study will be conducted at 3 hospitals in the UK. Bayer HealthCare AG is funding this research.


Eligibility criteria: Inclusion Criteria:

* Male or female subjects ≥ 18 years of age with anemia of chronic kidney disease (CKD) at screening
* Estimated glomerular filtration rate (eGFR) of \< 60 mL/min/1.73 m2 (Modification of Diet in Renal Disease or the formula according to Matsuo, et al.)
* Not on dialysis and not expected to begin dialysis during the treatment period of the study (at least 16 weeks from randomization)
* Treated with darbepoetin via intravenous (IV) or subcutaneous (SC) route with a weekly, bi-weekly, or monthly dose, having had no more than one dose change within 8 weeks prior to randomization
* At least one kidney
* Mean screening hemoglobin (Hb) concentration of 10.0 to 12.0 g/dL
* Men who agree to use adequate contraception when sexually active or women without childbearing potential

Exclusion Criteria:

* Subjects with significant acute or chronic bleeding, such as overt gastrointestinal bleeding
* Active hemolysis or diagnosis of hemolytic syndrome
* History of myelodysplastic syndrome, multiple myeloma, marrow fibrosis, or pure red-cell aplasia (PRCA)
* History of hemosiderosis or hemochromatosis
* Hereditary hemoglobinopathies (such as sickle cell disease and thalassemia major)
* Aplastic anemia
* Chronic lymphoproliferative diseases
* Proliferative choroidal or retinal disease, such as neovascular age-related macular degeneration or proliferative diabetic retinopathy that is likely to require invasive treatment (intraocular injections or laser photocoagulation) during the study
* Chronic inflammatory disease that could impact erythropoiesis (e.g., systemic lupus erythematosis, rheumatoid arthritis, celiac disease) even if it is currently in remission
* Known hypersensitivity to the study drugs (active substances or excipients of the preparations)
* Uncontrolled and symptomatic hyperparathyroidism
* Uncontrolled active infection
* Previous or concurrent cancer except cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors (Ta, Tis, and T1) or any cancer curatively treated \> 3 years prior to randomization
* 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)

Primary outcomes:
measure: Change in local laboratory hemoglobin level from baseline to the average during the last 4 weeks treatment period
timeFrame: Baseline and week 12 to 16
Secondary outcomes:
measure: Maintenance in hemoglobin target range (10.0 to 12.0 g/dL)
timeFrame: Up to 16 weeks
measure: Change in hemoglobin level
timeFrame: Baseline up to 16 weeks
measure: Number of patients with hemoglobin levels outside the target range
timeFrame: Week 12 to 16
measure: Dose level in the evaluation period
timeFrame: Week 12 to 16
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: Gosford
country: Australia
state: New South Wales
city: Reservoir
country: Australia
state: Victoria
city: Dobrich
country: Bulgaria
city: Lovech
country: Bulgaria
city: Montana
country: Bulgaria
city: Pazardjik
country: Bulgaria
city: Sofia
country: Bulgaria
city: Stara Zagora
country: Bulgaria
city: Grenoble Cedex 9
country: France
city: Pierre Benite Cedex
country: France
city: Bonn
country: Germany
state: Nordrhein-Westfalen
city: Baja
country: Hungary
city: Budapest
country: Hungary
city: Esztergom
country: Hungary
city: Kaposvar
country: Hungary
city: Pecs
country: Hungary
city: Szigetvar
country: Hungary
city: Ashkelon
country: Israel
city: Hadera
country: Israel
city: Kfar Saba
country: Israel
city: Nahariya
country: Israel
city: Napoli
country: Italy
state: Campania
city: Brescia
country: Italy
state: Lombardia
city: Cremona
country: Italy
state: Lombardia
city: Lecco
country: Italy
state: Lombardia
city: Pavia
country: Italy
state: Lombardia
city: Livorno
country: Italy
state: Toscana
city: Kitakyushu
country: Japan
state: Fukuoka
city: Okawa
country: Japan
state: Fukuoka
city: Muroran
country: Japan
state: Hokkaido
city: Morioka
country: Japan
state: Iwate
city: Fujisawa
country: Japan
state: Kanagawa
city: Kuwana
country: Japan
state: Mie
city: Chiba
country: Japan
city: Fukuoka
country: Japan
city: Nagano
country: Japan
city: Bucheon-si
country: Korea, Republic of
state: Gyeonggido
city: Bialystok
country: Poland
city: Radom
country: Poland
city: Bucharest
country: Romania
city: Bucharest
country: Romania
city: Oradea
country: Romania
city: Targu-Mures
country: Romania
city: L'Hospitalet de Llobregat
country: Spain
state: Barcelona
city: San Sebastián de los Reyes
country: Spain
state: Madrid
city: Madrid
country: Spain
city: Ankara
country: Turkey
facility: Ankara Univ. Medical Faculty
city: Ankara
country: Turkey
facility: Baskent University Medical Faculty
city: Izmir
country: Turkey
facility: Sifa University Medical Faculty
city: Cambridge
country: United Kingdom
state: Cambridgeshire
city: Liverpool
country: United Kingdom
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.