Anemia in chronic kidney disease patients with dialysis MedDRA version: 20.0 Level: PT Classification code 10064848 Term: Chronic kidney disease System Organ Class: 10038359 - Renal and urinary disorders
Conditions
Interventions
Product Name: roxadustat
Product Code: AZD9941
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: roxadustat
CAS Number: 808118-40-3
Current Sponsor code: AZD9941
Concentration unit: mg mill
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 at screening visit 1 3. Previous versions of the protocol prior to US amendment ver 6.0 and outside of US amendment ver 7.0: - Receiving or initiating hemodialysis or peritoneal dialysis for treatment of native kidney end-stage renal disease (ESRD) at least 30 days prior to visit 1. Patients treated with hemodialysis must have access consisting of an arteriovenous fistula, AV graft, or tunneled (permanent) catheter. Patients on peritoneal dialysis must have a functioning peritoneal dialysis catheter in place. Starting with US amendment ver. 6.0 and outside of US amendment ver 7.0 (changed to recruit incident dialysis patients only): - Receiving or initiating hemodialysis or peritoneal dialysis for treatment of native kidney end-stage renal disease (ESRD) for a minimum of 2 weeks and a maximum of 4 months prior to randomization. Patients treated with hemodialysis must have access consisting of an arteriovenous fistula, AV graft, or tunneled (permanent) catheter. Patients on peritoneal dialysis must have a functioning peritoneal dialysis catheter in place. 4. Two central laboratory Hb values during the screening period, obtained at least 7 days apart, must be =65 years) yes F.1.3.1 Number of subjects for this age range 450
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 randomisation in the present study 3. New York Heart Association Class III or IV congestive heart failure at enrolment 4. Myocardial infarction, acute coronary syndrome, stroke, seizure or a thrombotic/thromboembolic event (e.g., deep vein thrombosis or pulmonary embolism) within 12 weeks prior to randomization 5. History of chronic liver disease (e.g., chronic infectious hepatitis, chronic auto-immune liver disease, cirrhosis or fibrosis of the liver) 6. 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 7. Known and untreated retinal vein occlusion or known and untreated proliferative diabetic retinopathy (risk for retinal vein thrombosis) 8. 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. CT scan or MRI) conducted at screening or within 12 weeks prior to randomization. 9. Uncontrolled hypertension at the time of randomization (defined as systolic BP =180 mmHg or diastolic BP =100 mmHg on repeated measurement post-dialysis in hemodialysis patients or at any time in peritoneal dialysis patients), contraindication to epoetin alfa treatment (e.g., pure red cell aplasia, hypersensitivity or know inability to tolerate epoetin alfa) 10. History of prostate cancer, breast 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. 11. Positive for any of the following: human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or anti-hepatitis C virus antibody (anti-HCV Ab) 12. Chronic inflammatory diseases such as rheumatoid arthritis, SLE, ankylosing spondylitis, psoriatic arthritis or inflammatory bowel disease that is determined to be the principal cause of anemia 13. Known hemosiderosis, hemochromatosis or hypercoagulable condition 14. Any prior organ transplant with the exception of an autologous renal transplant or a renal transplant that was subsequently removed ("explanted") or scheduled organ transplantation date 15. Any red blood cell (RBC) transfusion during the screening period 16. Any current condition leading to active significant blood loss 17. Any prior treatment with roxadustat or a hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) 18. 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 the month preceding the first administration of IP in this study. (Note: patients consented and screened, but not randomized in this study or a previous study are not excluded) 19. History of alcohol or drug abuse within 2 years prior to randomization 20. Females of childbearing potential, unless using contraception as detailed in the protocol or sexual abstinence (see Section 3.8) 21. Pregnant or breastfeeding females 22. Known allergy to the investigational product or any of its ingredients 23. Any medical condition, including active, clinically significant infection, that in the opinion of the investigator or Sponsor may pose a
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: Secondary Efficacy Objectives: - The efficacy of roxadustat as compared to epoetin alfa based on Hb response and level during the study - The effect of roxadustat on Low-density lipoprotein (LDL) cholesterol as compared to epoetin alfa - The efficacy of roxadustat based on Hb response in inflamed subjects - The need for IV iron use in subjects treated with roxadustat as compared to epoetin alfa - The need for RBC transfusion as rescue therapy in subjects treated with roxadustat as compared to epoetin alfa Secondary Safety Objectives: - To evaluate the safety and tolerability of roxadustat.;Primary end point(s): Primary Efficacy Endpoint: - US FDA: Mean change from baseline in Hb averaged over week 28 to week 52. - EU health authorities: The EU (EMA) primary efficacy endpoint is change in Hb from BL to the average level during the evaluation period (defined as week 28 until week 36), without having received rescue therapy (i.e. RBC transfusion for all subjects or ESA for subjects treated with roxadustat) within 6 weeks prior to and during this 8-week evaluation period. Primary Safety Endpoint: Adjudicated CV safety data. Analyses of the adjudicated events are described in a separate pooled statistical analysis plan.;Timepoint(s) of evaluation of this end point: Primary Efficacy Endpoint: - US FDA: From week 28 to week 52. - EU health authorities: From week 28 to week 36. Primary Safety Endpoint: Analyses of the adjudicated events are described in a separate pooled statistical analysis plan.;Main Objective: Primary Efficacy Objective: Evaluate the efficacy of Roxadustat for the treatment of anemia in CKD subjects on dialysis. Primary Safety Objective: Contribute CV safety data to pooled safety analyses across the phase 3 program | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary Efficacy Endpoints: 1. The EU primary endpoint is the first secondary efficacy endpoint for FDA. 2. Mean change from baseline in LDL cholesterol from baseline to week 24 3. 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) 4. Proportion of total time of Hb = 10 g/dL from week 28 to week 52. 5. Proportion of total time of Hb within the interval of 10-12 g/dL from week 28 to week 52 6. Average monthly IV iron use 7. Time-to-first (and proportion of subjects receiving) administration of red blood cell (RBC) transfusion as rescue therapy 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 week 28 to week 36. 2. From randomization to week 24. 3. From week 28 to week 52. 4. From week 28 to week 52. 5. From week 28 to week 52. 6. From week 36 to End of Study (EOS). 7. From the first date of study drug (SD) intake to EOS for subjects without SD discontinuation (SDD) or to the last SD intake for SDD subjects. Safety Endpoints: From date of first dose of SD to 28 days after last dose of SD. | — |
Countries
Argentina, Australia, Brazil, Bulgaria, Canada, Czech Republic, Hungary, India, Mexico, Peru, Philippines, Poland, Romania, Russian Federation, Slovakia, Spain, Sweden, Thailand, Ukraine, United States, Vietnam
Contacts
Public ContactInformation Centre
AstraZeneca AB
Outcome results
None listed