Anemia in chronic kidney disease patients without dialysis. MedDRA version: 20.0 Level: LLT Classification code 10076410 Term: Chronic kidney disease stage 3 System Organ Class: 100000004857 MedDRA version: 20.0 Level: LLT Classification code 10076411 Term: Chronic kidney disease stage 4 System Organ Class: 100000004857
Conditions
Interventions
Product Code: AZD9941
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Roxadustat
CAS Number: 808118-40-3
Current Sponsor co
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Provision of informed consent prior to any study specific procedures 2) Age =18 years. 3) A glomerular filtration rate (eGFR) =65 years) yes F.1.3.1 Number of subjects for this age range 1300
Exclusion criteria
Exclusion criteria: 1) Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site) 2) Previous randomization in the present study 3) Any erythropoietin analogue treatment within 6 weeks of randomization. 4) New York Heart Association Class III or IV congestive heart failure at enrollment 5) Myocardial infarction (MI), acute coronary syndrome, stroke, seizure or a thrombotic/thromboembolic event (e.g., deep vein thrombosis or pulmonary embolism) within 12 weeks prior to randomization 6) History of chronic liver disease (e.g., chronic infectious hepatitis, chronic autoimmune liver disease, cirrhosis or fibrosis of the liver) 7) Known hereditary hematologic disease such as thalassemia, sickle cell anemia, a history of pure red cell aplasia or other known causes for anemia other than CKD. 8) Known and untreated retinal vein occlusion or known and untreated proliferative diabetic retinopathy (risk for retinal vein thrombosis). 9) Diagnosis or suspicion (e.g. complex kidney cyst of Bosniak Category IIF, III or IV) of renal cell carcinoma on renal ultrasound (or other imaging procedure e.g. computerized tomography scan or magnetic resonance Imaging conducted at screening or within 12 weeks prior to randomization. 10) Systolic blood pressure (BP) =160 mmHg or diastolic BP =95 mmHg, within 2 weeks prior to randomization. Patients may be rescreened once BP controlled. 11) History of prostate cancer, reast cancer or any other malignancy, except the following: Cancers determined to be cured or in remission for =5 years, curatively resected basal cell or squamous cell skin cancers, cervical cancer in situ, or resected colonic polyps. 12) Positive for any of the following: human immunodeficiency virus, hepatitis B surface antigen or anti hepatitis C virus antibody. 13) Chronic inflammatory diseases such as rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, psoriatic Arthritis or inflammatory bowel disease that is determined to be the principal cause of anemia. 14) Known hemosiderosis, hemochromatosis or hypercoagulable condition 15) Any prior organ transplant or a scheduled organ transplantation date 16) Any red blood cell transfusion (RBC) during the screening period 17) Any current condition leading to active significant blood loss. 18) Any treatment with roxadustat or a hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI). 19) Has received another new chemical entity (defined as a compound which has not been approved for marketing) or has participated in any other clinical study that included drug treatment within at least 1 month of the first administration of investigation product in this study. (Note: patients consented and screened, but not randomized in this study or a previous study are not excluded). 20) History of alcohol or drug abuse within 2 years prior to randomization. 21) Females of childbearing potential, unless using contraception as detailed in the protocol or sexual abstinence. 22) Pregnant or breastfeeding females. 23) Known allergy to the investigational product or
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary Efficacy Objective: Evaluate the efficacy of roxadustat compared to placebo for the treatment of anemia in CKD subjects not on dialysis. Primary Safety Objective: Contribute CV safety data to pooled Safety analyses across the phase 3 program ; Secondary Objective: Secondary Efficacy Objectives: - The efficacy of roxadustat compared to placebo based on Hb response and level during the study - The efficacy of roxadustat compared to placebo based on Hb response in inflamed subjects - The effect of roxadustat compared to placebo on Low-density lipoprotein (LDL) cholesterol - The need for rescue therapy in subjects treated with roxadustat as compared to placebo - The effect of roxadustat on anemia symptoms and health-related quality of life (HRQoL) based on comparison with placebo - The effect on the CKD Progression of roxadustat as compared to placebo Secondary Safety Objectives: - To evaluate the safety and tolerability of roxadustat. ; Primary end point(s): Primary Efficacy Endpoint: US FDA: The primary efficacy endpoint for the US is the mean Change from baseline in Hb averaged over week 28 to week 52. EU health authorities: The primary efficacy endpoint is whether patients achieved Hb Response (Yes/No) where Yes is defined as: o Hb = 11.0 g/dL and Hb increase from baseline by = 1.0 g/dL, for subjects with baseline Hb > 8.0 g/dL; or o Hb increase from baseline by = 2.0 g/dL, for subjects with baseline Hb = 8.0 g/dL at two consecutive visits [dates] (with available data) separated at least 5 days during the first 24 weeks of treatment without having received rescue therapy (RBC transfusion, ESA, or IV iron) prior to Hb response. Prima | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary Efficacy Endpoints: 1) Hb response as noted for EU Primary Endpoint. 2) Mean change in Hb from baseline to the subjects mean level between week 28 to week 52 in subjects with baseline high-sensitivity C-reactive protein (hsCRP) greater than the Upper Limit Normal (ULN) 3) Proportion of total time of Hb = 10 g/dL from week 28 to week 52. 4) Proportion of total time of Hb within the interval of 10-12 g/dL from week 28 to week 52 5) Mean change in LDL cholesterol from baseline to week 24 6) Time-to-first (and proportion of subjects receiving) instance of receiving intravenous (IV) iron, red blood cell (RBC) transfusions, or erythropoietin analogue as rescue therapy. 7) Time-to-first (and proportion of subjects receiving) instance of receiving red blood cell (RBC) transfusions as rescue therapy. 8) Change from baseline in SF-36 Vitality (VT) sub-score 9) Annual rate of eGFR change in log scale, calculated as the linear slope of log (eGFR values) to prior to initiation of dialysis/kidney transplant 10) Change from baseline in SF-36 Physical Functioning (PF) sub-score Secondary Safety Endpoints: Adverse events (AEs), serious adverse events (SAEs). Changes in vital signs, electrocardiogram (ECG) and laboratory values. ; Timepoint(s) of evaluation of this end point: Efficacy Endpoints: 1) From randomization to week 24 2) From week 28 to week 52 3) From week 28 to week 52 4) From week 28 to week 52 5) From randomization to week 24 6) From the first date of study drug (SD) intake to EOS for subjects without SD discontinuation (SDD) or to the last date plus 28 days of SD intake for SDD subjects | — |
Countries
Argentina, Brazil, Bulgaria, Canada, Czech Republic, Germany, Hungary, India, Italy, Korea, Republic of, Mexico, Peru, Philippines, Poland, Romania, Russian Federation, Slovakia, Spain, Taiwan, Thailand, Turkey, Ukraine, United Kingdom, United States, Vietnam
Contacts
Public ContactInformation Centre
AstraZeneca AB
Outcome results
None listed